Antimicrobials

J Pharmacobiodyn, 1982 Dec, 5(12), 941 - 50
Mode of protective action of fosfomycin against dibekacin-induced nephrotoxicity in the dehydrated rats; Inouye S et al.; We studied the mechanism on protective effect of fosfomycin against experimental nephrotoxicity induced by dibekacin . In order to simplify an experimental model, the dehydrated Wistar rats were used, because a single injection of dibekacin at 30 mg/kg induced acute renal failure in the dehydrated rats, characterized by alteration of urinalytic parameters and BUN values, and retarded elimination of dibekacin from blood . When the rats were administered simultaneously with fosfomycin at 120 mg/kg, the rate of elimination was restored almost to normal, accompanied with improvement of the nephrotoxic parameters . However, markedly accelerated elimination over normal one was not observed, indicating that the improved elimination was not the reason of protection but a result of normal kidney function . On the other hand, fosfomycin protected the proximal tubular lysosomes from the injury of aminoglycoside, as evidenced a) in vivo by suppression of myeloid body formation and protection of lysosomal membrane integrity of the rats treated with dibekacin, and b) in vitro by dose-dependent protection of the lysosomal membrane integrity of the kidney cells . A study of structure-protective activity relation revealed that phosphonate anion possessing an epoxy function was important for protection, and that the mechanism of protection differed from the antibacterial mechanism.

J Antibiot (Tokyo), 1982 Dec, 35(12), 1692 - 9
Phospholipid bilayer permeability of beta-lactam antibiotics; Yamaguchi A et al.; Liposomes containing penicillinase or cephalosporinase were prepared from the phospholipids of Escherichia coli . After free beta-lactamase was inactivated by clavulanic acid or penicillanic acid sulfone followed by separation of inactivated enzyme and inhibitor from liposomes by gel filtration, the permeability of these liposomes to ampicillin, cefazolin and cephaloridine was estimated by measuring the hydrolysis of these antibiotics by the entrapped enzymes . The permeability parameter C (minute-1 microM lipid-1) of ampicillin, cefazolin and cephaloridine was calculated to be 2.35 X 10(-4), 0.33 X 10(-4) and 0.52 X 10(-4), respectively . The lipid bilayer permeability of these antibiotics was also measured by using the liposomes containing these antibiotics . About half of the initially entrapped ampicillin was released from the liposomes within 80 minutes, while no significant release of cefazolin and cephaloridine could be detected during the same period . These results clearly indicates that the lipid bilayer membrane is more permeable to ampicillin than cefazolin and cephaloridine, and they are consistent with the observations of Sawai et al., who showed that ampicillin was a more effective antibacterial drug than cefazolin and cephaloridine against the porin-deficient mutants.

J Clin Microbiol, 1982 Dec, 16(6), 1003 - 6
Disk diffusion testing with polymyxin and amikacin for differentiation of Mycobacterium fortuitum and Mycobacterium chelonei; Wallace RJ Jr et al.; Disk diffusion is one method of susceptibility testing of the Mycobacterium fortuitum complex to antibacterial agents . We utilized disks of polymyxin B (300 U), amikacin, and kanamycin to determine whether they could also be used for species identification when compared with standard biochemical methods . With the polymyxin disk, 100% of 75 M . fortuitum strains produced zones of inhibition, whereas none (0%) of 58 Mycobacterium chelonei subspecies abscessus and chelonei strains had any zone of inhibition . With the amikacin disk, 99% of M . fortuitum biovariant fortuitum had zones of greater than or equal to 30 mm compared with 6% of M . chelonei . The rare M . chelonei-like organisms gave variable results, and 42% of the unnamed "third group" biovariant of M . fortuitum exhibited an unusual but diagnostic pattern of small zone sizes to amikacin and no zone to kanamycin . The kanamycin disk was otherwise not helpful, although it resulted in larger zone sizes for M . chelonei than did amikacin . Thus, disk diffusion susceptibilities which include these disks (especially polymyxin) will provide presumptive evidence of species as well as susceptibility data.

Nouv Presse Med, 1982 Nov 18, 11(46), 3439 - 43
{Dibekacin in the treatment of septicemia}; Becq-Giraudon B et al.; During an open multicentric trial (17 centers), we have treated 62 septicemia by dibekacin, alone or associated with other antibacterial drugs . Taking into account the degree of severity of these patients, the results are considered satisfactory in 47 patients . 15 failures were noted (including 9 deaths) . General and local tolerance were good, in spite of the duration of treatment.

Ann Immunol (Paris), 1982 Nov-Dec, 133D(3), 235 - 44
Cellular pharmacokinetics of spiramycin in cultured macrophages; Zenebergh A et al.; To gain a better understanding of the antibacterial and antiprotozoal activity of spiramycin as well as the characteristic conditions of cellular defence, we studied its accumulation and intracellular localization in cultured macrophages . Within two hours spiramycin in its active form is accumulated intracellularly by macrophages to a concentration 10 to 20 times that found in the extracellular medium; it is released slowly by the cells when they are incubated in antibiotic-free medium . After differential or isopycnic centrifugation, a bimodal localization of spiramycin was found; one part could be associated with the soluble cytosolic fraction and another with organelles sedimenting at a density of 1.17 g/ml, which represent part of the lysosomal population and perhaps the phagosomes.

J Antibiot (Tokyo), 1982 Nov, 35(11), 1507 - 12
1-N-acylation of gentamicin C1a by a cyclic, chiral gamma-amino-alpha-hydroxy acid related to the (S)-4-amino-2-hydroxybutyric acid; Philippe M et al.; A semisynthetic aminoglycoside antibiotic 15, containing a cyclic gamma-amino-alpha-hydroxy acid, related to the 1-N-4-amino-2-hydroxybutyric acid (AHBA) side chain of butirosins and amikacin, has been prepared . Conveniently protected 3,2',6'-tris-N-tert-butoxycarbonylgentamicin C1a (12) was condensed with the phtalimido active ester 10 to give after catalytic reduction and deprotection, the hitherto unknown 1-N-substituted gentamicin C1a 15 . The requisite side chain was synthesized from the readily available D-(-)-quinic acid . The antibacterial properties of 15 are given.

An Esp Pediatr, 1982 Nov, 17(5), 383 - 9
{Logical use of prophylactic antibacterial agents in infectious post-appendectomy complications . A controlled clinical trial}; Abdel-Lah BA et al.; A prospective clinical trial is carried out in 88 patients undergoing surgery for removal of the appendix . Authors show the efficacy of the association of pre and postoperative gentamycin plus clindamycin or lincomycin in prevention of postoperative infections, which, in the cases with non-ruptured appendix was 0%, and in gangrenous or perforated cases was 8.6%, with a global infection rate of 6% in this prophylactic subgroup I . However, when the same antibiotics are administered only postoperatively (subgroup II), global infection rate is of 34.2% similar to data in the literature in which no antibiotics were given . There have been no complications derived from this antibiotic prophylaxis.

Rev Infect Dis, 1982 Nov-Dec, 4 Suppl, S496 - 500
Moxalactam: the first of a new class of beta-lactam antibiotics; Webber JA et al.; Moxalactam is the first member of a new class of beta-lactam antibiotics to be evaluated clinically . Although structurally related to cephalosporins, moxalactam has an oxygen atom where the cephalosporin nucleus has a sulfur atom . The substitution of oxygen for sulfur in moxalactam provides it with greater antibacterial activity than that of its cephalosporin analog . Moxalactam has three other structural elements that affect biologic activity: the methyltetrazolethio moiety, which maximizes in vitro activity; the 7-alpha-methoxy substituent, which confers beta-lactamase stability; and the p-hydroxyphenylmalonyl group, which positively influences not only beta-lactamase stability and the antibacterial spectrum of moxalactam, but also its pharmacokinetics, and leads to a long half-life without high serum binding.

Arch Sci Med (Torino), 1982 Oct-Dec, 139(4), 491 - 7
{Antibacterial activity of disinfectant solutions containing quaternary ammonium compounds for the storage of surgical instruments}; Riolo U et al.; A survey conducted among the health managements and dispensary services of all Italian hospitals showed that disinfectants containing quaternary ammonium salts were most commonly used for the disinfection and storage of surgical instruments (66% of frequencies) . It was therefore decided to run in vitro tests on the bactericidal activity of some of the more frequently used substances containing one or more of these salts as their active principle . Five were therefore examined against 8 hospital and 4 lab strains, namely three aqueous solution: 1% benzalkonium chloride plus 1% ethylbenzalkonium chloride; 0.6% alkyldimethylbenzylammonium chloride, plus 0.185% diisobutylphenoxyethoxyethylbenzyl ammonium chloride monohdydrate and 0.133% diisobutylcresoxyethoxydimethylbenzyl ammonium chloride monohydrate; 0.1% dodecylbenzylammonium-N-diethyl alcohol chloride; and two alcoholic solutions: 0.1% alkyldimethylbenzylammonium chloride; 0.25% benzalkonium chloride (F.U.).

Antibiotiki, 1982 Oct, 27(10), 784 - 7
{Leukergic reaction in viral hepatitis to antibacterial preparations}; Andreichin MA et al.; Forty-one patients with virus hepatitis were examined . The leukergic reactions were determined with the agglomeration test with the use of benzylpenicillin, levomycetin, erythromycin, sulfadimesine, furazolidone and some pathogenic agents, such as nicodine, oxaphenamide, lipamide, methacyl . The control group consisted of 10 healthy persons . During the acute stage of the disease the positive tests with the use of the antibacterial drugs ranged from 31.6 to 47.2 per cent, while during the period of reconvalescence they amounted to 0-20 per cent . The frequency of leukergia to the antibacterial drugs also depended on the severity of the disease . The leukergic reactions to the pathogenic agents were observed rarely even among the healthy persons.

Am J Hosp Pharm, 1982 Oct, 39(10), 1678 - 80
Prophylactic use of restricted antibacterials in Czechoslovakia; Grunt J et al.; The prophylactic use of restricted antibacterials in Czechoslovakia was studied . Data from 10 hospitals were collected for approximately 10,000 therapeutic applications of eight restricted antibacterials to 8411 patients . The drugs monitored were oxacillin, kanamycin, gentamicin, carbenicillin, co-trimoxazole, colistin, cephalosporins, and lincomycin/clindamycin . Within one year in the 10 hospitals studied, 943 of 8411 patients (11.2%) received one of the restricted antibacterials for prophylaxis . In the newborn ward, 61.7% of all restricted antibacterial therapy was for prophylaxis; in the gynecology and obstetrics ward, 32.2% . Approximately 14% of patients receiving restricted antibacterials for prophylaxis received two or more, and many of them received nonrestricted antibacterials concurrently . Duration of therapy with these drugs averaged 7.9 days, and 10% of these courses of therapy exceeded 11 days . Although the selection of individual restricted antibacterials for prophylaxis was generally satisfactory, irrational prolongation of therapy was not, indicating that use of these drugs must be supervised carefully.

Farmaco {Sci}, 1982 Oct, 37(10), 701 - 10
{Structure-activity relationships in N1-acetylderivatives of sulpha drugs.}; Vampa G et al.; The N1-acetylderivatives (ASA) of sulphanylamides (SA) were prepared and their stability to hydrolysis was evaluated together with the spectroscopic and antibacteric activity parameters, with the aim both of obtaining electronic structure-activity relationships and of comparing these results with those previously found for SA . From our results it appears that: a) the stability to hydrolysis is dramatically reduced on passing from the aqueous medium (pH 7) to the culture broth, and that b) in general, the ASA examined do not show any greater antibacterial activity with respect to the parent compounds, as suggested by the values of the spectroscopic indices-taken as experimental electronic indices . This result is in full agreement with the structure-activity relationships previously proposed fo the sulpha drugs.

Hum Pathol, 1982 Oct, 13(10), 934 - 9
The nephropathy of cystic fibrosis: a human model of chronic nephrotoxicity; Abramowsky CR et al.; Patients with cystic fibrosis are chronically exposed to several potentially nephrotoxic factors . These include bacterial infections with their associated immune complexes and the antibiotics (aminoglycosides) used in their treatment . In addition, diabetes mellitus, liver disease, and cor pulmonale, commonly seen in these patients, may produce renal injury . To assess the extent of this injury, we performed morphologic and immunopathologic studies of the kidneys of 34 patients at autopsy . The group included 23 female and 11 male patients; their ages ranged from 4 months to 35 years and their disease was diagnosed one month to 22 years prior to death . The histological changes included glomerulomegaly, a mesangiopathic lesion, and tubulointerstitial disease frequently associated with acute and chronic tubular injury . The last was characterized by abundant tubular lysosomal proliferation and tubular atrophy suggestive of chronic amino-glycoside injury . Diagnostic diabetic lesions were not seen . Immunofluorescence studies predominantly revealed deposits of IgM or C3, or both, in glomeruli and arterioles in 18 patients . Although an anti-Pseudomonas antiserum did not show bacterial antigens in the tissues, elution studies in two specimens demonstrated antibacterial antibodies . These observations, coupled with the finding of ultrastructural glomerular deposits, suggest immune complex-mediated injury . No correlation was found between the severity or type of renal histologic lesion and patient age or duration of cystic fibrosis . Despite the occurrence of renal failure in six patients, renal involvement is currently of limited clinical concern in cystic fibrosis . Nevertheless, continued exposure to bacterial immune complexes and aminoglycosides, among other factors, can result in potentially serious renal disease.

JAMA, 1982 Oct 1, 248(13), 1636 - 7
Sex and spermicides: preventing unintended pregnancy and infection; Cates W Jr et al.; PIP: All contraceptives except the IUD, which promotes development of pelvic inflammatory disease, appear to confer some degree of protection from sexually transmitted diseases (STDs) . Results of a study by Jick and colleagues reported in volume 248 of the Journal of the American Medical Association indicated that women classified as spermicide "users" had gonorrhea rates only 1/4 those of women who used oral contraceptives or had undergone surgical sterilization . Their data also suggest that spermicides may protect against vaginal infections for which metronidazole is prescribed . The authors are cautious in interpreting the data because 2 key risk factors associated with a woman's development of gonorrhea could not be evaluated: differences in sexual behavior between women using spermicides and those using other contraceptives, and the concurrent protection effect of mechanical barrier contraceptives as distinct from the chemical antibacterial action of spermicides . No information was provided on whether women received their spermicide prescriptions specifically for STD prophylaxis, so that the extent of any selection bias could not be measured . Questions might also be raised concerning the data base and methodology used in the study, but the data is consistent with results of previous in vitro investigations and other observational data . If spermicides do provide protection against STDs, there are several possible concerns regarding their widespread promotion as prophylaxis for groups at high risk for both STDs and unintended pregnancy: such agents must be used regularly; their use may simply mask laboratory detection of some STDs without curing the infection; spermicides could be found to have teratogenic health risks; or their use could provide women with a false sense of security . The advantages of spermicides are that they are nonprescription items, less expensive than most contraceptives, under the control of women, and capable of selective use with casual partners . A sophisticated evaluation of possible public health benefits and risks is needed to measure the true effects of spermicides .

Antimicrob Agents Chemother, 1982 Oct, 22(4), 571 - 8
Antibacterial activity and mechanism of action of phosphonopeptides based on aminomethylphosphonic acid; Atherton FR et al.; Phosphonopeptides based on aminomethylphosphonic acid as the C-terminal residue linked to L-amino acids possessed antibacterial activity in vitro and in vivo . Analogs in this series were generally less potent than corresponding compounds based on L-1-aminoethylphosphonic acid such as alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) . Significant differences in antibacterial spectra were observed . The mechanism of action involved active transport of the peptide mimetics into the bacterial cells, followed by intracellular release of high concentrations of aminomethylphosphonic acid which inhibited bacterial cell wall biosynthesis . Aminomethylphosphonic acid behaved as a mimetic of both D- and L-alanine and inhibited D-Ala-D-Ala synthetase (EC 6.3.2.4.), alanine racemase (EC 5.1.1.1.), and UDP-N-acetylmuramyl-L-alanine synthetase (EC 6.3.2.8.) . The minimal inhibitory concentration of L-norvalyl-aminomethylphosphonic acid was essentially unaffected by the presence of D-alanine, whereas the activity of the corresponding L-norvalyl derivative of L-1-aminoethylphosphonic acid was markedly decreased . Substantial differences in the inhibitory and lytic activity of the L-norvalyl derivatives of aminomethylphosphonic and L-1-aminoethylphosphonic acids were also observed when these agents were combined with other inhibitors of bacterial cell wall biosynthesis.

Int J Radiat Biol Relat Stud Phys Chem Med, 1982 Oct, 42(4), 457 - 68
Pulse radiolysis and cellular studies of a new class of radiosensitizers: 2-nitrobenzofurans; Averbeck D et al.; A group of 2-nitrobenzofurans possessing antibacterial and antiparasitic properties have now been shown to be potential radiosensitizers from investigations in simple aqueous solution by pulse radiolysis and from survival studies in yeast . The radical anions of several 2-nitrobenzofurans were formed by the rapid reaction of the parent molecules with hydrated electrons or with various pyrimidine electron adducts . Studies of equilibria between these radical anions, the parent nitrobenzofurans and the corresponding species derived from quinones with known one-electron reduction potentials, showed that the one-electron reduction potentials of all the furans under investigation lie between -285 and -309 mV . They are thus more electron affinic than the nitroimidazoles (misonidazole and metronidazole) currently under clinical evaluation . 5-Hydroxy- and 7-hydroxy-2-nitrobenzofuran were demonstrated to form weak complexes with DNA (binding constant 80 M-1) and strong complexes with HSA (binding constant 10(5)M-1) . In the yeast Saccharomyces cerevisiae the nitrobenzofurans exert radiosensitizing effects on survival either similar to or higher than misonidazole.

Appl Environ Microbiol, 1982 Oct, 44(4), 814 - 9
Effect of antecedent growth conditions on sensitivity of Escherichia coli to chlorine dioxide; Berg JD et al.; Bacterial resistance to inactivation by antibacterial agents that is induced by the growth environment was studied . Escherichia coli was grown in batch culture and in a chemostat, and the following parameters were varied: type of substrate, growth rate, temperature, and cell density during growth . Low doses (0.75 mg/liter) of chlorine dioxide were used to inactivate the cultures . The results demonstrated that populations grown under conditions that more closely approximated natural aquatic environments were more resistant than those grown under commonly employed batch culture conditions . In particular, bacteria grown at submaximal rates were more resistant than their counterparts grown at mumax . The most resistant populations encountered in this study were those grown at D values of 0.02 h-1 and 0.06 h-1 at 25 degrees C . Growth at 15 degrees C led to greater resistance than did growth at 37 degrees C . The conditions that produced relatively resistant phenotypes were much closer to those found in most natural environments than are the typical conditions of batch culture methods . The importance of major physiological changes that can be induced by the antecedent growth environment is discussed in light of the possible modes of action of several disinfectants.

Biochemistry, 1982 Sep 28, 21(20), 5020 - 31
Synthesis of the antibacterial peptide cecropin A (1-33); Merrifield RB et al.; Cecropin A(1-33) was synthesized by an improved stepwise solid-phase method . The synthesis was designed to give high coupling yields and minimal amounts of byproducts . All coupling steps were monitored for completion by a new ninhydrin procedure, and the fully protected peptide-resin was analyzed for deletion peptides by the solid-phase Edman preview technique . Both methods indicated that the average coupling yield was greater than 99.8% . The unpurified peptide mixture resulting from HF cleavage and extraction into 10% acetic acid was analyzed by reverse-phase high-pressure liquid chromatography, and 93% of the total product was shown to be the desired {Trp(For)2}cecropin A(1-33), indicating an average yield per synthetic cycle of 99.8% . Removal of the formyl group at pH 9, followed by ion-exchange chromatography, gave the purified product . Cecropin A(1-33) showed antibacterial activity against both Gram-positive and Gram-negative bacteria . Against Escherichia coli, the activity was only slightly lower than that of the natural 37-residue cecropin A when tested over a 100-fold concentration range; the minimum inhibitory concentration was approximately 1 microM . The formyl derivative was somewhat less effective in killing E . coli than the free 1-33 peptide . The antibacterial activity was discussed in terms of an amphipathic alpha-helix structure and the binding of the peptide to bacterial membranes.

Dtsch Med Wochenschr, 1982 Sep 10, 107(36), 1343 - 6
{Cefotaxim--an alternative in the treatment of purulent meningitis in children?}; Helwig H et al.; Cefotaxim was administered to ten children with purulent meningitis . All isolated micro-organisms were highly sensitive to it in serial dilution, except for one case, and were quickly removed from blood and CSF by the administration of cefotaxim alone . Blood and CSF concentrations measured in eight children were much above the minimal inhibitory concentration for the particular micro-organism . Thus cefotaxim has a high antibacterial activity and satisfactory CSF passage in purulent meningitis caused by sensitive, especially gram-negative, bacteria and is well suitable for therapy, if penicillins alone or combined are not applicable or effective.

Mol Cell Biochem, 1982 Sep 3, 47(2), 115 - 24
The fractionation and characterization of bovine tear proteins, especially lactoferrin; Banyard MR et al.; Gentle procedures are described for the fractionation of bovine tear fluid by a combination of centrifugation, salt precipitation, gel filtration and ion exchange chromatography . Fractions are examined by gel electrophoretic immunological methods . Reference patterns are compiled and compared with bovine milk and serum patterns . Properties of some of th components are determined . Lactoferrin is isolated in two separate, but closely related, fractions . An acidic protein with a molecular weight of 23 000 daltons, is also isolated . Distinct heterogeneity is observed between individual animals, suggestive of a genetic polymorphism . A method is presented for the determination of the antibacterial activity of tear fluid and its fractions.

Med Hypotheses, 1982 Sep, 9(3), 325 - 30
Hypothesis: new concepts on the pathogenesis of early prosthetic valve endocarditis; Leitersdorf E et al.; During the years 1970-1980, 697 patients had valve replacement surgery at our institution . Thirty patients subsequently developed prosthetic valve endocarditis (P.V.E.) . Reexamination of the native valves of 25 of these patients revealed histopathological evidence of thromboendocarditis in 7, 5 of whom subsequently developed early P.V.E . In 3 out of 25 matched controls in whom P.V.E . was not diagnosed clinically, similar pathological findings were found; these patients all had fever pre- or post-operatively and were treated with a short antibacterial course, but no definite clinical diagnosis was made . We suggest that there is a close relationship between subclinical thromboendocarditis on the native valve and the early development of infective endocarditis on the implanted artificial valve.

Eur J Biochem, 1982 Sep, 127(1), 207 - 17
Insect immunity: isolation and structure of cecropin D and four minor antibacterial components from Cecropia pupae; Hultmark D et al.; We have investigated low molecular weight antibacterial proteins from the Cecropia moth . Hyalophora cecropia . In addition to the previously described cecropins A and B, five new antibacterial proteins were discovered, the cecropins C, D, E and F, and the factor G . A scheme for the purification of these factors is presented . Cecropin D is a major cecropin, its amino acid sequence, WNPFKELEKVGQRVRDAVISAGPAVATVAQATALAK, shows homology to cecropin A and B . Like these cecropins, cecropin D has a block C-terminal . The previously tentative C-terminal sequence of cecropin A is also confirmed . It is concluded that the three major cecropins, A, B and D, are products of three different genes that are derived from a common ancestor . The cecropins C, E and F were present in very low amounts, and thus their primary structures could not be fully elucidated . Cecropin C has an amino acid sequence that up to residue 37 is identical to the sequence of A, though it lacks the C-terminal blocking group . It may be a precursor or degradation product of cecropin A . The minor cecropin E shows a similar relation to cecropin D . Cecropin F has a single amino acid replacement (17 Asp leads to Asn) compared to cecropin D, and is probably a product of an allele that is present at a low frequency in the population . The primary structure of the factor G could not be determined, however its amino acid composition is different from that of the cecropins . All the major cecropins were found to be efficient against several gram-positive and gram-negative bacterial strains . No significant difference was found between them in their activity against Escherichia coli, though against some less susceptible bacteria the most basic cecropins were more effective, the activity falling in the series B greater than A much greater than D.

Biofizika, 1982 Sep-Oct, 27(5), 900 - 5
{Optical tactics of antibacterial therapy for the trigger model of the infection process}; Kholodenko BN et al.; A problem is considered on optimal concentration of an antibacterial drug for the model of illness, in which the illness and health states of the host organism are identified with alternative stationary states of pathogenic microbe population . The total toxic effect of the drug and pathogenic microbes is minimized . The optical tactics is shown to depend first of all on the growth pattern of the drug toxic effect with the increase of its concentration . If the function approximating this relationship is arched upwards (small rise of the toxic effect) the maximal tolerable concentration of the drug is the optimal one . In other cases the "typical" optimal tactics is that under which the concentration of the drug in the beginning of treatment rapidly increases up to the maximal tolerable one, is maintained at this level for some time and then monotonously decreases to the end of treatment for a long time.

J Clin Microbiol, 1982 Sep, 16(3), 575 - 6
Brucella suis: an unusual cause of suppurative lymphadenitis in an outpatient; Nadler H et al.; A routine aerobic culture of purulent material from a draining sinus tract of a patient with chronic lymphadenitis yielded growth of a fastidious gram-negative coccobacillus later identified as Brucella suis biotype 1 . The patient responded to administration of antibacterial drugs and surgical drainage.

Fed Proc, 1982 Sep, 41(11), 2824 - 7
Amino acid utilization as influenced by antibacterial and anticoccidial drugs; Baker DH et al.; Utilization of amino acids, sulfur-containing amino acid (SAA) in particular, is little affected by antibiotic and anticoccidial compounds . Coccidiosis (i.e., Eimeria acervulina infection) likewise seems to have little effect on SAA utilization . Copper sulfate, a commonly used antibacterial-antifungal compound (used at levels of 100-250 mg/kg diet), interacts with SAA . Hence, at upper levels of copper ingestion (i.e., 250 mg/kg and higher), copper binds SH compounds such as cysteine and reduced glutathione . Dietary SAA requirements are increased in both chicks and rats by dietary copper levels of 250 or 500 mg/kg . Hepatic copper deposition is enhanced by copper feeding and also by E . acervulina infection . These two effects, moreover, appear to be additive . The organic arsenic compound, roxarsone, interacts with SAA also, but in a different way . Thus, whereas added dietary cysteine partially ameliorates copper toxicity due to the binding of copper by cysteine-SH with subsequent excretion, roxarsone toxicity (i.e., 500 mg/kg diet) is exacerbated by supplemental cysteine.

Proc Natl Acad Sci U S A, 1982 Sep, 79(17), 5392 - 5
Immunological castration of male mice by a totally synthetic vaccine administered in saline; Carelli C et al.; It had been reported that immunological neutralization of the hypothalamic luteinizing hormone-releasing hormone (LH-RH) can be achieved by injection of the synthetic hormone, a decapeptide, linked to a carrier and administered with Freund's complete adjuvant . Data presented here demonstrate that the resulting immunological castration can be obtained by administering in an aqueous medium the synthetic decapeptide directly conjugated to the synthetic immunomodulator glycopeptide N-acetylmuramyl-L-alanyl-D-isoglutamine . In the group receiving the conjugate, a higher titer of anti-LH-RH antibodies was obtained than in the group receiving LH-RH in Freund's emulsion . Moreover, histological examination showed that seminiferous tubules were atrophied and that no spermatozoides could be observed . This procedure could lead to applications in the veterinary field and also serve as a useful model for other antiviral or antibacterial synthetic vaccines.

Jpn J Antibiot, 1982 Sep, 35(9), 2200 - 5
{Fundamental and clinical studies of piperacillin in the field of obstetrics and gynecology}; Ohtsuka T et al.; We conducted experimental and clinical tests on piperacillin (PIPC), a drug with a broad antibacterial spectrum, and achieved the following results . PIPC exhibited the following rather high therapeutic blood concentrations: 30--60 micrograms/ml at 1 hour after intravenous injection of 1 g of PIPC, 10 micrograms/ml at 2 hours after intravenous injection of 2 g of PIPC, 7.2 micrograms/ml at 1 1/2 hours after the completion of 1 hour dripping infusion of 1 g of PIPC, and 5.6 micrograms/ml up to 4 hours after the completion of 2 hours dripping infusion of 2 g of PIPC . The yield to the various uterine tissues is presented in decreasing order: the highest yield to ovary was about 40--50% of the blood level, followed by the uterine cervical region, portio vaginalis, myometrium and oviduct, the lowest yield, about 25--30% of the blood level was found in endometrium . We conducted a clinical test on 7 patients with infections of the sexual organs and it proved to be excellent in 3, good in 3, and ineffective in 1 case so that the overall efficacy rate was 85.7% . The patient in whom PIPC proved ineffective suffered from an underlying disease, namely the end stage of cervical cancer . One patient suffered from a slight headache but whether this side effect was due to administration of the drug is not clear . Absolutely no abnormal findings during laboratory tests which could be attributed to drug administration were made . Based on the above results, PIPC was judged to be an extremely useful drug in the treatment of infections in the obstetric and gynecological fields.

J Antibiot (Tokyo), 1982 Sep, 35(9), 1148 - 55
New polyenic antibiotics active against gram-positive and -negative bacteria . II . Screening of antibiotic producers and taxonomical properties of Gluconobacter sp . W-315; Watanabe T et al.; Antibiotic producing bacteria were selected using a new screening method . Eight strains of antibiotic producing bacteria, which required a spent medium of fungi for antibiotic production, were isolated . One of them, a potent producer of antibacterial antibiotic, designated strain W-315, had following taxonomical characteristics; aerobic, Gram-negative, rod shaped and polar flagellated . Furthermore, the organism could grow under acidic conditions (pH 4.5) and had a GC content of 64.4 mole per cent . We concluded that the strain W-315 belonged to Gluconobacter sp . When this bacterium was inoculated into Czapek-Dox medium, bacterial growth and antibiotic production did not occur . The antibiotic production was also not observed even when poor growth was observed in Czapek-Dox medium supplemented with ammonium sulfate . The nutritional requirements for the antibiotic production were also discussed.

J Antibiot (Tokyo), 1982 Aug, 35(8), 979 - 84
Tetrocarcins E1, E2, F and F-1, new antibiotics . Fermentation, isolation and characterization; Tamaoki T et al.; New components of tetrocarcins (E1, E2, F and F-1) were found in the culture broth of Micromonospora chalcea KY 11091 that was known to produce tetrocarcins A, B and C . Tetrocarcin F-1 consisted of tetronolide and nitro sugar (tetronitrose) . Tetrocarcins E1 and E2 consisted of F-1 and deoxy sugar (L-digitoxose) . Tetrocarcin F consisted of F-1 and two deoxy sugars (their structures were not yet determined) . They all showed antibacterial activities against Gram-positive bacteria and the specific activity decreased with decrease in the numbers of deoxy sugars attached to the aglycone.

J Pharm Sci, 1982 Aug, 71(8), 861 - 4
An in vitro model for the study of antibacterial dosage regimen design; Toothaker RD et al.; A model was developed that is capable of simulating antibacterial agent concentration versus time profiles commonly observed following intravenous and intramuscular bolus injections, intravenous infusions, and oral doses, administered as single or multiple doses . The model consisted of two physical compartments separated by a membrane of a commercial hemodialyzer . The 1.08 m2 membrane surface area allowed rapid transmembrane passage of drugs and other small molecules, while membrane pore size prevented bacterial passage . These characteristics allowed bacteria in one of the two compartments of the model to be exposed to time-variant drug concentrations without affecting the number or concentration of bacteria . The model was used to study the effects of a multiple intravenous bolus dosage regimen of ampicillin on Escherichia coli ATCC 12407.

Jpn J Antibiot, 1982 Aug, 35(8), 1945 - 50
{Clinical evaluation of effectiveness of cefmetazole in bone and joint infections in the orthopedic field}; Yamane S et al.; 1 . Cefmetazole (CMZ) was administered to a total number of 12 patients, 10 having acute or chronic osteomyelitis and 2 pyarthrosis in the orthopedic field . The efficacy rate was 91.7% . 2 . Patients received an intravenous instillation of 1 to 2 g CMZ daily for an average period of 29.8 days . 3 . Causative organisms were identified in 8 of the cases examined . In 7 cases S . aureus was isolated . CMZ showed an extremely strong antibacterial activity against S . aureus in a disk test in support of its excellent clinical results . 4 . No abnormality was found with respect to subjective and objective symptoms and in laboratory tests . 5 . The above results and migration of CMZ into the bone tissue at a high concentration suggest that CMZ is an effective and safe drug for bone and joint infection in the orthopedic field.

JAMA, 1982 Jul 23, 248(4), 459 - 64
Mastoid development in ancient and modern populations . A longitudinal radiological study; Gregg JB et al.; The effect of otitis media on the human mastoid process in a common milieu over a millennium was evaluated by comparing two present and four ancient populations . Temporal bone pneumatization patterns indicate that otitis media and mastoiditis existed in antiquity, and there were more altered pneumatization patterns in skulls from the era following European contact than from eras before European contact . Pneumatization patterns were similar in ancient skulls and in a preponderantly white male population mostly born before antibacterial availability . Both ancient and modern pre-antibacterial era temporal bones show more effect of otitis media during childhood than is found in present day schoolchildren . Reasons for differences are explored . It is inferred that upper respiratory tract infections were prevalent in the Upper Missouri River Basin during the past millennium . Furthermore, microbiological agents with virulence similar to today's flora were prevalent in this region more than 1,000 years ago.

Klin Wochenschr, 1982 Jul 15, 60(14), 740 - 2
Interferons and bacterial infections; Kirchner H et al.; Viruses have been established initially as interferon inducers and interferons have been considered to be antiviral proteins only . By our article we wish to draw attention to two observations: a) bacteria and derivatives thereof also are inducing the production of interferon b) interferons activate a number of defense mechanisms that are of potential relevance in antibacterial resistance . These two observations are not new . However, we believe, they deserve renewed attention within the framework of the pleiotropism of interferon effects and of the complexity of antibacterial defense mechanisms.

Biochemistry, 1982 Jul 6, 21(14), 3343 - 52
Antitumor proteins of Streptomyces macromomyceticus: purification and characterization of auromomycin, macromomycin A, and macromomycin D; Vandre DD et al.; Macromomycin A and the two related proteins auromomycin and macromomycin D were isolated from the culture filtrates of Streptomyces macromomyceticus by chromatography on columns of DEAE-cellulose, Amberlite XAD-7, and decylagarose . Antibodies prepared against macromomycin A showed antigenic identity by Ouchterlony double diffusion between the three purified proteins . This similarity was further demonstrated by their behavior on disc gel electrophoresis, the amino acid compositions, and comparative peptide mapping of the aminoethylated derivatives . They differed, however, in other chemical and biological properties . Auromomycin and macromomycin A, pI 5.4, have antibiotic activity, which is absent in macromomycin D, pI 5.2 . This antibiotic activity was associated with chromophore groups that were extractable by methanol . High-pressure liquid chromatography of the methanol extracts gave difference profiles for each of the purified proteins . The differences in the three proteins extended to their ultraviolet-visible spectra, fluorescence and circular dichroism, and the changes of these properties with heating . The heat denaturation, with auromomycin and macromomycin melting at 70.5 degrees C and macromomycin D at 57.0 degrees C, was reversible . Changes were noted in the spectra both during and following heating at 80 degrees C; the antibacterial activity was lost in auromomycin and only partially reduced in macromomycin A . The properties of the three proteins support the general similarities in their polypeptide structures, modifications in the properties of which are endowed by the differences in the associated nonprotein chromophores.

J Antibiot (Tokyo), 1982 Jul, 35(7), 843 - 9
Antibacterial effects of cefroxadine, cephalexin and cephradine in a new in vitro pharmacokinetic model; Schneider P et al.; A pharmacokinetic model has been developed, by means of which all possible time courses of the concentrations of antibiotics in the plasma of treated individuals can be exactly simulated in vitro without diluting the test organism and affecting the growth curves . Equieffective concentrations in the system corresponded to the plasma concentrations in man produced by cefroxadine in a single oral dose of 250 mg and cephalexin and cephradine in a single oral dose of 500 mg.

J Antibiot (Tokyo), 1982 Jul, 35(7), 806 - 13
Studies on the reconstitution of macromomycin a d auromomycin from the chromophore and protein moieties; Naoi N et al.; The chromophores extracted from macromomycin (MCR) and auromomycin (AUR) with methanol had identical ultraviolet absorption spectra, antibacterial spectra and analytical profiles in high pressure liquid chromatography . The chromophore content of AUR was about 8 times higher than that of MCR . MCR reconstituted from the chromophore and protein fraction was identical with native MCR by Sephadex G-50 chromatography, ultraviolet absorption spectrum and antibacterial spectrum . The antibacterial activity of MCR and AUR was due to the chromophore; the protein moiety had no activity . However, the protein moiety enhanced the activity of the chromophore against Gram-positive bacteria, while it suppressed the activity against Gram-negative organisms . It also protected the chromophore from heat-inactivation.

J Pharmacol Exp Ther, 1982 Jul, 222(1), 237 - 40
Vancomycin in rabbits: pharmacokinetics, extravascular diffusion, renal excretion and interactions with furosemide; Nivoche Y et al.; The pharmacokinetics, renal excretion, protein binding and extravascular diffusion of vancomycin in rabbits were studied . The effects of furosemide on these different parameters also were investigated . We observed a T 1/2 of 55 min and protein binding of 65% as determined in vitro by equilibrium dialysis . Vancomycin appeared to be secreted by renal tubules (fractional excretion: 177 +/- 44%) . In vitro, furosemide (5 micrograms/ml) slightly decreased the vancomycin protein binding (from 65 to 57%) . Furosemide significantly increased the renal excretion of vancomycin, through a tubular process without any effect on the filtered load . Vancomycin appeared slowly and at low concentrations in the extravascular fluid . The extravascular concentrations were higher when the antibiotic was administered by a 6-hr continuous infusion than when given by a 20-min infusion of the same dose . Our results suggested that the in vivo antibacterial effect to vancomycin could be enhanced by prolonged infusion . Also, it was demonstrated that furosemide has only a small effect on the kinetics of vancomycin.

Can J Comp Med, 1982 Jul, 46(3), 317 - 20
Coccidiosis in swine: dose and age response to Isospora suis; Stuart BP et al.; Coccidiosis is a disease of the young piglet due to infection with Isospora suis and is characterized by diarrhea which is nonresponsive to antibacterial therapy . There is variable morbidity and mortality . Piglets develop a more severe clinical illness and enteritis when infected with I . suis at one to three days of age than when infected at two weeks of age . Microscopic lesions range from villous atrophy and mild erosion to severe fibrinonecrotic enteritis.

J Rheumatol Suppl, 1982 Jul-Aug, 8, 10 - 7
The mechanisms of action of conventional chrysotherapy; Bluhm GB; The discovery of chrysotherapy occurred 90 years ago . Gold salts (GS) as an antibacterial agent were used initially for tuberculosis (TB), but an infectious etiology was also suspected for rheumatoid arthritis (RA) . Patients who received GS for TB and who also had RA noted improvement of their arthritis . The injectable GS regimen now commonly used evolved from the empirical use of GS for RA from 1920-1960 . Originally, clinical experience perpetuated the use of injectable GS to modify RA and its progression . However, scientific data obtained in the last 2 decades have supported the efficacy of chrysotherapy . Studies of protein binding, blood and serum concentrations, tissue distribution, and the toxicity of GS all provided suggestions for its mode of action . As chemical and cellular mediators of inflammation were uncovered, the possible actions of gold have been refined . Because the immune system seems to perpetuate rheumatoid inflammation, the interactions with GS continue to be studied . The in vitro and in vivo actions of GS with the immune system so far have provided conflicting data for its immunological effect . Studies by models of mucosal immunity may lead to new insights in the mode of action for gold.

Clin Pharmacokinet, 1982 Jul-Aug, 7(4), 312 - 35
Clinical pharmacokinetics of cerebrospinal fluid; Bonati M et al.; The distribution of drugs into the cerebrospinal fluid has long been considered a challenging field of investigation in 2 major respects: (a) understanding how the physicochemical properties (molecular weight, pKa, plasma protein binding) of various molecules influence their movements across such a specific structure as the blood-brain barrier; and (b) defining the relationship between cerebrospinal fluid concentrations of various drugs and their central (side) effects . An attempt has been made to review the very dispersed information presently available to offer a clinically orientated picture of this area of pharmacokinetics . Drugs acting on the central nervous system (benzodiazepines, tricyclic antidepressants, anticonvulsants, opioids), antibacterial agents, cardiovascular drugs (beta-adrenoceptor blockers and digoxin), antineoplastic drugs (mainly methotrexate), and other miscellaneous agents (corticosteroids, cimetidine, methylxanthines) are reviewed . The available evidence seems to support the conclusion that only for methotrexate and antibacterial agents does knowledge of cerebrospinal fluid pharmacokinetics have direct therapeutic implications, while the mosaic of information available for other drugs does little more than provide a partially satisfactory picture.

Clin Pharmacokinet, 1982 Jul-Aug, 7(4), 285 - 311
Rectal drug administration: clinical pharmacokinetic considerations; de Boer AG et al.; The human rectum represents a body cavity in which drugs can be easily introduced and retained and from which absorption is well possible . There are important therapeutic reasons why it is sometimes preferable to give a drug rectally rather than orally, e.g . in cases of nausea and vomiting . Drawbacks of rectal drug administration include the interruption of absorption by defaecation and lack of patient acceptability . The mechanism of drug absorption from the rectum is probably no different to that in the upper part of the gastrointestinal tract, despite the fact that the physiological circumstances (e.g . pH, fluid content) differ substantially, Absorption from aqueous and alcoholic solutions may occur very rapidly, which has proved to be of considerable therapeutic value in the rapid suppression of acute convulsive attacks by diazepam (e.g . in children), but absorption from suppositories is generally slower and very much dependent on the nature of the suppository base, the use of surfactants or other additives, particle size of the active ingredient, etc . There is some evidence that hepatic first-pass elimination of high clearance drugs is partially avoided after rectal administration, e.g . lignocaine . This can be explained by the rectal venous blood supply: the upper part is connected with the portal system, whereas the lower part is directly connected with the systemic circulation . Plasma concentration data following rectal administration of representatives of several classes of drugs are reviewed: anticonvulsants, non-narcotic analgesics and non-steroidal anti-inflammatory agents, hypnosedatives and anaesthetics, strong analgesics, theophylline and derivatives, corticosteroids, antibacterial agents, thiazinamium, promethazine, hyoscine-N-butyl-bromide, streptokinase, progesterone, ergotamine tartrate and levodopa . Only limited number of cases has it been adequately shown that the rectal route of administration gives plasma concentrations which are comparable to the oral route . Potentially the rectal route offers the same possibilities as the oral route, but the influence of the formulation seems to be very critical . It is also likely that the future novel drug delivery systems with zero order release characteristics will be applied rectally . Interesting preliminary results have already been obtained with theophylline administered by 2ml osmotic pumps.

Nouv Presse Med, 1982 Jun 19, 11(29), 2205 - 9
{Antibacterial therapy in surgery of the inner and middle ear . A study of co-trimoxazole penetration into the perilymph (author's transl)}; Jacob M et al.; Studies of the type presented here have rarely been undertaken and should be useful in surgery and pathology of the inner and middle ear . Samples of perilymph were collected during stapedectomy in patients with otosclerosis . In view of the very small volume of perilymph obtainable from each patient's vestibule (2 to 4 microliter), the only assay method that could be used to measure drug levels was thin layer chromatography on silica gel . Despite pooling of the perilymphs of 5 patients, trimethoprim (TMP) levels could not be measured but the authors were able to demonstrate that sulfamethoxazole (SMZ) does penetrate into the perilymph . Since the TMP-SMZ combination (co-trimoxazole) is active against the pathogens usually encountered in middle ear fluids, it is concluded that the drug could be of benefit in the treatment of middle and inner ear infections or after surgical operations on this area.

Pharmazie, 1982 Jun, 37(6), 410 - 2
Synthesis of some new heterocyclic 1,3,4-oxadiazoles with antibacterial activity; Ghattas AG et al.; 2-N-Aryl/heterocyclic carboxamidomethylthio-5-p-chlorophenyl-1,3,4-oxadiazoles have been synthesized by the reaction of 1 and N-aryl/heterocyclic-2-chloracetamides in presence of basic medium . 2 and 3 react with heterocyclic thiols in ethanolic potassium hydroxide to give 3-S-substituted-mercaptomethyl-5-substituted-phenyl-1,3,4-oxadiazol-2-thione 5 and 6 respectively . Tert . amines react with 2 to yield the corresponding amino chlorides in good yield . Some of the prepared compounds were tested as antibacterials against Gram-positive and Gram-negative organism.

J Antibiot (Tokyo), 1982 Jun, 35(6), 680 - 7
Hybrid biosynthesis of derivatives of protylonolide and M-4365 by macrolide-producing microorganisms; Sadakane N et al.; Biotransformation of a macrolide antibiotic and a related compound was studied using various macrolide-producing microorganisms grown in the presence of cerulenin, an inhibitor of de novo synthesis of the aglycone moiety . Protylonolide (1) was transformed into 5-O-(4'-O-propionylmycarosyl)protylonolide (2) by a leucomycin-producing strain, Streptoverticillium kitasatoensis KA-429 . M-4365 G2 (3) was bioconverted into M-4365 G3 (4), 9-dihydro M-4365 G3 (5), 3-O-acetyl M-4365 G3 (6) and 3-O-acetyl-9-dihydro M-4365 G3 (7) by a spiramycin-producing strain, Streptomyces ambofaciens KA-1028 . Forosaminylated derivatives of M-4365 G2 were not obtained using this microorganism . M-4365 G2 was converted into 3-O-acetyl M-4365 G2 (8) by Stv . kitasatoensis strain KA-429 and a carbomycin-producing strain, S . thermotolerans KA-442 . These results suggest that the substrate specificity of mycaminose- and forosamine-binding enzymes is high in Stv . kitasatoensis and S . ambofaciens, respectively, while that of the 3-hydroxyl acylating enzyme and mycarose-binding enzyme is low in these microorganisms . The bioconversion products showed lower antibacterial and antimycoplasmal activities than those of M-4365 G2.

Pathol Biol (Paris), 1982 Jun, 30(6), 389 - 93
{Antibacterian activity modifications of serum isoniazid when using it with rifampicin (author's transl)}; Nouhouayi A et al.; When dosing isoniazid in patients' serum after ingestion, the authors find a difference in the isoniazid levels when isoniazid is used alone, then, when isoniazid is used simultaneously with rifampicin . The level decreases or increases according to the inactivation index . They analyse the therapeutic consequences which can result from it . They infer, from the practical point of view, the necessity of : dosing isoniazid after having ingested it simultaneously with rifampicin and not alone when the efficient therapeutic dose is to be determined ; testing serum levels during antituberculous therapy for an eventual readjustment.

Pathol Biol (Paris), 1982 Jun, 30(6), 380 - 4
{Lung tissue diffusion of intravenous trimethoprim-sulfamethoxazole combination (author's transl)}; Morel C et al.; In 13 cases of pneumonectomy, we have studied the concentration of TMP-SMZ in tissue and serum, after three days of treatment . Four hours after TMP-SMZ injection, the tissue's samples obtained from crushed and mixed ; the dosages were performed by a microbiological assay . As we previously described in bronchial secretions : the lung penetration of TMP is important ; the tissue concentrations were higher than in serum ; the diffusion of SMZ is low . The ratio of TMP to SMZ were diffusion of SMZ is low . The ratio of TMP to SMZ were different in serum and tissue, but the antibacterial activity is not affected in vitro by the value's modification.

J S Afr Vet Assoc, 1982 Jun, 53(2), 87 - 90
The avermectins: A new family of antiparasitic agents; Hotson IK; The avermectins are macrocyclic lactones produced by fermentation of the soil micro-organism Streptomyces avermitilis . They show activity against a broad range of nematodes and arthropod parasites of domestic animals at dose rates of 300 microgram/kg or less . Unlike the macrolide or polyene antibiotics, they lack significant antibacterial or antifungal activity . By oral or parenteral administration, avermectins are active against gastrointestinal nematodes and lungworms, and important ectoparasites such as lice, mange mites, ticks and larval stages of flies . They show excellent activity against parasites resistant to existing anthelmintics or ectoparasiticides . The avermectins appear to cause paralysis of nematodes and arthropods by opening gamma-aminobutyric acid-mediated chloride channels at the neuromuscular junction.

Pediatr Med Chir, 1982 May-Jun, 4(3), 215 - 32
{Considerations about new cephalosporins}; Varese LA et al.; Spectrum of antibacterial activity, pharmacokinetics, adverse effects, dosage and therapeutic uses of newer cephalosporins are reviewed, following data of the most recent international works . AA . think that advantages of the new compounds in comparison with previous cephalosporins, are not so important that might modify their opinion on the role of cephalosporins in therapy: cephalosporins are useful, effective and safe chemotherapeutic agents, but all are overused and, only exceptionally, they could be claimed as a first choice antibiotics . Attempts should be made to define the precise indications for the use of the several members of the group before deciding which are really necessary, when it is really necessary . Newer cephalosporins should be reserved for situations in which they may be preferred to others chemo-antibiotics because of their relative safety or because of organism resistance to better established drugs . The present newer cephalosporins are generally effective when used wisely, in hospitalised patients, but therapy will often be significantly more expensive than a current chemo-antibiotic treatment.

Pharmazie, 1982 May, 37(5), 355 - 6
{Synthesis and antibacterial and antitumoral activity of some methylhydrazonium salts of pyrimidine bases and their analogues (author's transl)}; Golovinsky E et al.; On reacting pyrimidine metabolites containing a carboxyl or sulfhydryl group with methylhydrazine or N-benzyl-N'-methylhydrazine, various methylhydrazonium salts of these metabolites were synthetized, e.g., the salts of 5-fluororotic acid, 5-azaorotic acid, 2-thiouracil-5-carboxylic acid and 2-thio-6-azathymine . Some of these salts exhibited a more marked antibacterial activity against St . aureus and several of its mutants as well as a greater antitumoral activity against different transplantable tumours than their single components.

J Antibiot (Tokyo), 1982 May, 35(5), 602 - 8
Biosynthesis of vineomycins A1 and B2; Imamura N et al.; Biosynthetic studies of the antibacterial and antitumor antibiotics vineomycins A1 (1) and B2 (2), produced by Streptomyces matensis subsp . vineus, were carried out by labeling experiments with {1-13C}- and {1,2-18C2}sodium acetate followed by 18C NMR spectroscopy . The results show that the benz{a}anthraquinone chromophore of 1 is derived from a decacetate metabolite with decarboxylation at the carboxyl end and that 2 is formed via C-C bond cleavage of 1 . Isolation of rabelomycin from the fermentation broth of the same strain suggests a close biosynthetic relationship among the simple benz{a}anthraquinone antibiotics such as rabelomycin, tetrangomycin, aquayamycin, a C-glycosylated benz{a}anthraquinone, and vineomycins . These biosynthetic data prompted us to reconsider the previously published structure of the antibiotic SS-228Y, which has not been revised.

Br J Audiol, 1982 May, 16(2), 76 - 80
Some historical aspects of ototoxicity; Stephens SD; From a historical standpoint, the problems of ototoxicity came in two major stages . The first, in the nineteenth century, indirectly resulted from the chemical extraction, purification and, sometimes later, synthesis of the active components of traditional drugs, which led to their use in larger doses . The second stage, in the twentieth century, derived from the drive to find more and more effective antibacterial agents, which often had damaging side effects on the inner ear . These effects were highlighted by the development of more sophisticated techniques to detect and measure the ototoxic actions of drugs . The present brief account traces some early reports of ototoxicity from the time of Richard Morton (1692) onwards.

Antimicrob Agents Chemother, 1982 May, 21(5), 840 - 1
Antibacterial activity of matrix-bound ovotransferrin; Valenti P et al.; Ovotransferrin immobilized by covalent linkage to Sepharose 4B showed a bacteriostatic effect towards Escherichia coli similar to that of free ovotransferrin . The growth of the bacteria, after exposure to the gel-bound ovotransferrin and its removal, depended on the length of exposure . The results suggest that the antibacterial activity of transferrin is not due simply to the removal of iron from the medium.

Antibiotiki, 1982 May, 27(5), 378 - 82
{Effect of penicillin and erythromycin on immunity in angina}; Liashenko IuI; The number of T- and B-lymphocytes in the blood of patients with quinsy was practically the same with the use of either penicillin (101 persons) or erythromycin (115 persons) . The immunoglobulin concentration in the patients treated with penicillin at the beginning of the disease was normal, while during the period of reconvalescence the concentration of IgA and IgM increased . The concentration of IgA in the patients treated with erythromycin decreased at the beginning of the disease, especially when the disease was repeated . During the reconvalescence period it came to normal, while the level of IgM increased . When the patients were treated with penicillin, the increase in the titers of antistreptolysine-0- and antistreptokinase in the course of the disease was observed in 17.5 and 33.3 per cent of the patients, respectively . When the patients were treated with erythromycin the respective figures were 29.1 and 53.0 per cent . The shifts in the count of blood neutrophils including the functionally active ones in both groups of the patients were the same . It is concluded that penicillin prevented formation of humoral immunity in patients with quinsy because of its rapid antibacterial effect eliminating stimulation of the host immunocompetent cells . Erythromycin in addition inhibited production of IgA . The antibiotics had no effect on the number of T- and B-lymphocytes and neutrophils in the blood and function of T-lymphocytes and microphages.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1982 May, 252(1), 83 - 6
{Isolation of an antibacterial active tropolone from a Pseudomonas cepacia strain}; Korth H et al.; In the strain ATCC 17759 of Pseudomonas cepacia a highly antibacterial active substance was found, which could be identified as the tropolone bis-(3-hydroxy-2-oxocyclo-heptatrien-(3,5,7)-yl)-sulfide . This data confirm that tropolones are not only found in plants like western red cedars, but are also occurring as metabolites in bacteria . At least in Pseudomonas cepacia there seems to be an interesting reciprocal correlation between the production of tropolones and of phenacines . The purified tropolone showed a broad antibacterial activity spectrum against gram-positive and gram-negative microorganisms . The MIC-values were situated between 12.5 and greater than 100,0 microgram/ml.

Oral Surg Oral Med Oral Pathol, 1982 May, 53(5), 508 - 17
Antibacterial activity of gutta-percha cones attributed to the zinc oxide component; Moorer WR et al.; Growth of several species of bacteria was inhibited by the presence of endodontic gutta-percha cones . Microbiologic analysis, measurement of osmolarity, microscopy, x-ray diffraction analysis, and scanning electron micrography were used to identify the biologically active component that slowly leaches from gutta-percha cones . This component is zinc oxide in the form of small solid particles, from which active, soluble Zn2+ ion is mobilized by hydrolysis . A hypothesis on the "depot" effect of the ZnO particles is formulated, and is used to discuss some earlier reported literature on toxic and antibacterial activity of zinc oxide-containing materials . It is concluded that zinc oxide is not to be considered an inert compound . Its widespread uses in medicine and dentistry seem to reside in its "inert," biocompatible, and astringent properties mainly . The biologically active role of zinc oxide, however, merits further investigation.

Pharm Weekbl Sci, 1982 Apr 23, 4(2), 38 - 42
Microcomputer-controlled determination of dissociation constants of sulfanilamides and stability constants of the related silver complexes; Boelema GJ et al.; As a contribution to the structure-activity relationship of silver sulfanilamide complexes, the pKa-values of thirteen sulfanilamides and the log K-values of their related silver compounds were determined using a microcomputer-controlled titrator which determines the silver ion concentration and hydrogen ion concentration in a combined measurement . Predictions on antibacterial effectiveness and the risk of sensitization reactions of some of the investigated silver sulfanilamides are made on the basis of the conditional stability constants computed from the pKa- and log K-values at pH = 7.4.

Am J Obstet Gynecol, 1982 Apr 15, 142(8), 988 - 91
The relationship of amniotic fluid phosphate-to-zinc ratios to post-cesarean section infection; Minkoff HL et al.; Although many reports concerning risk factors for post-cesarean section febrile morbidity have been published, few have considered the antibacterial activity of amniotic fluid . This study, in which the amniotic fluid phosphate-to-zinc ratios were used as a reflection of antibacterial activity, demonstrates that, among 85 patients who underwent elective repeat cesarean sections, less febrile morbidity was present when the patient's amniotic fluid had greater antibacterial activity . There was less standard fever, use of antibiotics, and endometritis among patients whose amniotic fluid had lower phosphate-to-zinc ratios.

S Afr Med J, 1982 Apr 3, 61(14), 512 - 4
An evaluation of co-trimoxazole in the treatment of Plasmodium falciparum malaria; Hansford CF et al.; Two dosage schedules of co-trimoxazole, the standard antibacterial and a 2-day high-dose schedule, were compared with a standard course of chloroquine in the treatment of uncomplicated Plasmodium falciparum malaria . Parasites were cleared from the blood at similar rates, but pyrexia responded more slowly following the standard cotrimoxazole dose . No recrudescences were detected in those observed for up to 60 days after treatment.

Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol Bacteriol Virusol Parazitol Epidemiol, 1982 Apr-Jun, 27(2), 127 - 30
{Control of the effectiveness of antibiotic therapy by determining the antibacterial activity of the blood and cerebrospinal fluid}; Caruntu F; Determination of the antibacterial action of serum and the cerebrospinal fluid (CSF) is an excellent method for controlling the efficiency of antibioticotherapy in severe bacterial infections such as septicemia, endocarditis, meningitis . The author studied comparatively two methods for determining the antibacterial action of serum and CSF, namely dilution of the standard inoculum and diffusimetric methods . There was satisfactory agreement between the two methods . Hence, diffusimetry, a simple readily performed method, may be considered as an orientative test of the greatest utility, available for any of the lesser clinical laboratories.

J Antibiot (Tokyo), 1982 Apr, 35(4), 483 - 90
Cyclization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to penicillins by cell-free extracts of Streptomyces clavuligerus; Jensen SE et al.; Cell-free extracts prepared by sonication of Streptomyces clavuligerus cyclized delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) into a penicillin-type antibiotic . The antibacterial spectrum of this antibiotic suggested it was a mixture of isopenicillin N and penicillin N indicating that both cyclization and racemase activities were present . Cyclization activity was optimal in extracts prepared from 48 hours cultures . Extracts incubated at 20 degrees C produced antibiotic for 2 hours before activity ceased . Cyclization activity showed an absolute requirement for dithiothreitol (DTT) and O2 and was stimulated by ascorbic acid and FeSO4 . No requirement for ATP was observed.

J Antibiot (Tokyo), 1982 Apr, 35(4), 385 - 90
Production of antibiotic SU-2 complex by a 2-deoxystreptamine idiotroph of Micromonospora sagamiensis; Kase H et al.; A 2-deoxystreptamine idiotrophic mutant of Micromonospora sagamiensis, KY 11509, was found to produce unknown antibacterial substances, which were named SU-2 complex . Each component, SU-1, SU-2 and SU-3 were isolated from a culture broth of KY 11509 . Chromatographic data suggested that these components were new antibiotics . The antibiotics exhibited potent and broad spectrum of antibacterial activity . The amount of SU-1, SU-2 and SU-3 production reached their maximum level (197, 82 and 58 micrograms/liter, respectively) in 3 to 4 days . Addition of cobalt chloride markedly stimulated SU-1 production but suppressed SU-2 and SU-3 production . Isolation of a mutant possessing a higher productivity of SU-2 complex is also described.

Antibiotiki, 1982 Apr, 27(4), 243 - 7
{Antibiotic formation from a pyrimidine base group and an aminoglycoside group by a Streptomyces coeruleoaurantiacus sp . nov . culture}; Gauze GF et al.; An actinomycete strain 4009 was isolated from a soil sample collected in Volgograd . The strain showed a broad antibacterial spectrum . It produced antibiotics belonging to 2 different groups of chemical compounds, i.e . amycetin from the group of pyrimidine bases and nebramycin from the group of aminoglycosides . The antibiotic-producing organism is described as a type strain of Streptomyces coeruleoaurantiacus sp . nov . The new species is characterized by spiral spore chains, wart-like spore surface, blue aerial mycelium and dark yellow, orange-yellow or brown-orange-yellow substrate mycelium, the absence of soluble pigments on synthetic media and secretion of melanin pigments on the Tresner medium . Various conditions for submerged production of the antibiotic were studied.

Farmaco {Sci}, 1982 Apr, 37(4), 240 - 6
{Synthesis and tests of antibacterial activity of new analogs of d(+)-threo-1-(p-methylsulphonylphenyl)-2-dichloroacetamido-1,3-propanediol (thiamphenicol)}; Portelli M et al.; The synthesis of three new analogues of D(+)-threo-1-(p.methylsulphonylphenyl)-2-dichloroacetamido-1,3-propanediol (thiamphenicol) (I) which are D(--)-threo-2-(p.toluensulfophonamido)-1-(p.methylsulphonylphenyl)-1,3-propanediol (II), D(--)-threo-2-(p.aminobenzensulphonamido)-1-(p.methylsulphonylphenyl)-1,3-propanediol (III), D(--)-threo-2-(p.acetamidobenzensulphonamido)-1-(p.methylsulphonylphenyl)-1,3-propandiol (IV) is reported . The antibacterial activity of the compounds obtained was estimated in comparison with (I) in vitro and the therapeutic activity in vivo by experimental infection of the rat . The results showed the total absence of both types of activity.

Farmaco {Sci}, 1982 Apr, 37(4), 213 - 22
Bromination of 3-acyl-4-hydroxy-6 methyl-2H-thiopyran-2-ones . II; Caputo O et al.; The brominations of various 3-acyl-4-hydroxy-6-methyl-2H-thiopyran-2-ones as well as of 3-acyl-4-methoxy-6-methyl-2H-thiopyran-2-ones, bearing linear and branched acyl chains ranging from four to eight carbon atoms are described . The antibacterial and antimycotic activities of the new compounds are also reported.

Immunobiology, 1982 Apr, 161(3-4), 361 - 8
T lymphocyte-macrophage interactions in cellular antibacterial immunity; Hahn H et al.; Acquired resistance to facultative intracellular bacteria depends on a bicellular mechanism whereby specific T lymphocytes activate macrophages for enhanced bacteriocidal capacity . In vivo, protection is paralleled by delayed-type hypersensitivity . In vitro correlates are specific T lymphocyte proliferation and interleukin induction . Macrophage activation results from complex cell interactions involving both T lymphocytes and macrophages . Although such interactions are not yet fully understood, it appears likely that interleukin-facilitated collaboration between Lyt 1 and Lyt 123 T lymphocytes is required . Most probably, H2-restricted interactions between antigen-presenting mononuclear phagocytes and Lyt 1 T lymphocytes induce secretion of interleukins which further recruit additional Lyt 1 T lymphocytes from the Lyt 123 T lymphocyte set . In this way, the pool of Lyt 1 T lymphocytes capable of attracting and activating macrophages at the site of bacterial and implantation via lymphokines (macrophage activating factor, migration inhibition factor) could be markedly enhanced.

J Antibiot (Tokyo), 1982 Mar, 35(3), 266 - 71
A new antibiotic echinosporin (XK-213) - producing organism, isolation and characterization; Sato T et al.; Streptomyces echinosporus MK-213 produces a noval antibiotic echinosporin (XK-213) . Isolation of echinosporin was performed by absorption on activated carbon under acidic conditions and then eluted by aqueous acetone . The compound crystallized from methanol is a water soluble white solid composed of C10H9NO5 . Echinosporin exhibits weak antibacterial activities against Gram-positive and -negative microorganisms and its shows antitumor activity.

Am Rev Respir Dis, 1982 Mar, 125(3), 341 - 6
Endogenous peroxidase in the conducting airways of hamsters: morphologic evidence of synthesis and secretion; Christensen TG et al.; The lower respiratory tract of the hamster was examined for evidence of endogenous peroxidase activity . Using the standard diaminobenzidine cytochemical technique with controls to distinguish peroxidase from other hemoproteins, brown peroxidase reaction product was observed in the tracheal lumen and within epithelial secretory cells . The lumen and secretory cells of submucosal glands also contained peroxidase activity . Peroxidase-positive cells were most numerous in the upper trachea . Activity gradually decreased distally so that the least number of positive cells occurred in the extrapulmonary bronchus . Older animals contained many more positive cells than did younger animals . Within the lung, all epithelial cell types in both conducting and respiratory zones lacked activity . Peroxidase-positive cells in the tracheo-bronchial epithelium were identified as mucous cells by electron microscopy . Within these cells, peroxidase activity was found in the nuclear envelope, cisternae of rough endoplasmic reticulum, Golgi saccules, condensing vacuoles, and secretory granules . Discharge of the granules into the lumen appeared to result from a merocrine type of secretion . These ultrastructural findings are similar to those described for the secretory peroxidase in mammary and salivary glands . The peroxidase in these glands plays a key role in a nonspecific antibacterial system . Although the function of airway peroxidase is presently unknown, it is quite possible that it too possesses anti-infectious properties, thus forming an important adjunct to the well-known physical, cellular, and immunologic processes that protect the respiratory tract from microbial and toxic injury.

Rev Infect Dis, 1982 Mar-Apr, 4(2), 506 - 13
Antibacterial therapy for acute otitis media: a critical analysis; Marchant C et al.; Twenty-five published trials of antibacterial therapy for acute otitis media were reviewed according to 13 methodologic standards for the design of clinical trials . Randomized, controlled trials, often with the double-blind technique, have been widely applied to assess efficacy . Bias can be further avoided by prognostic stratification according to known risk factors and by the measurement and analysis of patient compliance with treatment . A less frequently recognized problem is the insensitive trial . Bacteriologic diagnosis of the middle ear exudate before therapy can improve the sensitivity of clinical trials . The eradication of pathogens from the middle ear may be a more sensitive measure of outcome than the reduction of ear effusion . The analysis of type II statistical error should be included in trials that reveal no difference between antibacterial agents . The evaluation of new antibacterial agents for this important health problem requires rigorous research design.

Rev Infect Dis, 1982 Mar-Apr, 4(2), 429 - 33
Adverse reactions to trimethoprim-sulfamethoxazole; Lawson DH et al.; A comprehensive review is presented of the world literature on adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) since its first use in 1968, when concern was expressed about possible hematologic toxicity . Serious toxicity is a rare event, but when it occurs severe skin lesions and thrombocytopenia/leukopenia are the most likely complications . Like other antibacterial agents, TMP-SMZ is associated with gastrointestinal upset, but adverse reactions affecting the kidney, liver, and fetus are rare . If the use of TMP-SMZ in pregnant women and in those known to be sensitive to the drug is avoided and if there is an awareness of possible drug interactions, therapy with the combination in the usual clinical setting is not associated with serious toxicity.

Rev Infect Dis, 1982 Mar-Apr, 4(2), 338 - 50
Trimethoprim-sulfamethoxazole in treatment of severe infections; Salter AJ; A retrospective comparison between clinical experience with trimethoprim-sulfamethoxazole (TMP-SMZ) and predictive laboratory investigations demonstrates that the most accurate predictions concern antibacterial activity of the drug against individual organisms . With regard to therapy for some relatively severe infections, clinical experience is limited and further research is needed . Some such studies that were not feasible in the past are now possible as a result of the availability of trimethoprim (TMP) as a single agent and of parenteral forms of both TMP and TMP-SMZ . The infections reviewed in this light herein include septicemia, endocarditis, meningitis, neonatal sepsis, anaerobic infections, ophthalmic infections, and infections due to "higher" bacteria and fungi . Based on current knowledge of in vitro drug activity, the clinical picture in such serious infections, and the experience with TMP-SMZ so far, it is predicted that TMP will be used either alone or in combination with other antibacterial agents (such as the polymyxins, metronidazole, and various sulfonamides in different ratios) for treatment of some of these infections.

Rev Can Biol Exp, 1982 Mar, 41(1), 47 - 63
{History and importance of electrically excitable artificial membranes}; Monnier AM; Solubility of narcotics in lipids has promoted the quest for non-aqueous and lipidic models of cell membranes . Artificial phosphatidic bilayers have been proposed . They display ionic conductance and excitability only if they are in contact with cyclic ion-carrier or specific substances, such as the protein fraction EIM . However many lipidic substances form non-bilayer membranes ion-conducting and excitable, without any specific additive . Only a small amount of free fatty acid is necessary . This is the condition for penetration through cation exchange . Coloured cations and cationic drugs undergo large exchange . Cu++, Hg++, emetine ++ cations have very high exchange coefficients which can be experimentally measured and which explain their respective antifungal, antibacterial and antiamoebian actions . The possible processes of membrane excitation are discussed . First the classical pores, specific of K+ and Na+ transfers and their "gating" mechanisms, because cell membranes are bi-ionic systems . Artificial membranes, are mono-ionic systems . But recent work shows that the axon membrane can be transformed into a monoionic system with Co++ as the only cations inside and outside the axon . Suggestions for the excitation processes are proposed . a) The assumption of a single energy barrier corresponding to minor conformational changes of structure . b) The membrane may be thixotropic . An outside cation penetrating the membrane would leave behind itself a wake of fluidity into which the next cations could penetrate if they follow each other closely . If they progress widely apart (under a small field), the ionic current would soon stop as the structure solidifies . c) The most promising suggestion is that anionic fixed charges in the membranes and cations form electrostatically bound ion-pairs . Dissociation of such pairs, that is conductance, augments markedly when dielectric constant increases . This process could be produced by water carried by incoming cations, that is by electro osmosis . This is exactly what occurs in Teorell's membrane oscillator in which a model membrane of fritted glass displays, under a weak current, oscillations of water flux and of potentials . The calculations pertaining to this model can be generalised if the electroosmotic water flux is assumed in increase the dielectric constant of the lipidic membrane . Thus the notion of an electroosmotic increase upon the dielectric constant of the membrane offers an alternative to the pore theory . Besides other phenomena show the role of low dielectric constants . The conductance of lipids containing coloured cations increase when subjected to illumination . The radiant energy absorbed then surpasses the association energy of ion pairs.

Jpn J Antibiot, 1982 Mar, 35(3), 724 - 30
{Studies on the combination action of ampicillin and dicloxacillin (author's transl}; Ohwaki H et al.; The combination action of ampicillin and dicloxacillin was studied in vitro . The following conclusions were obtained . 1) When both ampicillin and dicloxacillin were employed, an increase in antibacterial activity was observed against beta-lactamase producing E . coli No . 106 (clinical isolated strain) . 2) A synergistic action of ampicillin and dicloxacillin was proved by chequer board dilution method for E . coli No . 106 . 3) A same synergistic action of ampicillin and dicloxacillin was also proved by the growth curve for E . coli No . 106 . 4) Dicloxacillin showed an inhibition in degradation of ampicillin brought about by beta-lactamase extracted from E . coli No . 106 . 5) When the organisms of E . coli No . 106 were exposed to the combination of ampicillin and dicloxacillin, spheroplast-like structure and lysis were observed by scanning electron microscope.

Int Dent J, 1982 Mar, 32(1), 24 - 32
Oral effect of other carbohydrates; Krasse B; Historical data, epidemiological surveys, laboratory and animal experiments, clinical studies and observations in ordinary dental practice all illustrate that starchy fibrous foods have a low cariogenic potential . The recommended substitution of sucrose in Western diets by starchy foods would lead to a reduction of caries provided that these other carbohydrates replace the between meal consumption of sugar-rich products . The low cariogenic potential of a diet containing carbohydrates with a fibrous character is probably not solely due to its low sucrose content . Such a diet promotes mastication and saliva secretion which tend to reduce the caries risk . Furthermore, unrefined foods may contain caries-protective substances like phytates, trace elements and antibacterial factors . Lectins, which are found in many plants could be of importance by influencing the attachment of micro-organisms to the teeth in a favourable manner . The tradition to end a meal with fruit may thus have other oral effects than hitherto considered . In addition, a diet containing carbohydrates with a fibrous character and a low amount of sucrose probably has a low pathogenic potential for the periodontal tissues . However, no epidemiological data are available to support this assumption.

J Med Chem, 1982 Mar, 25(3), 271 - 5
Novel dimeric derivatives of leucomycins and tylosin, sixteen-membered macrolides; Omura S et al.; The reductive amination of an aldehyde group on the aglycon moiety of leucomycins A3 and A5 and tylosin with sodium cyanoborohydride in the presence of NH(CH3)2 or NH2CH3 afforded the corresponding amine derivative . The use of NH3 as an amine source in the reduction of leucomycin A3 and tylosin afforded a novel dimeric derivative, 18,18'-dideoxo-18,18'-iminodileucomycin A3 and 20,20'-dideoxo-20,20'-iminoditylosin, respectively . The structures of the dimers were elucidated by field desorption mass spectral analysis . The dimeric derivative of tylosin possesses considerable antibacterial activity . The binding activity of the dimer of Escherichia coli ribosome was approximately the same as for tylosin.

Medicine (Baltimore), 1982 Mar, 61(2), 109 - 24
Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity; Binder RE et al.; We conclude that chronic necrotizing pulmonary aspergillosis is a clinical entity which has not usually been recognized as one of the forms of pulmonary disease due to Aspergillus species . Patients are middle-aged, and often have some evidence of impairment of host defenses such as diabetes mellitus, a connective tissue disorder, poor nutrition, chronic obstructive lung disease or low dose corticosteroid therapy . They are almost always symptomatic with fever and a productive cough, and their chest roentgenogram shows infiltrative and cavitary disease, typical of a chronic destructive lung process such as tuberculosis or anaerobic infection . Cavity formation is often accompanied by the development of a mycetoma . The disease is usually of 1 to 6 months duration but can be present for years prior to diagnosis . The diagnosis is suggested by the clinical course and the isolation of the fungus from pulmonary secretions; negative cultures for other pathogens and failure to respond to antibacterial or antimycobacterial therapy are characteristic . The diagnosis is confirmed by pathologic evidence of tissue invasion by the fungus or a response to specific antimycotic therapy . The symptomatic response to antifungal chemotherapy, at times combined with surgical drainage or resection, is favorable . However, roentgenographic resolution is not uniform, and many patients have residual cavitary disease . The long-term prognosis is uncertain.

Clin Pharm, 1982 Mar-Apr, 1(2), 169 - 76
Zinc deficiency dermatitis accompanying parenteral nutrition supplemented with trace elements; Moran DM et al.; Zinc deficiency dermatitis in a patient on long-term total parenteral nutrition (TPN) with trace-element supplementation is reported, and the therapeutic aspects of zinc deficiency are reviewed . A 36-year-old white man was hospitalized and found to have a small-bowel perforation secondary to internal herniation . Small-bowel resection with end-to-end anastomosis was performed, and TPN supplemented with folic acid, multivitamins, trace elements (including elemental zinc 2 mg/day), and fat was begun . Four months later, the patient developed a moist, erythematous, painful groin rash that did not respond to one month of topical antifungal and topical and intravenous antibacterial treatment . At five months after admission, zinc deficiency was suspected; serum zinc concentration was 85 micrograms/dl (normal = 55-150 micrograms/dl) . The total daily zinc dose was increased to 60 mg, and within two days the patient's lesions began to improve . The rash healed within two weeks . Six days after increased zinc therapy was begun, lab tests showed: hair zinc content, 185 micrograms/g (normal = 163 micrograms/g); serum zinc content, 90 micrograms/dl; and erythrocyte zinc content, 1058 micrograms/dl (normal = 1100-1400 micrograms/dl) . Signs and symptoms of zinc deficiency, zinc disposition in man, predisposing factors to zinc deficiency, laboratory analysis of zinc nutriture, zinc therapy, and zinc toxicity are discussed . Knowledge of drug use, diet, geographic location, underlying disease, and other patient-specific factors is important in recognizing the patient at risk of developing zinc deficiency . Several tests should be performed to document zinc deficiency . Zinc replacement guidelines are outlined.

Eur J Cancer Clin Oncol, 1982 Mar, 18(3), 271 - 9
A comparison of the requirements for antitumour activity and antibacteriophage lambda activity for a series of non-intercalative DNA-binding agents; Robertson IG et al.; A series of non-intercalative DNA-binding agents, comprising mainly bisquaternary ammonium heterocyclic compounds, has been found to inhibit strongly the production of bacteriophage lambda following its induction in Escherichia coli . The inhibition is much greater than that found with a number of DNA intercalating agents, including 9-aminoacridine, ethidium and Daunorubicin . The inhibition correlated significantly with antitumour effect, as measured in a life extension assay with L1210 leukaemia . Activity in both biological systems demanded the presence of strongly charged groups and a rigid co-planar aromatic skeleton, these requirements being almost identical to those needed to displace ethidium efficiently from DNA in a simple assay system . It is suggested that biological activity is associated with the ability of these agents to bind in the minor groove of the DNA double helix . Data on the antibacteriophage action of one of these agents suggests possible models for antitumour activity.

Jpn J Antibiot, 1982 Feb, 35(2), 369 - 74
{The combination therapy of amikacin and beta-lactam antibiotic in the severe bacterial infections (author's transl)}; Takigami T; The combination therapy of beta-lactam and aminoglycoside antibiotics is now evaluated to be very effective in severe infections . Amikacin, one of aminoglycoside antibiotics, has antibacterial activity to gentamicin resistant bacteria . Then we tried to use the combination therapy of amikacin and beta-lactams in 20 cases with severe bacterial infections, including 2 cases of bacteremia etc . Fifteen cases out of them failed to cure by previous antibiotics treatment . With a few exception, amikacin was administered daily 200 mg in 2 divided intramuscular injections . beta-Lactams were administered twice a day by intravenous drip infusion, but dose and kind of beta-lactams were decided by attending doctors . Clinical efficacy of this combination therapy was classified in 4 degrees: excellent, good, fair and poor . Clinical efficacy rate (excellent and good results) in all cases was 75% . This is equally effective, compared with the newly sold antibiotics . Elevation of serum GOT and GPT levels was seen in 2 cases in whom large amount of PCs was given . As a conclusion, it was indicated that the combination therapy of amikacin and beta-lactam in the regular dose was sufficiently effective and useful for the therapy of severe bacterial infections.

J Pharm Sci, 1982 Feb, 71(2), 178 - 82
Synthesis and biological investigations of some 5H-1,3,4-oxadiazolo{3,2-a}pyrimidin-5-ones; Soliman FS et al.; The synthesis of some substituted 7-hydroxy-5H-1,3,4-oxadiazolo {3,2-a}pyrimidin-5-ones, a class of bicyclics with unexplored pharmacotoxicological properties, is described . Reacting the 2-phenyl derivative with bis(2,4,5-trichlorophenyl)benzylmalonate afforded a linear pyrano-oxadiazolopyrimidinedione . The assigned structures were verified by IR, 1H-NMR, and mass spectral studies . Six compounds of the series were screened for in vitro antibacterial and antifungal activities . The effect of four compounds on alkaline phosphatase enzyme was also examined.

Tijdschr Diergeneeskd, 1982 Feb 1, 107(3), 85 - 92
{Residues in products of animal origin (author's transl)}; Ruiter A; Products of animal origin may contain a variety of substances regarded as 'residues': traces of veterinary drugs and their metabolites, environmental contaminants, traces of compounds having injurious effects, which have their origin in the manufacturing process, and mycotoxins . Some of these substances are carcinogenic, others may impair the functions of organs or cause disturbances of hormonal balance . Antibacterial substances may induce resistance of pathogenic agents and, finally, a number of substances give rise to sensitivity reactions . Standards for permissible amounts are required in several cases; a number of substances should be completely omitted so that their use should be prohibited; adopting the concept of 'zero tolerance', however, may present problems . Extensive analysis is only practicable so far in a few cases . Rapid screening procedures will have to be developed in the future, in which immunochemical methods may play a particularly important role.

Acta Pathol Microbiol Immunol Scand {C}, 1982 Feb, 90(1), 1 - 6
Immune protection against enterotoxinogenic E . coli: search for synergy between antibodies to enterotoxin and somatic antigens; Svennerholm AM et al.; The protective effect against intestinal challenge with enterotoxinogenic (ent+) E . coli of enterotoxin antibodies alone and in combination with various antibacterial antibodies has been studied in rabbits . Both antibodies against E . coli heat-labile enterotoxin (LT) and cholera toxin were equally effective against different serotypes of ent+ E . coli . Antiserum to purified homologous E . coli lipopolysaccharide (LPS) as well as to cross-reactive LPS structures (Re LPS and Common antigen) contained protective antibodies which increased the protection obtained with anti-enterotoxin . Antiserum to whole bacteria acted synergistically with anti-LT against homologous and sometimes also against heterologous E . coli . This synergy remained after complete absorption of the LPS antibodies from the antibacterial serum.

Infect Immun, 1982 Feb, 35(2), 396 - 401
Escherichia coli-associated porcine neonatal diarrhea: antibacterial activities of colostrum from genetically susceptible and resistant sows; Sellwood R; Antibacterial properties of colostrum from genetically resistant and susceptible sows in a herd in which only the susceptible sows had acquired natural immunity to K88-positive Escherichia coli have been investigated . Significant differences in antiadhesive and opsonic activities occurred . Colostrum from susceptible sows inhibited the binding of 125I-labeled K88 antigen to brush borders significantly better than did the colostrum from resistant dams . Colostrum from susceptible dams effected more efficient in vitro opsonic phagocytosis and killing of K88 E . coli than did colostrum from resistant dams . Differences in bactericidal properties of colostrum between the two groups of pigs were not significant . Fractionation of colostrum from susceptible dams by gel filtration and ion-exchange chromatography revealed that the fractions rich in immunoglobulin M had the highest opsonic activity, whereas those containing predominantly immunoglobulins G and A were of lower activity.

Vox Sang, 1982 Feb, 42(2), 62 - 73
Characterization of various immunoglobulin preparations for intravenous application . I . Protein composition and antibody content; Romer J et al.; In this comparative study we investigated 14 immunoglobulin (Ig) preparations for intravenous application; they were prepared by various manufacturers who used either placental or venous blood as the starting material . The pepsin- and plasmin-treated products and a preparation which, according to the manufacturer, was not degraded enzymatically, contained 17-86% of IgG split products . On the other hand, three chemically modified preparations, one preparation treated at pH 4, for products treated with poly(ethylene glycol) (PEG) and one preparation protected by albumin contained 90% or more of non-fragmented IgG . The IgG subclass distribution corresponded to the distribution of subclasses in normal serum only in the nonmodified and not enzymatically degraded preparations . All samples except one contained 0.1 mg/ml IgA or more, all contained only traces of IgM . No product had clinically relevant titers of irregular antibodies against erythrocyte antigens . The content of those antiviral and antibacterial antibodies that were tested for was similar in all preparations . Only the anti-HBs activity exhibited large variations . Some PEG-treated preparations showed an elevated prekallikrein activator (PKA) level, whereas all other preparations contained, if any, only traces of PKA.

J Antibiot (Tokyo), 1982 Feb, 35(2), 176 - 83
New anthracycline glycosides: 4-O-demethyl-11-deoxydoxorubicin and analogues from Streptomyces peucetius var . aureus; Cassinelli G et al.; The new anthracyclines 4-O-demethyl-11-deoxydoxorubicin, 4-O-demethyl-11-deoxydaunorubicin along with its 13-dihydro and 13-deoxo analogues are the main components of the anthracycline complex produced by cultures of Streptomyces peucetius var . aureus . They were isolated by solvent partition, separated by column chromatography and characterized by chemical and physical methods . Among these new anthracyclines, displaying antibacterial and cytotoxic activity "in vitro", 4-O-demethyl-11-deoxydoxorubicin and the corresponding daunorubicin analogue were also active against experimental tumors.

Antimicrob Agents Chemother, 1982 Feb, 21(2), 254 - 8
Penetration of cephalosporins and corresponding 1-oxacephalosporins through the outer layer of Gram-negative bacteria and its contribution to antibacterial activity; Murakami K et al.; 1-Oxacephalosporins had a higher ability to penetrate through the outer layer of the envelope of gram-negative bacteria than the corresponding cephalosporins . In spite of the liability of 1-oxa congeners to beta-lactamases, they attained higher periplasm concentrations at a given concentration outside the cells . The replacement of sulfur in the cephem nucleus by oxygen was accompanied by an increment of the hydrophilic character of the molecule, which suggests that this character was favorable for outer layer penetration . 1-Oxacephalosporins showed enhanced antibacterial activity in short-term measurement and exerted their antibacterial action at lower periplasm concentrations . Thus, the enhanced antibacterial activity of 1-oxacephalosporins seems to be due to their higher penetrability and their intrinsic inhibitory activity against the peptidoglycan biosynthesis system.

J Toxicol Environ Health, 1982 Feb, 9(2), 317 - 25
Volcanic ash: toxicity to isolated lung cells; Castranova V et al.; Samples of volcanic ash from Mount St . Helens were collected from Spokane, Washington, after the major eruption of May 18, 1980 . The toxicity of ash to the lung was estimated by monitoring the effects of in vitro and in vivo exposure on various physiological parameters of isolated lung cells . Volcanic ash had little effect on O2 consumption of rabbit type II pneumocytes, O2 consumption or superoxide release of resting rat alveolar macrophages, or membrane integrity of rat alveolar macrophages . Ash also caused no significant lipid peroxidation in rat lung microsomes . However, volcanic ash did inhibit superoxide anion release from zymosan-stimulated rat alveolar macrophages . Since superoxide is an antibacterial substance, this result suggests that exposure to volcanic ash may adversely affect the ability of alveolar macrophages to protect the lung from infection.

Lancet, 1982 Jan 2, 1(8262), 5 - 6
Co-trimoxazole alone for prevention of bacterial infection in patients with acute leukaemia; Starke ID et al.; 43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia . There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired . Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Mikrobiyol Bul, 1982, 16(4), 259 - 67
{The in vitro antibacterial values of oxpara liquid, N2 medical liquid and merfen}; Duruk H et al.; The disinfectants called Oxpara liquid, N2 medical liquid and merfen are being used in the treatment of pulp and periapical tissue infections in medical dentistry . In the clinics of H . U . Medical Dentistry Faculty these disinfectants are used in their undiluted, concentrated forms . As it was thought they might be harmful to the tissues in their concentrated forms, it was attempted to find out their least toxic but sufficiently effective dilutions on different bacteria, compared with pheunol . In the light of findings the in vivo values were investigated in another work . The Inhibition Coefficients (IC) for S . aureus were found to be 1/100 in phenol and Oxpara liquid, 1/1000 in Merfen, for S . typhi 1/200 in phenol and N2 medical liquid, 1/2000 in Oxpara liquid and Merfen . The Inferior Lethal Coefficients (ILC) for S . aureus were found to be 1/90 in phenol, 1/80 in phenbol, 1/80 in Oxpara liquid, 1/100 in N2 medical liquid, 1/1400 in Merfen, and for S.typhi 1/100 in phenol and N2 medical liquid and 1/700 in Merfen . The Superior Lethal Coefficients (SLC) for B.subtilis were found to be 1/80 in phenol, in Oxpara and N2 medical liquids, and 1/500 in merfen . When Phenol Coefficients were considered, Oxpara and N2 medical liquids were found to be in equal strength with phenol as antibacterial agents, however Merfen was approximately 15 times stronger than phenol.

Biomed Pharmacother, 1982, 36(8-9), 375 - 7
Antibacterial activity of liposome-entrapped streptomycin in mice infected with mycobacterium tuberculosis; Vladimirsky MA et al.; Streptomycin sulfate was entrapped in liposomes obtained from lecithin by a detergent method at the ratio of 250-300 mcg streptomycin-base per 1 mg of lecithin . Intravenous injection of liposome-entrapped streptomycin (LES) to the mice infected with Mycobacteria tuberculosis H37 Rv led to a statistically significant decrease in the spleen mycobacterium number, but not in the lungs, as compared to the buffered solution of streptomycin (SS) . Intravenous treatment of the mice with LES resulted in prolonged mouse survival, as compared to that with SS . Acute streptomycin toxicity was also reduced by its intravenous administration in the form of LES.

Mikrobiologiia, 1982, 51(5), 823 - 31
{Taxonomy of fluorescent streptomyces based on a comparative population analysis}; Kuznetsov VD et al.; A revision of the taxonomy for the fluorescent subgroup of streptomycetes has confirmed experimentally that it is expedient to use the comparative population-taxonomic analysis as a new approach to the taxonomy of actinomycetes, which makes it possible to establish relationships between cultures being compared . It has been shown that the species Streptomyces galbofluorescens and S . fluorescens are merely spontaneous variants in the composition of the parent population of S . chrysomallus and therefore bear no taxonomic and nomenclature status . Consequently, the fluorescent subgroup consists of two (rather than the earlier described four) species: S . chrysomallus and S . citreofluorescens . The names S . galbofluorescens and S . fluorescens should be regarded as synonyms of the name S . chrysomallus . The culture of S . chrysomallus was found to contain a water-soluble antibacterial antibiotic . Three monosynthetic variants were isolated from the population of S . chrysomallus.

Eur J Drug Metab Pharmacokinet, 1982, 7(3), 197 - 202
The pharmacokinetics of tetroxoprim in the dog; Vergin H et al.; The pharmacokinetics and metabolism of the newly developed antibacterial tetroxoprim (TXP) were investigated in four male beagle dogs using a 2-(14C)-labelled drug . TXP was administered intravenously and orally at doses of 5 mg/kg bodyweight . Counting of the total 14C-radioactivity shows that the drug was absorbed completely and eliminated almost exclusively by the kidneys . The quantitative absorption of TXP from the canine gastro-intestinal tract was ascertained by comparison of the AUC-values and the renal recoveries of unchanged drug following i.v . and oral dosage . The terminal half-lives of non-metabolized compound in plasma were 4.64 and 4.83 for i.v . and oral dosing respectively . Following either i.v . or oral TXP administration, the major route of excretion was renal elimination of the compound as its major metabolite U-1 (81-82.2% of dose) and as unchanged mother substance (11.4-12.3% of dose).

Chemotherapy, 1982, 28 Suppl 1, 32 - 6
In vitro antibacterial activity of different clotrimazole formulations; Schaller K; The antibacterial activity of two different clotrimazole formulations was tested in vitro . A neutral vaginal tablet with 100 mg active ingredient has a partial bactericidal effect on gram-positive bacteria . A new formula containing 500 mg clotrimazole and lactic acid, designed for a one-dose therapy of vulvovaginal mycoses, shows an improved bactericidal activity against gram-positive bacteria and, owing to the lactic acid content, a broad bactericidal effect on gram-negative species.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1982, 176(5-6), 485 - 91
Complex studies of the influence of the working conditions in the Plock Petrochemical Plant on the behaviour of some parameters of cell immunity; Denys A et al.; Complex evaluations of the function of peripheral blood granulocytes in the Phenol Plant workers were made . Only precise examinations of the bactericidal and ingestive functions as well as the metabolism of those cells may lead to the discovery of a clinically unnoticeable insufficiency of the system as has been confirmed by other authors and by our own previous studies . Routine methods of separating granulocytes of heparinized peripheral blood were used . Phagocytic activity of cells after contact with three antigens was studied . Bactericidal activity of granulocytes in the presence of Staph . aureus and antibactericidal activity of lysosomal proteins of granulocytes were evaluated . According to the general assessment, no permanent disturbances of the granulocyte function were observed in the phenol plant workers . However, disturbances of the phagocytic and bactericidal abilities were detected in some individual cases . In general evaluation no disturbances of function of granulocytes concerning all some cases phagocytary and bactericidal abilities did not occur simultaneously.

Antibiotiki, 1982, 27(9), 701 - 4
{Pharmacokinetic interaction of antibiotics and pathogenetic agents in suppurative meningitis}; Klimova EA et al.; The effect of the widely used pathogenetic agents, such as detoxicating fluids and diuretics on the pharmacokinetics of antibiotics, i.e . benzylpenicillin, ampicillin and levomycetin was studied . It was shown that infusion of the detoxicating fluids had an effect on the antibiotic blood levels which depended on the volume of the fluid used . The pharmacokinetics of the antibiotics was found to be changed when the antibiotics were used simultaneously with the diuretics . This is of a special importance for documenting the tactics of antibacterial therapy in patients with meningitis complicated by the brain edema, since intensive dehydration therapy is required in such cases . Significant changes in the pharmacokinetic interaction of the antibiotics with different diuretics, i.e . mannitol, lasix and furosemide were demonstrated . Respective recommendations for the medical practice were developed on the basis of this study.

J Chronic Dis, 1982, 35(10), 803 - 16
A methodologic study of post-marketing drug evaluation using a pharmacy-based approach; Borden EK et al.; There has been an increasing interest in monitoring medications in their customary use after they are marketed . A variety of approaches have been discussed . This study was undertaken to test the feasibility of assembling a cohort of patients receiving target medications through the pharmacist and following the patients for their health course over a period of one month . The class of drugs chosen with oral antibacterials . The logic and strategy of this approach as a model is presented along with the methods and the results.

Infection, 1982, 10 Suppl 2, S92 - 8
{Binding, distribution and efficacy of erythromycin (author's transl)}; Dette GA; The significance of the binding of antibiotics in humans in still a controversial question . In principle, only free, unbound antibiotic is considered to be diffusible and biologically active . With unimpaired measurements and a binding balance within the normal therapeutic concentration range, the free portion of erythromycin in the human serum is found to depend significantly on the total concentration of erythromycin . For example, for concentrations of 1, 16 and 24 mg/l, approx . 74%, 54% and 46% are bound (+38 degrees C) . binding is temperature-dependent and decreases with decreasing temperature . At +4 degrees C, 44% of 1 mg/l and 30% of 16 mg/l are bound . These binding characteristics are based in part on the properties of erythromycin's major binding partner in the serum - acidic alpha1-glycoprotein . Albumin only contributes slightly to the overall binding and is not concentration-dependent in the therapeutic range, i.e . it cannot be saturated . Binding phenomena have a decisive influence on the distribution of an antibiotic within an organism . In the case of erythromycin, the tissue levels in nearly every organ are higher, sometimes considerably higher, than the corresponding serum levels . We have shown the binding of erythromycin to cytosol and particle fractions in certain organs and compared this to the binding in the serum.The antibacterial principle regarding the efficacy of erythromycin is also based primarily on a binding reaction which maintains the concentration gradient for the intake of erythromycin in microorganisms . The kinetics ofintake (microorganism) are compared to those of binding (macroorganism) and referred to the minimum inhibitory concentration.

Curr Med Res Opin, 1982, 8(1), 5 - 8
Peroperative cephradine concentrations in the gall bladder wall and bile; Bullen BR et al.; Cephradine levels were assayed in serum, gall bladder wall and bile sampled from the gall bladder and common bile duct in 24 patients undergoing elective cholecystectomy . Cephradine was administered either as 1 g given intravenously at the time of anaesthetic induction, or as three 6-hourly doses of 0.5 g taken orally during the pre-operation day followed by 1 g intramuscularly with the premedication . Adequate antibacterial levels of cephradine were achieved in all serum samples, 8 of 9 samples of choledochal bile, 6 of 12 samples of cholecystic bile and all 12 samples of gall bladder wall in the group receiving a single intravenous dose, compared to only 4 of 12 serum samples, 6 of 11 choledochal bile samples, 6 of 10 cholecystic bile samples, and only 3 of 12 samples of gall bladder wall in the group receiving oral cephradine . Therefore, cephradine given as a 1 g bolus intravenously with anaesthetic induction provides satisfactory concentrations for antibacterial prophylaxis during gall bladder surgery but a regimen of oral and intramuscular dosage was found to be unsatisfactory.

Infection, 1982, 10(2), 85 - 9
{Clinical experience with non-specific broad-spectrum antibacterial chemotherapy (author's transl)}; Shah PM et al.; 49 patients were given cefoxitin in combination with azlocillin, and 15 were given an aminoglycoside as well when severe bacterial infection was suspected . In 39 cases a prompt amelioration of the clinical signs of infection was observed . Of the 17 patients who died, a post-mortem was performed in seven; only in four were signs of bacterial infection present; one had tuberculosis and one had a cytomegalovirus infection . The combination therapy was well tolerated and side-effects were rare; no bleeding complications were seen . Clinical signs of possible antagonism between the two beta-lactam antibiotics were not observed.

Arkh Patol, 1982, 44(3), 13 - 8
{Clinico-anatomic characteristics of sepsis caused by polymicrobial flora}; Ageev AK et al.; Pathological examinations of 23 fatalities due to sepsis caused by polymicrobial flora revealed in 7 cases polymicrobial flora in metastatic foci of dissimilar composition in different foci, in 4 cases monomicrobial flora but varying in different foci, in 12 cases monomicrobial flora similar in all examined septic foci despite the presence in the blood of two or more agents . Localization of metastatic septic foci to a certain extent dependent on the nature of the sepsis causative agents comprising the association . Polymicrobial forms of sepsis were found in fatal cases due to leukemia in 50.0%, to burn sepsis in 10.8%, and to other diseases in 2.8% of the cases, indicating the dependence of their development on the degree of reduction of immunological responsiveness of the patients . The effect of antibacterial therapy given to the patients on the etiology of sepsis is discussed.

J Antibiot (Tokyo), 1982 Jan, 35(1), 46 - 57
Diastereomeric fortimicin 1,2-epoxides . The preparation of the 1-deamino-2-deoxyfortimicins A and B and the 1,2-di-epi-fortimicins A and B; Martin JR et al.; The preparation of 1,2-anhydro-2',6'-di-N-benzyloxycarbonyl-1-deaminofortimicin B-4,5-carbamate (4) and its conversion to the two diastereomeric 2',6'-di-N-benzyloxycarbonyl-1-deamino-2-deoxy-1,2-epoxyfortimicin B-4,5-carbamates 7 and 13 are described . The olefin 4 was used for preparation of 1-deamino-2-deoxyfortimicin A (6d) while the beta-epoxide 13 was used for the preparation of 1,2-di-epi-fortimicin A (17b) and 2-amino-1-deamino-2-deoxy-1-hydroxyfortimicin A (19c) . The in vitro antibacterial activities of 6d, 17b and 19c are reported.

Acta Otolaryngol, 1982 Jan-Feb, 93(1-2), 69 - 72
Prescription of antibacterial drugs for treatment of otitis media and upper respiratory tract infections in general practice in Denmark; Mabeck CE; In a multipractice study 577 general practitioners registered all patients to whom they prescribed antibacterial drugs . In all, 7849 patients were registered . Of these, 40% were treated for upper respiratory tract infection or otitis media . Seventy-seven per cent of all patients treated for otitis media were less than 15 years of age . Sixty-seven per cent treated for sinusitis, and 55% of all patients treated for tonsillitis acuta were between 15 and 45 years . Significantly more women than men were treated for sinusitis, while the same number of men and women were treated for otitis media and tonsillitis acuta . Of all acid-stable and broad-spectrum penicillins prescribed in general practice, 63% and 47% respectively were used in the treatment of upper respiratory tract infection or otitis media . Acid-stable penicillins were prescribed for the majority of patients with otitis media and acute tonsillitis treated with antibacterial agents . By contrast, only 22% of patients with sinusitis were treated with phenoxymethyl-penicillin, while 36% of these patients were treated with azidocillin . Seventy-three per cent of all azidocillin prescribed in general practice was used in the treatment of patients with sinusitis.

Infection, 1982 Jan, 10(1), 31 - 4
Antibacterial kinetics of ampicillin against Escherichia coli under simulated in vivo conditions; Fuglesang JE et al.; We studied the response of Escherichia coli to ampicillin concentrations which decreased logarithmically at elimination half-life values (t1/2a) ranging from one to four hours . The rate of bacterial killing depended on the initial antibiotic concentration (co), but was not significantly affected by t1/2a . Irrespective of co and t1/2a, the bactericidal effect terminated after about three hours of exposure to the drug.

Infect Immun, 1982 Jan, 35(1), 143 - 50
Generation of enhanced macrophage-mediated antibacterial resistance in animals responding to tumor allografts; Newborg MF et al.; Enhanced systemic antibacterial resistance was acquired by ACF1 (H-2ad) and B6D2F1 (H-2bd) mice bearing allogenetic BP-3 (H-2b) and SA-1 (H-2a) footpad tumors, respectively . This effect was dose dependent, in that the implantation of greater numbers of tumor cells produced larger tumors and higher levels of nonspecific resistance . Although the rejection of the tumor was T-cell dependent, the generation of nonspecific resistance was not . Thus, T-cell-deficient mice bearing progressively growing tumor allografts generated significant levels of antibacterial resistance . Two mechanisms were found to be involved in the generation of nonspecific resistance: (i) an acquired radioresistant mechanism responsible for initially destroying a large proportion of injected bacteria and (ii) an acquired radiosensitive mechanism responsible for destroying a significant number of bacteria after 24 h.

Scand J Infect Dis Suppl, 1982, 33, 115 - 20
The effect of antibacterial agents on the association between bacteria and leukocytes; Forsgren A et al.; The effect of antibacterial agents on human lymphocyte chemotaxis, phagocytic capacity, protein synthesis and the relation between morphologic and functional changes induced by antibacterial agents was studied . A significant depression of chemotaxis measured with an agarose gel technique was detected when human leukocytes were incubated with fusidic acid and rifampicin in clinically obtainable concentrations . The newer, well absorbed tetracyclines depressed chemotaxis at high concentrations, but a less pronounced inhibition was detected with classical tetracycline . The incorporation by human neutrophils of 14C-leucine into a trichloroacid insoluble fraction was markedly depressed by the same antibiotics, and it is suggested that some antibiotics acting by inhibition of protein synthesis also affect chemotaxis of human neutrophils . Doxycycline, but not lymecycline, initially decreased granulocyte adherence to glass surfaces . After 20 min of incubation granulocytes treated with both doxycycline and lymecycline adhered in higher numbers than control cells . Human leukocytes incubated with tetracycline hydrochloride or doxycycline in vitro showed a decreased capacity to phagocytize yeast and bacteria . Furthermore, leukocytes harvested from healthy volunteers after ingestion of tetracycline also demonstrated decreased phagocytic capacity . Scanning electron micrographic studies showed changed surface morphology for granulocytes incubated with tetracyclines, which might explain the changed adherence and phagocytosis by tetracycline-treated cells.

Acta Chir Scand Suppl, 1982, 508, 271 - 9
LOcal effects of antibacterial therapy (benzyl-penicillin) on missile wound infection rate and tissue devitalization when debridement is delayed for twelve hours; Dahlgren B et al.; Spherical steel bullets (0.88 g, 6.00 mm in diameter, impact velocity around 1000 m/s, smooth-bore rifle) were used for infliction of trauma to the thigh of pigs . The aim was to find out the effect of early antibiotic therapy (benzyl-penicillin) on wound infection rate and on the local progressive tissue devitalization when debridement was delayed until 12 hours after infliction of trauma . The main study on infection and tissue devitalization contained 20 missile wounds; the pilot study on cell metabolism 13 wounds . In the first group 11 pigs, and in the second group 7 pigs were treated with penicillin . Debridement was performed 12 hours after the infliction of trauma . Bacteriological analyses were done on tissue samples from the wound after pc treatment . The contents of adenosine triphosphate, creatine phosphate, glucose, glucose 6-phosphate and lactate were analysed in tissue samples from the wound with and without pc-treatment 12 h after trauma . The usual growth of bacteria when debridement was delayed for 12 h was totally inhibited by the early provision of penicillin . The amount of devitalized tissue-removed in relation to transferred energy was significantly reduced after the treatment as compared to the non-pc-group . The results of the studies on cell metabolism point to a graded tissue damage and possibly reversible injuries in the periphery of the wound, and to less metabolic disturbances after pc-treatment . The results indicated that early general supply of antibiotics may confine the local tissue injury when delayed debridement is anticipated.

Jpn J Antibiot, 1982 Jan, 35(1), 261 - 7
{Fundamental and clinical evaluations of cefmetazole against dermal infections by S . aureus (author's transl)}; Watanabe Y et al.; Fundamental and clinical studies were carried out to objectively evaluate the effectiveness and safety of cefmetazole (CMZ) in the treatment of S . aureus infections of the skin, and the following results were obtained . 1 . Blisters are induced with cantharis ointment to determine transfer of CMZ and cefazolin (CEZ) into the sclerosity and skin . The sensitivity of clinically isolated S . aureus was measured to these drugs . 2 . In case of CMZ, antibacterial activity, exudate and tissue transfer were favorable, and the sclerosity and skin concentration of the drug was such that it covered the major portion of MIC distribution of the clinically isolated S . aureus . 3 . In the crossover test following one shot intravenous injection of CMZ and CEZ at the doses of 1 g, drug concentrations in the serosity and skin were higher after CMZ as compared with those after CEZ . 4 . Clinical effect of this drug in the treatment of S . aureus infections of the skin in 10 cases was such that it was markedly effective in 4 cases, moderately effective in 4 and slightly effective in 2 cases . Bacteriological, effect of CMZ was eradication of the bacteria in 9 cases and change of bacterial flora in 1 case . In addition, the clinical effect of the drug in 2 cases in which cephalexin had been ineffective was that it was markedly effective in 1 and slightly effective in the other . 5 . Side effect was not observed in any of the treated cases . From the above, it was concluded that CMZ is highly useful drug in the treatment of S . aureus infections of the skin.

J Pediatr Gastroenterol Nutr, 1982, 1(3), 417 - 25
Intestinal bypass in the rat: a model for growth failure, liver disease, and jejunal bacterial overgrowth in marasmus and kwashiorkor; Maxwell JD et al.; The role of small intestinal bacterial colonisation on growth, liver function, and survival was examined in young rats, by comparing the effects of 90% small intestinal resection (resulting in nutritional disturbance from loss of absorptive surface) with equivalent small intestinal bypass (where the nutritional disturbance is accompanied by bacterial overgrowth in the long bypassed segment of jejunoileum) . Weight loss in bypass rats was double that seen in resected animals . This was not due to enhanced malabsorption, but was the result of reduced food intake . In addition, bypass rats developed hepatocellular dysfunction, the early onset of hypoproteinaemia (occasionally accompanied by ascites), and had high mortality . Adverse effects were due to bacterial overgrowth in the long excluded segment of small bowel, as they were modified by antibacterial drugs, and were not seen in rats with nutritional disturbance (resection) alone, which adapted well and had negligible postoperative mortality . Persistent bacterial overgrowth in the small intestine can adversely affect the host's appetite, growth, liver function, and survival . These abnormalities, which developed shortly after intestinal bypass in the rat, are reminiscent of marasmus and kwashiorkor, and suggest that bacterial overgrowth, rather than dietary deficiency, may be primarily responsible for the development of infant "malnutrition" in the developing world.

Antibiotiki, 1982, 27(7), 488 - 93
{Synthesis and properties of the N-ethyl derivatives of carminomycin and rubomycin}; Olsuf'eva EN et al.; N-Monoethyl derivatives of carminomycin, rubomycin, 13-dihydrocarminomycin and 13-dihydrorubomycin were synthesized by condensation of their amino groups with acetic aldehyde in the presence of sodium boron hydride . The respective N,N-diethyl derivatives of the antibiotics were formed as by-products of the reaction . New compounds such as N-ethylcarminomycin, N,N-diethylcarminomycin, N-ethyl-13-dihydrocarminomycin, N,N-diethyl-13-dihydrocarminomycin, N-ethylrubomycin and N-ethyl-13-dihydrorubomycin were synthesized . Antibacterial activity of N-ethyl- and N,N-diethyl derivatives of carminomycin and rubomycin determined with the use of Bac . mycoides as the test microbe was 40-50 per cent and that of N-ethyl- and N,N-diethyl-13-dihydro-derivatives was 15-30 per cent of the activity of the respective antibiotics, carminomycin and rubomycin.

Am J Vet Res, 1982 Jan, 43(1), 106 - 10
Effects of various treatments on induced chronic aflatoxicosis in rabbits; Clark JD et al.; Male New Zealand White rabbits were orally given 0.05 mg of aflatoxin B1 (AFB1)/kg of body weight daily for 10 days and were treated with glutathione-precursors and depletor, antibacterial agents, or sodium thiosulfate . The drug administered, the mortality, and the mean survival time were as follows: corn-oil controls (0), euthanatized at 25 days; AFB1-controls (2), 21 days; AFB1 and saline controls (2), 22 days; cysteine and AFB1 (5), 13 days; methionine and AFB1 (5), 12 days; sodium thiosulfate and AFB1 (2), 21 days; sulfadimethoxine and AFB1 (1), 24 days; oxytetracycline and AFB1 (0), euthanatized at 25 days; and ethyl maleate and AFB1 (3), 21 days . Clinical signs of toxicosis included decreased feed consumption during AFB1 administration, loss of body weight or failure to gain, and death . Clinicopathologic changes included increases in serum bilirubin concentration and alanine aminotransferase and aspartate aminotransferase activities . Prothrombin and activated partial thromboplastin times were lengthened . Plasma fibrinogen concentration was decreased . Changes in PCV, hemoglobin concentration, and serum alkaline phosphatase were unremarkable . Oxytetracycline had protective effects against chronic aflatoxicosis in rabbits . Cysteine and methionine enhanced chronic aflatoxicosis.

Graefes Arch Clin Exp Ophthalmol, 1982, 219(3), 131 - 4
Immunological studies on serpiginous choroiditis; Erkkila H et al.; Immunological studies on 15 patients with serpiginous choroiditis gave no definite indications of the aetiology of the choroidal vascular lesion which appears to be the initial failure in this disorder . On the basis of the patients' history, recurrencies, and clinical and fluorescein angiographic features, it was suspected that the disorder was of inflammatory origin, probably vasculitis due to an abnormal immune response . To some extent this was supported by the laboratory findings . Of the histocompatibility antigens, HLA-B7 was found more frequently than expected in a Finnish population (54.5% versus 24.3%; P less than 0.05) . Increased levels of antibacterial antibodies, ASO or ASTA, were found in eight patients and antiviral (herpes simplex) antibodies in two . One patient had earlier been treated due to positive syphilis serology, and one had an increased serum level of IgM as well as positive latex reaction in a dilution of 1:16 . The serum concentration of complement component C3 was slightly decreased in three of the six patients studied and at the lower limit of the normal range in one . No manifestations suggesting systemic disease were found.

Genetika, 1982, 18(8), 1231 - 5
{Effect of plasmid pKM101 on the mutagenic action of dioxidine in Escherichia coli K-12}; Bakai TS et al.; To define the types of base pair substitutions induced by the antibacterial agent dioxydine, the genotypes of Trp+ revertants of the trpA58 and trpA78 missense mutations were studied . Dioxydine was shown to induce transitions and transversions in the plasmidless strains, AT leads to GC transitions and, probably, GC leads to TA transversions exceeding other types of base changes . The strains harbouring pKM101 plasmid had the higher rate of mutations induced by dioxydine due to the increase in frequencies of AT leads to GC transversions and transitions of GC pairs . Thus, the mutator activity mediated by pKM101 results in a significant change in distribution of predominant types of dioxydine-induced base pair substitutions.

Arkh Patol, 1982, 44(7), 3 - 11
{Microphagal system in inflammatory and infectious processes}; Galankin VN et al.; The information accrued by now concerning disorders in polymorphonuclear leukocytes (PMNL) and the system of serum factors determining leukotaxis and PMNL bactericidal properties in inflammatory-infectious processes (IIP) of various origin is presented . Generalization of the available information suggests that IIPs develop not in the highest manifestations of the PMNL system phagocytic properties but not infrequently in the presence of its deficiency . The structurally-functionally undisturbed PMNL system favours good health . Disorders in the PMNL system are the structural-functional equivalent of clinical concepts: "reduced defence capacities of the host", "reduced nonspecific antibacterial resistance", etc . Sepsis is characterized by extreme disorders in the PMNL system.

Clin Ther, 1982, 5 Suppl A, 97 - 111
Update of safety of cefotaxime; Childs SJ et al.; Adverse reactions to various antibacterial drugs were compared in a review of the following: multiple-dose studies of cefotaxime (n = 3,463), cefazolin (n = 554), the combination gentamicin-clindamycin (n = 163), and cefoxitin (n = 18); prophylactic studies of cefotaxime (n = 300) and cefazolin (n = 149); and single-dose studies of cefotaxime (n = 314) and penicillin G procaine (n - 265) . The demographic and background characteristics of the groups were similar . Results of extensive pretreatment and posttreatment laboratory tests, measures of vital signs, and physical examinations revealed no clinically important intergroup differences . In the multiple-dose studies, side effects were reported in 9.8% of the cefotaxime, 3.8% of the cefazolin, 17.2% of the gentamicin-clindamycin, and 16.7% of the cefoxitin patients . The most frequent side effects were reactions at the injection site, of the skin and appendages, and of the digestive and urogenital systems, the only significant difference being fewer injection-site reactions in the cefazolin group than in the other three groups . In the prophylactic studies one cefotaxime patient reported rash and pruritus . In the single-dose studies, side effects were reported in 1.6% of the cefotaxime and 4.2% of the penicillin patients . Side effects sufficiently severe to warrant drug discontinuation were reported in 2.1% of the cefotaxime, 0.7% of the cefazolin, 1.8% of the gentamicin-clindamycin, and in none of the cefoxitin patients . Posttreatment prolongation of prothrombin time was found in one cefotaxime patient, whose pretreatment value was also abnormal, and in two gentamicin-clindamycin patients . No patient deaths were attributed to any of the drugs.

Chemotherapy, 1982, 28(5), 327 - 33
Study of the diffusion of cefotiam in the bronchial secretions; Bergogne-Berezin E et al.; The objective of this study was to evaluate the concentration in the bronchial secretions of a new injectable cephalosporin, cefotiam, which is characterized by an excellent antibacterial activity, stability against beta-lactamases and interesting pharmacokinetic properties . 30 patients suffering from acute exacerbation of a chronic bronchitis or bronchiectasis with expectoration, received either 1 g i . v . of cefotiam in a single dose or four doses of 1 g each over a period of 3 days . The bronchial secretion samples were obtained by fibroscopy, 1, 2, or 4 h after the last dose, in order to evaluate the kinetics of the bronchial concentration of cefotiam . Blood samples were taken simultaneously in order to establish a possible correlation between the bronchial and serum levels of the drug . The results of the study show a rapid and significant transfer of the drug through the bronchoalveolar capillaries, elevated bronchial concentrations starting from the 2nd h, reaching 10 micrograms/ml (or more) in certain cases, slow elimination with bronchial concentrations persisting at high levels for up to 4 h and a ratio between bronchial and serum concentrations of 25-60% at the 2nd h and more than 100% at the 3rd and 4th h . These results confirm the excellent diffusion of cefotiam, especially in the respiratory tract, allowing bronchial levels largely superior to the minimum inhibitory concentrations required to kill the bacteria usually responsible for lower respiratory tract infections.

Antibiotiki, 1982, 27(7), 507 - 11
{Separation and characteristics of the components of the antibiotic virenomycin}; Kudinova MK et al.; The composition of virenomycin, a new antitumor antibiotic was studied . Two components V and M were detected with high resolution liquid chromatography and thin layer chromatography on siluphol (Czechoslovakia) and silica gel (Merk, BRD) . A preparative method for separation of the antibiotic components with the use of chromatography on columns with silica gel was developed . Biological and physicochemical properties of separate components were studied to show that they significantly differed by their antibacterial action in vitro: virenomycin V was 2 to 4 times more active than virenomycin M against a number of microbes . The physicochemical properties of the components are similar . It was shown with mass spectrometry that the molecular weight of virenomycin is 12 units higher than that of virenomycin M . The PMR spectra showed that this difference is due to the presence of a vinyl group in the chromophore moiety of the virenomycin V molecule and a methyl group at the similar site of the virenomycin M molecule.

Infection, 1982, 10(2), 97 - 100
The cooperation of cefotaxime and desacetyl-cefotaxime with respect to antibacterial activity and beta-lactamase stability; Limbert M et al.; Desacetyl-cefotaxime, the main metabolite of cefotaxime, possesses a broad antibacterial spectrum . Its activity is lower than that of cefotaxime, but significantly surpasses that of cefazolin against gram-negative bacteria . The beta-lactamase stability of desacetyl-cefotaxime is higher than that of the parent compound . This beta-lactamase stability might be responsible for the synergistic effects of cefotaxime and desacetyl-cefotaxime occasionally seen in in vitro combination studies.

Infection, 1982, 10 Suppl 3, S204 - 8
{Antibiotic concentrations in the abdominal cavity as basis for antibacterial therapy of peritonitis: penetration of mezlocillin into the peritoneal exudate}; Wittmann DH et al.; The importance of the antibiotic concentration in peritoneal exudate is emphasized as a criterium for the possible success of antibiotic therapy of intra-abdominal infections . 5 g of mezlocillin were given i . v . over 15 min to ten patients with a mean age of 56 years . The serum concentrations, assayed microbiologically, were: 299.5 mg/l at the end of the infusion, 103.2 mg/l, 18.6 mg/l and 2.1 mg/l 60, 240 and 480 min after the end of the infusion, respectively . The serum half-life T1/2 beta, calculated from the beta phase, was 67 min . In the peritoneal fluid the peak concentration of Cp = 42.0 mg/l was achieved after 2.2 h . A quarter of this concentration was maintained in the peritoneal cavity for five to six hours . This concentration inhibited 74% of the 322 pathogens isolated from 123 intra-abdominal infections.

Infection, 1982, 10 Suppl 3, S199 - 200
{Mezlocillin concentrations in human lung tissue}; Kroening U et al.; The antibiotic concentrations were determined in 28 serum samples, 24 samples of lung parenchyma and 21 samples of the skeletal muscle from 28 patients who had undergone pneumonectomy . 5 g mezlocillin had been given i . v . as a bolus injection 30 to 150 minutes before sampling . The concentrations in the lung tissue were higher than the MICs for most bacteria for two hours . If a strain is less sensitive, a dose of more than 5 g is recommended . The concentrations in muscle tissue were also effective antibacterially.

Infection, 1982, 10 Suppl 3, S196 - 8
{Mezlocillin concentrations in the serum of children with impaired renal function}; Diekmann L et al.; Mezlocillin was administered as an intravenous bolus injection to eight children, aged 4-15, requiring antibiotic therapy; the dose was either 75 mg/kg or 37.5 mg/kg . All of the patients had advanced renal insufficiency . Five of the children required chronic intermittent hemodialysis . The microbiological method of Grove and Randall was used for the quantitative determination of mezlocillin in the serum . Ten minutes after the injection, the concentration of mezlocillin in the serum was approximately 90 mg/l and 40 mg/l, respectively . The determinations 30 and 60 minutes after the injection showed that the mezlocillin concentrations had fallen rapidly to approximately 30 mg/l and 20 mg/l, respectively . The mezlocillin concentrations were still approximately 2 mg/l and 1 mg/l, respectively, 12 hours after administration . For the period between 10 and 60 minutes, the half-lives were between 33 and 57 minutes . In general, we can conclude that a single bolus injection of 75 mg/kg will result in mezlocillin concentrations in the serum of uremic children which allow us to expect good antibacterial efficacy, at least for the first few hours following the injection . On the basis of our studies, half the dosage does not appear to be sufficient.

Infection, 1982, 10 Suppl 3, S138 - 40
Empiric antibiotic treatment of infections in myelosuppressed cancer patients . Preliminary results; Hellriegel KP et al.; A prospective, randomized study was performed to compare the efficacy and safety of mezlocillin plus sisomicin (Regimen A) and cefamandole plus tobramycin (Regimen B) . Sixty-one episodes of documented infections were treated in 49 adult myelosuppressed cancer patients . About two-thirds of the patients treated with either regimen responded to this antibacterial therapy . The patients failing to respond to the initial therapy were treated with additional antibiotics, either with the empiric Regimen C (cefotaxime plus amikacin plus azlocillin) or with antibiotics selected on the basis of bacteriological results (Regimen D) . With these schedules, the over-all response rate was increased to about 90% . The data suggest that febrile granulocytopenic cancer patients may profit from this empiric and sequential antibiotic treatment.

Infection, 1982, 10 Suppl 3, S125 - 7
Mezlocillin in serious surgical infections caused by carbenicillin-resistant bacteria; Lewandowski A et al.; Fifty-eight surgical patients suffering from severe bacterial infections caused by mezlocillin-sensitive, carbenicillin and/or gentamicin-resistant bacteria were treated with mezlocillin in 1980 . At the end of therapy, the infection had been eliminated in 52 patients; they were cured . The remaining six did not need any additional antibacterial treatment . Sixty-two of the bacterial strains isolated had been eliminated, seven markedly reduced in number and three persisted . No development of resistance or side-effects was observed . A randomized comparative study was conducted at the same time.

Boll Ist Sieroter Milan, 1982, 61(4), 300 - 8
{Microbiological evaluation of the antibacterial activity of cefotaxime in comparison with other cephalosporins}; Concia E et al.; In this study we have evaluated the antibacterial activity of six cephalosporins of the first generation (cephacetrile, cephalothin, cefazolin, cephaloridin, cephalexin, cephradine) two cephalosporin of the second generation (cefoxitin and cefuroxime) and two of the third generation (cefotaxime and cefoperazone) against 66 clinical bacterial isolates . Cefotaxime has been highly active against the strains examined in this study with low MICs.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1981 Dec, 174(6), 523 - 9
{Antibacterial efficacy of some gargles in vivo (author's transl)}; Hirschl A et al.; Commercially available gargles containing (hexetidin 0.1%, dequaliniumchloride 0.01%, benzydamin 0.15%) or not containing (OdolTM 0.5%) antibacterials as well as hydrogen-peroxide (3% ml/ml) and aqua dest . as a control tested for their antibacterial efficacy in vivo by applying them for 30 s . Standardized mouth- and throat-washings of 15 volunteers were examined for their aerobic viable counts before as well as 5 and 60 min after gargling . The 5-minutes values (tab . 1) indicated only hexetidin to reduce the oro-pharyngeal flora significantly though not very profoundly by 0.95 orders of magnitude . Usage of the other gargles caused only log reductions of 0.16 to 0.39, aqua dest . such of 0.23 . Sixty minutes after treatment (tab 2.) there was still a small but significant reduction of 0.61 log units demonstrable with hexetidin and the viable counts after treatment with hydrogen-peroxide were 0.31 log units below the baseline . The log reductions as assessed with the other gargles ranged 0.0 to 0.18 . It is concluded that the favourable therapeutic effects observed clinically with many "antiseptic" gargles with infections of the upper respiratory tract are not based on the antibacterial efficacy of such preparations.

Immunopharmacology, 1981 Dec, 3(4), 281 - 7
Effects of antibacterial agents on the complement system; Chakrabarty AK et al.; The alteration of serum complement profile following therapy with various antibiotics was studied in 23 hospitalized patients and in 10 human volunteers . Tetracycline, chloromycetin, ampicillin, and streptomycin reduced serum CH50 and C3 levels in the inpatients . Tetracycline administration for three consecutive days in four normal subjects decreased serum CH50, C1q, C3, and C4 levels on day 4 . However, these parameters returned to near-normal levels on day 7 following the withdrawal of the drugs . On the other hand, septran administered in six normal individuals for three consecutive days had no significant effect on the complement system . In vitro studies as well as in vitro studies in guinea pigs treated with various antibiotics showed almost parallel results.

Farmaco {Sci}, 1981 Dec, 36(12), 1004 - 18
{3-Methylthio-, 3-(amino-substituted)ethylthio-, 3-carboxymethylthio-, 3,3'-(dithiobis)-5-aryl-4H(R)-1,2,4-triazoles and 2-aminomethyl-N-substituted derivatives of 5-aryl-4H(R)-1,2,4-triazolin-3-thione: synthesis and biological activity}; Mazzone G et al.; Following previous research which showed the antibacterial and antimycotic activity of triazolin-3-thiones (II), a series of compounds has been prepared and tested to correlate and clarify the structure-activity relationships . The compounds were of the type represented in (II) where (R = H, CH3 or C6H5) and were in detail: 3-methylthiotriazoles (III-VIII), 3-(amino-substituted)ethylthiotriazolines (IX-XXVI), 3-carboxymethylthiotriazolines (XXVII-XXX), 3,3'dithiobistriazolines (XXXI-XXXVI) and 2-amino-methyl-N-substituted triazolin-3-thiones (XLVIII-LXVI) . The 2-aminooxadiazoles (XXXVII-XLII), obtained in place of the expected 1-aroyl-S-methylisothiosemicarbazides (II a) from the reaction between thiosemicarbazides (I) (R = H; CH3, C6H5) and methyl iodide, are also described.

J Inorg Biochem, 1981 Dec, 15(4), 349 - 57
Iron--dioxygen-dependent changes to the biological activities of bleomycin; Gutteridge JM et al.; Antitumor antibiotic bleomycin can bind to and degrade DNA, both in vivo and in vitro . This DNA damaging property in vitro can be related to its ability to chelate ferrous ions under aerobic conditions leading to the formation of "active oxygens," which are thought to be directly responsible for the damage . At present, evidence points to the hydroxyl radical formed by an iron-catalyzed Haber-Weiss reaction as the free radical most likely to be involved in this damage . When these same reactions occur in the absence of DNA, the free radicals then damage the bleomycin molecule, resulting in changes to its DNA-degrading activity, antibacterial properties, and chemical composition . Attempts to protect both bleomycin and DNA with a variety of specific and nonspecific scavengers have been unsuccessful, with several even showing pro-oxidant activity towards the iron-dependent damage . Only the metal chelators were effective inhibitors of bleomycin-iron-dependent damage to DNA . The damaged bleomycin lost some 50% of its ability to degrade DNA in vitro . This activity was closely paralleled by a loss in antibacterial activity against two different strains of bacteria.

Br J Clin Pharmacol, 1981 Nov, 12(5), 695 - 9
Peritoneal absorption of the antibacterial and antiendotoxin taurolin in peritonitis; Knight BI et al.; 1 Taurolin metabolite plasma concentrations were measured in two groups of patient undergoing abdominal surgery, one group with peritonitis and the other without peritonitis, each group receiving taurolin by intraperitoneal instillation . 2 There was no significant difference in the area under the curves, for the two groups, for one of the metabolites . This would suggest that the absorption of taurolin was not modified in inflammatory conditions such as bacterial peritonitis.

J Antibiot (Tokyo), 1981 Nov, 34(11), 1416 - 23
Studies on SF=1902 A2 A5, minor components of SF-1902 (globomycin); Omoto S et al.; Four members of globomycin, SF-1902 A2, A3, A4a and A4b were newly isolated from the culture of Streptomyces hygroscopicus SF-1902 . These minor components shared four amino acids in common and the fifth was either valine or allo-isoleucine . The fatty acid moiety varied from 3-hydroxy-2-methylheptanoic acid in A2 to 3-hydroxy-2-methylundecanoic acids in A4b . The length of alkyl chain greatly affected the antibacterial activity, and maximum activity was shown by the homologue (A5) possessing the longest alkyl chain.

J Med Chem, 1981 Nov, 24(11), 1314 - 9
Synthesis and antibacterial activity of 1-(arylamino)-1H-pyrroles and 4-(1H-pyrrol-1-ylimino)-2,5-cyclohexadienes; Johnson RE et al.; The syntheses of 1-(arylamino)-1H-pyrroles and 4-(1H-pyrrol-1-ylimino)-2-5-cyclohexadienes are described . Several of these compounds express in vitro antibacterial activity or can be metabolized to show in vitro antibacterial activity, and a few examples have shown efficacy against tuberculosis in mice . One compound, N,N'-(2,5-cyclohexadiene-1,4-diylidene)bis-1H-pyrrol-1-amine, is completely effective at 6.25 mg/kg against Mycobacterium tuberculosis H37Rv.

J Med Chem, 1981 Nov, 24(11), 1310 - 4
Synthesis and antibacterial activity of some ester, amides, and hydrazides of 3-carboxyrifamycin S . Relationship between structure and activity of ansamycins; Bellomo P et al.; Esters, amides, and hydrazides of 3-carboxyrifamycin S were synthesized by oxidizing the cyanohydrin of 3-formylrifamycin SV to 3-(cyanocarbonyl)rifamycin S, followed by treatment with alcohols, amines and hydrazines . The in vitro microbiological activity of the derivatives was quite low, especially toward Gram-negative bacteria . This poor activity was not shown to be due to the inadequate inhibiting action on the bacterial DNA-dependent RNA polymerase but to the poor penetration of the compounds through the bacterial cell wall . The microbiological activity was correlated to the chemical properties of the substituent on C3.

Am Fam Physician, 1981 Nov, 24(5), 107 - 13
Wound healing; Riley WB Jr; In acute wounds, there is no substitute for mechanical debridement and irrigation . Enzymes are useful in some chronic wounds, but antibacterial solutions are indicated only when gross contamination or frank purulence exists . Sutures will endure as the method of choice for precise wound closure . A moist environment and topical vitamin A appear to enhance epithelialization . Deficiencies of specific vitamins and minerals affect different aspects of repair, but excess levels do not accelerate healing . The biology of exuberant scars is a mystery, but management by pressure, steroids and surgery is often successful.

J Dent Res, 1981 Nov, 60(11), 1897 - 1903
Long-term antiplaque, anticalculus, and antigingivitis effects of benzethonium/polymer complex in beagle dogs; Gaffar A et al.; An electrostatic complex of 0.1% benzethonium chloride (BTC) plus 0.05% copolymer of methoxyethylene and maleic acid was evaluated in vitro for antibacterial effect . The complex by itself showed as much antibacterial activity as 0.1% BTC . The adsorption of 14C-BTC on saliva-coated hydroxyapatite disks and teeth in vitro was lower from the complex than the BTC solution, although in vivo activity was the same . The complex, BTC, and polymer solutions were evaluated in a 28-week study in 16 beagle dogs against plaque, gingivitis, and calculus formation . BTC and the complex significantly (alpha = 0.05) reduce plaque and gingivitis . There was no significant difference between the two active groups . BTC (0.1%) significantly increased calcified deposits at 22-28 wk compared to the water control group, while the complex and the polymer groups showed significantly (alpha = 0.05) less calculus . Thus, the complex was not only effective in vivo, but also significantly (alpha = 0.05) reduced tendencies of cationic antibacterials to induce calcified deposits on teeth.

Am J Vet Res, 1981 Nov, 42(11), 2010 - 3
Inhibitory effects of combinations of oxytetracycline, dimethyl sulfoxide, and EDTA-tromethamine on Escherichia coli; Wooley RE et al.; Antibacterial activity against Escherichia coli was obtained with subminimal inhibitory concentrations of oxytetracycline (OTC) and EDTA-tromethamine . Inhibitory effects were not observed using combinations of dimethyl sulfoxide and OTC or dimethyl sulfoxide and EDTA-tromethamine . Neither EDTA-tromethamine nor OTC used alone was capable of the same degree of inhibition . Using a 2-dimensional Microtiter checkerboard technique, the inhibitory activity of these combinations was studied and isobolograms were plotted . A synergistic effect was seen with combinations of OTC and EDTA-tromethamine . Kinetic studies of microbial death, using subminimal inhibitory concentrations of these agents, confirmed these findings.

Clin Orthop, 1981 Nov-Dec, (161), 154 - 62
Antibacterial and osteoinductive properties of demineralized bone matrix treated with silver; Kramer SJ et al.; The problems incurred by storage of demineralized bone allograft material and its potential use in contaminated operative sites make an antibacterial property desirable . Silver was considered for this role because of its wide spectrum of antibacterial susceptibility, low incidence of resistance, and its ability to persistently inhibit bacteria after binding to collagen matrices . Demineralized bone matrix prepared from rat diaphyseal bone segments was treated by exposure fo AgCl, AgNO3 and NaNO3 solutions prior to lyophilization . The resulting material was tested for bacterial inhibition after incubation in saline solutions for various times and showed inhibition persisting for at least four weeks (Ag-treated material only) . Silver treating the matrix was found to partially inhibit the osteoinductive capacity at 10(-3) and 10(-2) M but not at 10(-5) M as measured by intramuscular implantation in the rat for six weeks . Control and NaNo3-treated specimens showed normal bone growth as measured by ashing and by 99mTc binding, and confirmed by radiologic densities . Histologic sections showed dense microdeposits on dense material predominately near the decalcified bone surfaces, but also within the matrix . The results suggest that pretreatment with silver at concentrations in the 10(-4) range would render the implant material antibacterial, protect its sterility, and leave the osteoinductive capacity intact.

J Antibiot (Tokyo), 1981 Nov, 34(11), 1424 - 8
Oligostatins, new antibiotics with amylase inhibitory activity . I . Production, isolation and characterization; Itoh J et al.; Oligostatins C, D and E, three new antibiotics were found in the culture filtrate of Streptomyces myxogenes nov . sp . SF-1130 . Their spectral and chemical properties suggested that oligostatins were basic oligosaccharide antibiotics . They exhibited not only antibacterial activity but also strong amylase inhibitory activity.

Biochemistry, 1981 Oct 13, 20(21), 5981 - 7
Antibacterial peptide from normal rabbit serum . 2 . Compositional microanalysis; Carroll SF et al.; The composition and homogeneity of the primary bactericide (PC-III) isolated from normal rabbit serum were examined by microanalytical techniques . Dansylated acid hydrolysates of PC-III were analyzed by two-dimensional thin-layer chromatography on polyamide layers . Quantitation of the separated dansyl amino acids was achieved by elution into methanol, followed by determination of fluorescence in a filter fluorometer . The method proved inexpensive and reliable, allowing accurate analysis of peptide samples containing greater than 20 pmol of each amino acid . By use of this technique, an amino acid composition for PC-III is presented which suggests that the rabbit serum bactericide contains a single, 2000-dalton peptide composed of 17 amino acid residues, 24% basic and 35% nonpolar . One of the basic residues appears to be a modified amino acid, tentatively identified as N epsilon-methyllysine . Although small amounts of carbohydrate and lipid were also detected in PC-III by fluorescent and isotopic techniques, gel filtration or extraction with organic solvents removed much of this material without significantly affecting biological activity.

J Med Chem, 1981 Oct, 24(10), 1250 - 3
Synthesis and evaluation of ureido- and vinylureidopenicillins as inhibitors of intraruminal lactic acid production; Clark RD et al.; A series of 14 vinylureidopenicillins and a series of 9 ureidopenicillins were prepared by reaction of 6-aminopenicillanic acid with vinyl isocyanates and isocyanates . These compounds were evaluated for their potential to protect ruminants against lactic acidosis . The compounds were tested for inhibition of in vitro ruminal lactic and propionic acid production, and six compounds inhibited lactic acid production to less than 10% of control at doses of 0.31 microgram/mL or lower, whereas they did not inhibit propionic acid production at doses greater than 10 micrograms/mL . The most active compounds also were screened for general antibacterial activity and were found to be weakly active against Gram-positive bacteria . The structure--activity relationships are discussed for both series . Triethylammonium 6-{3{2-(4-tert-butylphenyl)vinyl}ureido}penicillanate (4) was chosen for evaluation as an inhibitor of intraruminal lactic acidosis in vivo.

J Med Chem, 1981 Oct, 24(10), 1245 - 9
Potential salicylamide antiplaque agents: in vitro antibacterial activity against Actinomyces viscosus; Coburn RA et al.; A series of 55 salicylamides, including 3,5-dibromo-, 5-n-alkyl-, and 5-n-acylsalicyloyl derivatives of various anilines, heterocyclic amines, benzylamines, and alkylamines, was synthesized and evaluated for in vitro antibacterial activity against Actinomyces viscosus, an adherent oral microorganism implicated in periodontal disease . The in vitro minimum inhibitory concentrations of 15 4'-bromosalicylanilides were found to correlate (r = 0.92) with estimated log D values . Several nonhalogenated salicylanilides, such as 5-n-hexyl- (40) and 5-n-decanoyl-4'-nitrosalicylanilide (47), were found to exhibit higher levels of in vitro antibacterial activity against a number of Actinomycetes than did tribromsalan (1) or fluorophene (2).

Pol J Pharmacol Pharm, 1981 Oct, 33(3), 359 - 63
Quantitative structure-activity relationships in erythromycin group with MTD technique; Bojarska-Dahlig H et al.; Quantitative structure-activity correlation studies were performed for a group of 17 erythromycin derivatives modified in the C-8--C-12 portion of the molecule . The minimal steric difference, MTD, was used as the structural parameter and logarithm of the biological potency measured by a standard assay, as the biological parameter . The influence of the sp2 hybridization at C-9 and of the presence of 11, 12-carbonate grouping on the antibacterial activity was shown . The reported results give a further support to our hypothesis on greater complementarity of the cyclic 11, 12-carbonates in the reaction on the bacterial ribosomes in comparison with their parent antibiotics.

J Antibiot (Tokyo), 1981 Oct, 34(10), 1290 - 9
Studies on beta-lactam antibiotics . II . Synthesis and structure-activity relationships of alpha-hydroxyiminoarylacetyl cephalosporins; Takaya T et al.; The synthesis and antibacterial activity in vitro of the 2-aryl-2-hydroxyiminoacetyl cephalosporins (2) are described . Within this cephalosporin series, analogs (9f approximately 13f) with 2-hydroxyimino-2-(3-hydroxyphenyl)acetyl group at the 7-position of a cephem nucleus were found to have the highest antibacterial activity against a wide-range of microorganisms, including beta-lactamase-producing bacteria . Structure-activity relationships of 2 are discussed.

Am J Med, 1981 Oct, 71(4), 571 - 7
Invasive aspergillosis . Progress in early diagnosis and treatment; Fisher BD et al.; Ninety-one patients with documented invasive infections due to an Aspergillus species were identified at Memorial Sloan-Kettering Cancer Center from July 1, 1971, through December 31, 1976 . Of the 29 patients in whom the diagnosis was made during life, 10 had successful treatment and survived the Aspergillus infection by two to 17 months . An immunodiffusion test was useful in the early diagnosis of invasive aspergillosis, and in 11 patients in whom the diagnosis was supported by seroconversion and who underwent treatment, the survival rate was 64 percent . Cultures of respiratory secretions were not reliable because they often reflected only colonization . In one year, only 9 percent of he patients with Aspergillus species isolated from the sputum had an invasive infection . The lung was the commonest site of involvement, 91 percent of the patients having pulmonary lesions . The most frequently affected extrapulmonary organ was the brain (18.3 percent) . Eight patients had nonpulmonary aspergillosis as the only manifestation of this infection . Most of the 91 patients had hematologic neoplasms as the underlying disease, and neutropenia and antibacterial therapy preceded the diagnosis of aspergillosis in the majority of cases.

Antimicrob Agents Chemother, 1981 Oct, 20(4), 470 - 6
Antibacterial properties of alafosfalin combined with cephalexin; Atherton FR et al.; The phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) exhibited synergy in vitro and in animal studies against a range of bacterial genera when combined with cephalexin . Alafosfalin also showed synergy with mecillinam and, to a much lesser extent, with ampicillin . Synergy with cephalexin was more pronounced when the bacteria were relatively insensitive to the beta-lactam component . The action of this combination involved both an inhibitory and a bacteriolytic mechanism which was abolished by concurrent treatment with the aminopeptidase inhibitor, bestatin . Regrowth of subpopulation resistant to either component was markedly reduced by the combination . The potential of alafosfalin combined with cephalexin for use in therapy is discussed.

Zh Mikrobiol Epidemiol Immunobiol, 1981 Oct, (10), 33 - 8
{Use of live Flexner 2a 516M dysentery vaccine for the immunotherapy of acute and chronic dysentery}; Sultanov GV et al.; Live dysentery vaccine prepared from Sh . flexneri 2a 516 M, a spontaneous mutant, was used for the treatment of 153 patients with acute and chronic dysentery . A single oral administration in a dose of 25 X 10(9) live microbial cells and 2 oral administrations in doses of 25 X 10(9) and 50 X 10(9) live microbial cells did not induce the clinical aggravation of the disease, greatly reduced the time of the reparation of the intestinal mucosa and reduced the frequency and duration of excretion of the infective agent by patients with acute and chronic dysentery, as well as considerably enhanced the levels of IgG, IgM and particularly IgA in the blood and saliva of the vaccinees in comparison with the controls . These data indicate that live dysentery vaccine, when used for the immunotherapy of dysentery, possesses high immunological and antibacterial effectiveness.

Proc Natl Acad Sci U S A, 1981 Oct, 78(10), 6324 - 8
Structured habitats and the evolution of anticompetitor toxins in bacteria; Chao L et al.; We demonstrate that in liquid cultures, defined in this study as a mass habitat, the outcome of competition between Escherichia coli that produce an antibacterial toxin (colicin) and sensitive E . coli is frequency dependent; the colicinogenic bacteria are at an advantage only when fairly common (frequencies in excess of 2 X 10(-2)) . However, we also show that in a soft agar matrix, a structured habitat, the colicinogenic bacteria have an advantage even when initially rare (frequencies as low as 10(-6)) . These contrasting outcomes are attributed to the colicinogenic bacteria's lower intrinsic growth rate relative to the sensitive bacteria and the different manner in which bacteria and resources are partitioned in the two types of habitats . Bacteria in a liquid culture exist as randomly distributed individuals and the killing of sensitive bacteria by the colicin augments the amount of resource available to the colicinogenic bacteria to an extent identical to that experienced by the surviving sensitive bacteria . On the other hand, the bacteria in a soft agar matrix exist as single-clone colonies . As the colicinogenic colonies release colicin, they kill neighboring sensitive bacteria and form an inhibition zone around themselves . By this action, they increase the concentration of resources around themselves and overcome their growth rate disadvantage . We suggest that structured habitats are more favorable for the evolution of colicinogenic bacteria.

J Antibiot (Tokyo), 1981 Oct, 34(10), 1318 - 26
A set of bacterial strains for evaluation of beta-lactamase-stability of beta-lactam antibiotics; Sawai T et al.; A set of bacterial strains composed of nine bacterial groups, with each made up of three or four strains, was used to estimate the stability of beta-lactam antibiotics to nine types of beta-lactamases from Gram-negative bacteria . The strains in the same group produced the same kind of enzyme constitutively, but the enzyme activity achieved in the bacterial cell differed with different strains . The difference in antibacterial activity of each antibiotic on the strains of each group, easily measured by a simple plate technique, permits an estimation of its relative stability to each beta-lactamase . This method was applied to thirteen beta-lactam antibiotics including seven new ones.

J Toxicol Environ Health, 1981 Oct, 8(4), 639 - 48
Effects of chlorinated bisphenols on torula yeast glucose-6-phosphate dehydrogenase; Wang JL et al.; Chlorinated bisphenol antibacterial and antifungal agents are potent inhibitors of torula yeast glucose-6-phosphate dehydrogenase (G6PD) . Several compounds were tested, including hexachlorophene {HCP; 2,2'-methylenebis(3,4,6-trichlorophenol)}; 2,2'-oxybis(tetrachlorophenol); 2',4-dihydroxy-2,3,3',5,5',6-hexachlorodiphenylmethane; 2,2'-methylenebis(3,4-dichlorophenol) (3,4-TCP); bithionol {2,2'-thiobis(4,6-dichlorophenol)}; 2,2'-methylenebis(3,5-dichlorophenol); 2,2'-dihydroxy-3,3',5,6,6'-pentachlorodiphenylmethane; 2,2'-methylenebis(4-chlorophenol) (DCP); 2,2'-methylenebis(4,6-dichlorophenol); and the related uncoupler 2,4-dinitrophenol . The relative inhibitory activity of the chlorinated bisphenols tended to increase with degree of chlorination of the aromatic rings . the concentrations of the bisphenols that caused 50% inhibition ranged from 2.5 micrometers for 2,2'-oxybis(tetrachlorophenol) to 40 micrometers for 2,2'-methylenebis(4,6-dichlorophenol) under comparable assay conditions . More detailed kinetic analysis showed that, as with HCP, the inhibition of G6PD by 3,4-TCP and DCP followed noncompetitive kinetics . Calculations from the kinetic data gave apparent inhibition constant (Ki) values for 3,4-TCP of 267 micrometers with G6P and 308 micrometers with NADP, and for DCP of 697 micrometers with both G6P and NADP.

J Biochem (Tokyo), 1981 Oct, 90(4), 1087 - 91
Adsorption of 14C-labeled gramicidin S on cell of bacteria; Yonezawa H et al.; Gramicidin S (GS) containing 14C-labeled proline was synthesized by a solid-phase method, and the labeled GS dihydrochloride was obtained as crystals . The labeled GS exhibited same antibacterial activity as natural GS . Strains sensitive to GS (B . subtilis and S . aureus) and an insensitive strain (E . coli) were treated with the labeled GS, and the amount of the labeled GS adsorbed on the cells was measured . GS was adsorbed rapidly on the cells of the sensitive strains; the amount adsorbed increased linearly with GS concentration up to 1-1.5 microgram/ml, and at a lower rate at above 1.5 microgram/ml . GS molecules covered most of the cell surface at the minimum inhibitory concentration of 1.5 microgram/ml; the number of molecules adsorbed per cell was 1.3-1.4 x 10(6) . No GS was adsorbed by the insensitive strain.

J Antibiot (Tokyo), 1981 Sep, 34(9), 1152 - 6
Preparation and biological activities of 10-decarbamoyloxy-9-dehydromitomycin B and its analogs; Urakawa C et al.; A new naturally occurring mitomycin, 10-decarbamoyloxy-9-dehydromitomycin B (1), was prepared by treating mitomycin B with sodium hydride . Its analogs having an exo-cyclic double bond in their structure were also synthesized . These compounds showed antibacterial and cytotoxic activities . Among them, 7-amino-10-decarbamoyloxy-9-dehydro-7-demethoxymitomycin B (2) was the most potent growth inhibitor of KB cells in vitro and, accordingly, it appears to be a potential antitumor agent.

Infect Immun, 1981 Sep, 33(3), 775 - 8
Increased content of microbicidal cationic peptides in rabbit alveolar macrophages elicited by complete Freund adjuvant; Lehrer RI et al.; We measured the microbicidal peptides MCP-1 and MCP-2 in rabbit alveolar macrophages (AM), comparing rabbits pretreated with complete Freund adjuvant with untreated control animals . Levels of MCP-1 increased from 4.7 +/- 0.6 microgram/10(7) resident AM to 13.2 +/- 0.1 microgram/10(7) complete Freund adjuvant-elicited AM . MCP-2 levels rose from 1.8 +/- 0.1 microgram/10(7) resident AM to 7.3 +/- 0.4 microgram/10(7) complete Freund adjuvant-elicited AM . The activities of five lysosomal hydrolases (beta-D-glucuronidase, beta-D-galactosidase, acid phosphatase, N-acetyl-beta-D-galactosaminidase, and N-acetyl-beta-D-glucosaminidase) were 44 to 96% higher in complete Freund adjuvant-elicited AM, and lysozyme activity was three- to fourfold higher . As MCP-1 and MCP-2 are major constituents of rabbit AM and exhibit potent antibacterial and antifungal properties, they may contribute to the expression of microbicidal activity in both resident and activated states.

Urology, 1981 Sep, 18(3), 273 - 6
Heparin--examination of its antibacterial adsorption properties; Hanno PM et al.; One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of inoculated bacteria . Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this "antiadherence factor." To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy . Protamine offered no protection against bacterial adherence in the rabbit model . It appears that heparin's protective effect is unrelated to its action as an anticoagulant.

Antimicrob Agents Chemother, 1981 Sep, 20(3), 344 - 50
Aminoglycoside phosphotransferase-II-mediated amikacin resistance in Escherichia coli; Bongaerts GP et al.; An Escherichia coli strain with a plasmidic amikacin resistance has been selected for which the evidence strongly indicates that resistance is mediated by aminoglycoside phosphotransferase {APH(3')-II}: (i) this resistance was coupled with resistance against kanamycin and neomycin; (ii) partially purified APH(3')-II{APH(3") free} modified amikacin by phosphorylation; (iii) the product of the APH(3')-II mediated reaction (i.e., 3'-O-phosphoryl-amikacin) lost its antibacterial activity; and (iv) the amikacin-modifying APH(3')-II activity increased 5- to 10-fold after adaptation of the cells to higher concentrations of amikacin . The substrate spectrum of this enzyme showed a low activity against amikacin as compared with neomycin . It is argued that the enzyme level rather than its substrate spectrum is important for enzyme-mediated resistance . The increase in enzyme levels was found to be correlated with an increase in copy number of a 110-Megadalton plasmid (pBN66) which coded for the APH(3')-II and the APH(3") activity . The increase in copy number was irreversible, and therefore this phenomenon is ascribed to a mutation of a gene which affects the copy number . In transconjugants, the original low copy number was present, and therefore the mutation must be located on the chromosome and not on the plasmid.

Gastroenterology, 1981 Sep, 81(3), 584 - 91
Intestinal cryptosporidiosis complicated by disseminated cytomegalovirus infection; Weinstein L et al.; A 48-yr-old man with profuse diarrhea for about 9 mo was found to have intestinal cryptosporidiosis . Treatment with antibacterial, antimalarial, and other antiprotozoal agents failed to control the disease . The organisms were identified by light and electron microscopy in a biopsy specimen from the duodenum . Disseminated infection with cytomegalovirus developed during treatment, and the patient died . Five other instances of intestinal cryptosporidiosis have been reported . Immunologic incompetence, related to either disease or therapy, or both, was present in 4 cases but, although suspected, could not be proved in the patient described in this paper.

J Med Chem, 1981 Aug, 24(8), 1001 - 3
Folate antagonists . 19 . Synthesis and antimalarial effects of 6-(arylthio)-2,4-pteridinediamines; Elslager EF et al.; A series of 6-(arylthio)-2,4-pteridinediamines (IIIa) was prepared by allowing 6-chloro-2,4-pteridinediamine to react with the requisite benzenethiols in dimethyl sulfone at 190-200 degrees C . Attempts at oxidation to the corresponding sulfoxide (IIIb) or sulfone (IIIc) were unsuccessful . The compounds exhibited a spectrum of antibacterial activity similar to, but below the potency of, the related quinazolinediamines and pteridinediamines . Unlike these related types, however, they were devoid of antimalarial activity when tested against a normal drug-sensitive strain of Plasmodium berghei in mice by the parenteral route.

J Antibiot (Tokyo), 1981 Aug, 34(8), 1011 - 8
Acyl derivatives of 16-membered macrolides . II . Antibacterial activities and serum levels of 3"-O-acyl derivatives of leucomycin; Sakakibara H et al.; 3"-O-Acylation of leucomycin A5 increased its in vitro antibacterial activity against sensitive microorganisms and also some resistant ones . An increased effect was particularly noted when an acetyl or propionyl group was introduced . On the contrary, acylation of the C-3 and C-9 hydroxyl groups reduced the antibacterial activity in vitro . Introduction of an acyl group at the C-3" hydroxyl group increased the serum level of the compound . The increase in serum level from 3"-O-acylation is higher than that from 3-O-acylation . The serum level of the 3"-O-propionyl derivative of leucomycin A5 was higher than that of the 3"-O-acetyl derivative . 3"-O-Propionylleucomycin A5 (5) was the derivative that showed the highest antibacterial activity and yielded the highest serum level among the derivatives examined.

J Antibiot (Tokyo), 1981 Aug, 34(8), 1001 - 10
Acyl derivatives of 16-membered macrolides . I . Synthesis and biological properties of 3"-O-propionylleucomycin A5 (TMS-19-Q); Sakakibara H et al.; Using leucomycin A5 (1), 3"-O-propionylleucomycin A5 (7) was synthesized by the following synthetic route: 2"-O-acetylation, 3,9-di-O-trimethylsilylation, 3"-O-propionylation, 3,9-di-O-detrimethylsilylation and 2'-O-deacetylation . Acylation of the 3"-tertiary hydroxyl group of 2'-O-acetyl-3,9-di-O-trimethylsilylleucomycin A5 with propionyl chloride in the presence of tribenzylamine at 70 degrees C gave a 3"-O-propionyl derivative in 96% yield . The structure of the final compound, 3"-O-propionylleucomycin A5 (7) was confirmed by means of mass, 1H-NMR and 13C-NMR spectrometry and chemical degradations . 3"-O-Propionylleucomycin A5 (7) showed higher antibacterial activity in vitro and higher serum levels than its mother antibiotic . The biological properties of 7 also were compared with those of josamycin and midecamycin.

J Clin Pharmacol, 1981 Aug-Sep, 21(8-9 Suppl), 283S - 291S
Biological activity of cannabichromene, its homologs and isomers; Turner CE et al.; Cannabichromene (CBC) is one of four major cannabinoids in Cannabis sativa L . and is the second most abundant cannabinoid in drug-type cannabis . Cannabichromene and some of its homologs, analogs, and isomers were evaluated for antiinflammatory, antibacterial, and antifungal activity . Antiinflammatory activity was evaluated by the carrageenan-induced rat paw edema and the erythrocyte membrane stabilization method . In both tests, CBC was superior to phenylbutazone . Antibacterial activity of CBC and its isomers and homologs was evaluated using gram-positive, gram-negative, and acid-fast bacteria . Antifungal activity was evaluated using yeast-like and filamentous fungi and a dermatophyte . Antibacterial activity was strong, and the antifungal activity was mild to moderate.

J Med Chem, 1981 Aug, 24(8), 933 - 41
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents . 5 . 3',5'-Dimethoxy-4'-substituted-benzyl analogues of trimethoprim; Roth B et al.; Forty trimethoprim analogues in which the para substituent in the benzene ring was varied were prepared for antibacterial evaluation . All were very potent inhibitors of Escherichia coli dihydrofolate reductase . The similarity of their inhibitory activities strongly suggested that the side chains beyond the first two atoms were not in contact with the enzyme . However, among 38 ether derivatives which varied widely in their bulk and lipophilicity, very few approached trimethoprim in their broad-spectrum in vitro antibacterial activity . The 4'-methyl and 4'-ethyl analogues and the allyloxy and gamma-chloropropoxy ethers had activities fairly close to that of trimethoprim . The two ethers were chosen for further evaluation in vivo . Neither compound quite matched trimethoprim in efficacy in mice, and their half-lives, as well as that of the beta-methoxyethoxy analogue, were found to be shorter in dogs.

J Clin Periodontol, 1981 Aug, 8(4), 338 - 48
Serum neutralizing activity against Actinobacillus actinomycetemcomitans leukotoxin in juvenile periodontitis; Tsai CC et al.; A relatively high incidence of infection by Actinobacillus actionomycetemcomitans can be shown in subgingival plaque samples obtained from patients with juvenile periodontitis . These organisms possess a potent leukotoxin(s) which rapidly destroys isolated human polymorphonuclear leukocytes (PMNs) and monocytes . If such leukotoxins operate in vivo, they could deprive the gingival crevice area of an essential antibacterial defense mechanism . We have found that sera from juvenile periodontitis patients consistently (greater than 90%) contain antibodies which neutralize Actinobacillus actinomycetemcomitans leukotoxin(s) . On the other hand, sera from normal individuals or patients with other types of periodontal disease usually amplified rather than inhibited the leukotoxic reaction . Many patients with juvenile periodontitis have demonstrable defects in PMN or monocyte chemotaxis and this may place them at risk to gingival infection by Actinobacillus actinomycetemcomitans . The immune response against these organisms could be a crucial determinant in the course of juvenile periodontitis . While this disease is relatively rare, it does cause immeasurable emotional, physical and economic hardship for patients and their families . The identification of Actinobacillus actinomycetemcomitans as a potential pathogen in this disorder may eventually lead to specific forms of therapy to prevent and eliminate infection by this organism in these patients.

Int J Pept Protein Res, 1981 Aug, 18(2), 127 - 34
Studies of peptide antibiotics . XLI . Syntheses of 6-L-valine-tyrocidine A and 7-L-ornithine-tyrocidine A; Kosui N et al.; Tyrocidine A (TA) is an antibiotic cyclic decapeptide with the sequence of cyclo (-L-Val1-L-Orn2-L-Leu3-D-Phe4-L-Pro5-L-Phe6-D-Phe7-L-Asn8-L-Gln9-L-Tyr10-) . Gramicidin S (GS) regarded as a homolog of TA is also a cyclic decapeptide with the sequence of cyclo (-L-Val1-L-Orn2-L-Leu3-D-Phe4-L-Pro5-L-Val5-L-Orn7-L-Leu8-D-Phe9-L-Pro10-) . GS shows higher antibacterial activity, whereas TA exhibits inhibitory activity on the biosynthesis of RNA . Two analogs of TA, {L-Val6}-TA (12a) and {L-Orn7}-TA (12b), were synthesized by the conventional method in order to study the interrelationships between the two related antibiotics TA and GS . Antibacterial activities of 12a and TA are nearly the same, but the activity of 12b is significantly lower . The optical rotatory dispersion spectra of 12a, 12b, and TA showed a trough at 233 nm region; the troughs of 12a and TA are nearly the same in depth, but the trough of 12b is shallower . Relationships between structure and activity of 12a and 12b compared with TA and GS were discussed.

Blood, 1981 Aug, 58(2), 221 - 7
The in vitro effects of Newcastle disease virus on the metabolic and antibacterial functions of human neutrophils; Faden H et al.; Live Newcastle disease virus (NDV) was used to investigate the in vitro effects of a viral infection on phagocytosis, chemiluminescence generation, superoxide production, oxygen consumption, NADPH-oxidase activity, and intracellular killing of bacteria by Ficoll-Hypaque separated human neutrophils . Phagocytosis of oil red O particles by NDV-treated PMN was inhibited by 50% . Chemiluminescence by PMN was inhibited 79% after zymosan stimulation and 86% after tetradeconyl phorbol acetate stimulation . Superoxide generation was inhibited by 68% . Oxygen consumption was inhibited in the presence of NDV by 37% after stimulation with phorbol myristate acetate, while membrane-associated NADPH-enzyme activity was decreased by 19% . The percent of surviving intracellular S . aureus was significantly elevated in NDV-treated PMN after 60 and 120 min of incubation . Purified bacterial neuraminidase markedly suppressed chemiluminescence, while neuraminic acid blocked the effects of the virus . These observations suggest that infections with myxoviruses may suppress a number of vital neutrophil functions . It appears that the effects may be partly mediated by the interaction of viral neuraminidase with the external neutrophil membrane.

Biochim Biophys Acta, 1981 Jul 27, 654(2), 279 - 86
Kinetics of dissociation of quinoxaline antibiotics from DNA; Fox KR et al.; The kinetics of detergent-induced dissociation of triostins A and C and quinomycin C from DNA have been investigated . All three antibiotics dissociate from poly(dA-dT) and poly(dG-dC) in a simple first-order fashion whereas their dissociation from a natural DNA (calf thymus) is complex, requiring three exponential terms for its complete description . This behaviour is attributed to sequence-selectivity on the part of the drugs and seems to represent dissociation from different classes of intercalative binding site . The time constants of dissociation are better resolved for quinomycins than for triostins, consistent with the view that quinomycins are more sequence-specific in their interaction with DNA, but it is not possible to identify any class of binding site with the alternating purine-pyrimidine sequences of the synthetic polydeoxynucleotides . In general, the triostins dissociate an order of magnitude faster than the corresponding quinomycins . This is attributable to a larger entropy of activation, presumably reflecting greater flexibility of the octapeptide ring when the cross-bridge is a disulphide as opposed to the slightly shorter thioacetal found in quinomycins . The longest time constant in the dissociation of each of the four quinoxaline antibiotics from calf thymus DNA correlates well with its antibacterial potency, in agreement with the conclusion that the biological effects result from impairment of the role of DNA as a template for polymerase activity.

Nature, 1981 Jul 16, 292(5820), 246 - 8
Sequence and specificity of two antibacterial proteins involved in insect immunity; Steiner H et al.; Immune responses have been described for many different insect species . However, it is generally acknowledged that immune systems must therefore differ from those of vertebrates . An effective humoral immune response has been found in pupae of the cecropia moth, Hyalophora cecropia . The expression of this multicomponent system requires de novo synthesis of RNA and proteins and its broad antibacterial activity is due to at least three independent mechanisms, the most well known of which is the insect lysozyme . However, this enzyme is bactericidal for only a limited number of Gram-positive bacteria . WE recently purified and characterized P9A and P9B, which are two small, basic proteins with potent antibacterial activity against Escherichia coli and several other Gram-negative bacteria . We believe that P9A and P9B plays an important part in the humoral immune responses described previously and that the P9 proteins represent a new class of antibacterial agents for which we propose the name cecropins . We describe here the primary structures of cecropins A and B . We also show that cecropin A is specific for bacteria in contrast to melittin, the main lytic component in bee venom which lyses both bacteria and eukaryotic cells.

Med J Aust, 1981 Jul 11, 2(1), 24 - 7
High-dose co-trimoxazole and its penetration through uninflamed meninges; Goodwin CS et al.; Normal doses of co-trimoxazole (two ampoules or two tablets twice a day) gave low cerebrospinal fluid concentrations of trimethoprim and sulphamethoxazole in neurosurgical patients . For two years, four ampoules of co-trimoxazole twice a day, followed by four tablets twice a day, which were administered to neurosurgical patients and to patients admitted to hospital with skull fractures, produced no toxicity and this regimen has not been associated with postoperative meningitis . After the high-dose regimen in patients with uninflamed meninges, trimethoprim concentrations in the cerebrospinal fluid ranged from 2.6 mumol/L to 12.4 mumol/L (0.75 mg/L to 3.6 mg/L), and in the serum from 9.6 mumol/L to 42.7 mumol/L (2.8 mg/L to 12.4 mg/L) . However, the bacteriostatic and bactericidal activities of the spinal fluids and sera were very variable, some with high concentrations appearing to have negligible antibacterial activity in vitro . We have treated a few patients with serious infections with dosages of 12 ampoules or 12 tablets twice a day with successful results . Studies of serum folate, 5-methyltetrahydrofolate and granulocyte dihydrofolate reductase levels showed no toxic effects from the high-dose regimen.

J Antibiot (Tokyo), 1981 Jul, 34(7), 800 - 10
Water-soluble siomycin-A derivatives . Preparation, chemical structures and biological properties of half-esters of the peptide antibiotic; Tokura K et al.; The peptide antibiotic siomycin-A was transformed into half-esters with dicarboxylic acids with the intention of making siomycin-A soluble in water . Sodium salts of the half-esters were also prepared . Some of the salts showed antibacterial activities comparable to siomycin-A against Gram-positive bacteria in vitro and exhibited better therapeutic effects in infected mice than siomycin-A . The chemical structures of siomycin-A hemiadipate-II and -III were elucidated by comparing their 13C and 1H NMR spectra with those of siomycin-A . Their physicochemical properties are described.

Farmakol Toksikol, 1981 Jul-Aug, 44(4), 473 - 6
{Role of the adrenals in the detoxication of dioxidine}; Gus'kova TA et al.; An original antibacterial drug dioxidine was subjected to toxicological studies during long-term parenteral administration of 0.5% solution to rats and guinea-pigs (in doses of 25-100 mg/kg) . It was found that susceptibility to the drug correlated well with adrenal function . Guinea-pigs were more susceptible to dioxidine than rats . The data obtained indicate the existence of the interplay between non-specific resistance to toxic agents and glucocorticoid potency.

J Antibiot (Tokyo), 1981 Jun, 34(6), 691 - 700
Substances derived from 4-de-N-methylfortimicin B; Kurath P et al.; The preparation of 4-de-N-methylfortimicin A analogs as well as the preparation of 4-de-N-methyl-4-N-(beta-aminoethyl)-4-N-ethylfortimicin B is reported . It was shown that the 4-N-methyl group in fortimicin analogs is essential for antibacterial activity since neither the 4-de-N-methylfortimicin A nor the 4-de-N-methyl-4-N-(beta-aminoethyl)-4-N-ethylfortimicin B exhibited useful biological activity.

J Antibiot (Tokyo), 1981 Jun, 34(6), 628 - 36
Epithienamycins-novel beta-lactams related to thienamycin . I . Production and antibacterial activity; Stapley EO et al.; The epithienamycins are cell wall active antibiotics structurally related to N-acetylthienamycin . We have found forty-three isolated of Streptomyces flavogriseus which are capable of producing members of the epithienamycin family . Six major epithienamycin components, and xanthomycin, have been isolated from fermentation broth . Fermentation conditions can be varied to enrich for certain members of the epithienamycin family . All six components show activity in vitro versus a broad spectrum of bacterial species . The weight potencies vary 27 fold from the most active to least active.

Toxicol Lett, 1981 Jun-Jul, 8(4-5), 229 - 34
Adrenocortical degeneration in dogs, monkeys, and rats treated with alpha-(1,4-dioxido-3-methylquinoxalin-2-YL)-N-methylnitrone; Yarrington JT et al.; The antibacterial compound alpha-(1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM), which was administered for a maximum period of 90 days, was given orally at 0, 7.5, 15.0 or 22.5 mg/kg/day for dogs; 0, 15, 50 or 100 mg/kg/day for rats; and 35 mg/kg/day for monkeys . Reduced food consumption and weight gain, depression, debility, and deaths occurred starting at doses (mg/kg/day) of 15 in dogs, 35 in monkeys and 50 in rats . Frequent emesis and occasional black, tarry feces were also observed in most treated dogs . Necropsy examinations revealed small, pale adrenal glands in rats given a dose of 50 mg/kg/day and gastrointestinal hemorrhage in dogs administered 15.0 or 22.5 mg/kg/day of DMNM . Microscopically, vacuolar degeneration of the canine, monkey and rat adrenal cortex was seen at all dosages and appeared to progress from the zona reticularis to the zona glomerulosa . In rats treated with 50 mg/kg/day of the drug chronic lesions of adrenal cortical fibrosis, atrophy, and nodular hyperplasia were also detected . The only other significant microscopic lesions consisted of mild testicular atrophy and occasional gastric erosions in dogs treated with 7.5 mg/kg/day of DMNM.

Biull Eksp Biol Med, 1981 Jun, 91(6), 708 - 9
{Immunobiologic study of the role of heterogenetic antigens of uropathogenic strains of E . coli}; Podoplelov II et al.; Analysis of 140 strains of E . coli isolated from patients with pyelonephritis has demonstrated heterogeneous antigens (in 44.3% of cases) related to ABO antigens against human red blood cells . 0(H)-like antigen occurred most frequently . The data obtained suggest that the presence of heterogeneous antigens in E . coli is associated with the formation of a latent subclinical form of pyelonephritis and with the decrease titers of antibacterial antibodies in patients.

Antimicrob Agents Chemother, 1981 Jun, 19(6), 1067 - 9
Activity of ceftazidime (GR 20263) against nosocomially important pathogens; Hamilton-Miller JM et al.; Ceftazidime was considerably more active than cefuroxime against 180 strains of resistant species of nosocomial gram-negative bacteria . In terms of antibacterial spectrum and intrinsic activity, ceftazidime is an improvement upon existing beta-lactam antibiotics in clinical use and can be regarded as a possible alternative to gentamicin.

Scand J Dent Res, 1981 Jun, 89(3), 235 - 8
Short-term investigation on the influence of cigarette smoking upon plaque accumulation; Bergstrom J; The influence of cigarette smoking on plaque accumulation was studied in young adult males who endeavoured to stop smoking . Plaque accumulation was evaluated photogrammetrically during a 5-d smoking period and, after an interval of at least 30 d, during a non-smoking period of the same length . It was found that the amount of plaque was comparatively larger and plaque accumulation rate consequently increased in smokers throughout the smoking period . The differences were small, however, and not statistically significant . The result substantiates the view that cigarette smoking has no antibacterial potency so as to reduce plaque formation on tooth surfaces.

Jpn J Antibiot, 1981 Jun, 34(6), 881 - 92
{A study on cefmetazole in the neonatal period (author's transl)}; Iwai N et al.; The authors studied the antibacterial activity, absorption and excretion, and clinical use of cefmetazole in neonatal period, and obtained the following results . 1 . The minimal inhibitory concentrations (MICs) of cefmetazole (CMZ) were measured, to compare with those of cefazolin (CEZ), for clinical isolates of S . aureus (31 strains), E . coli (29 strains) and K . pneumoniae (30 strains) . On a cumulative percentage basis, 77% of S . aureus, 76% of E . coli and 90% of K . pneumoniae were inhibited by less than or equal to 3.13 microgram/ml of CMZ with a higher inoculum size . When compared with CEZ, MICs of CMZ were found to be superior or equal against E . coli, K . pneumoniae and some of S . aureus, but to be inferior against most of S . aureus . Most of strains which were resistant to CEZ were most sensitive to CMZ . These results suggest that CMZ is highly active against Gram-negative bacteria and is stable to beta-lactamase . 2 . The serum concentration was measured in 7 neonates (5 approximately equal to 25 day-old) and 5 infants (1 approximately 3 month-old) after a single intravenous administration of 20 approximately 25 mg/kg of CMZ . The mean concentration in neonates was 68.3 microgram/ml at 1/2 hour postinjection, 57.0 microgram/ml at 1 hour, 35.4 microgram/ml at 2 hours, 18.1 microgram/ml at 2 hours, 18.1 microgram/ml at 4 hours and 9.5 microgram/ml at 6 hours . The mean half-life was 2.04 hours . The peak concentration of each neonate seemed to be related more to individual variation than to the days after birth . The mean concentration in infants was 60.7 microgram/ml at 1/2 hour, 42.8 microgram/ml at 1 hour, 22.2 microgram ml at 2 hours, 9.2 microgram/ml at 4 hours and 3.2 microgram/ml at 6 hours . The mean half-life was 1.31 hours . There was little difference in the mean peak concentration between neonates and infants, but the mean concentration after that were higher in neonates than infants . It was apparent that the half-life tends to be shortened in proportion to advanced age in days and months . 3 . CMZ was administered clinically in 3 cases of acute bronchopneumonia . Its clinical effect was excellent or good in all of the cases . No adverse reaction or abnormal laboratory values were found.

Lancet, 1981 May 30, 1(8231), 1192 - 3
The how of breast milk and infection; Control of bovine neonatal diarrhoea by management techniques; A four year study of bovine neonatal mortality on 34 dairy farms and an agricultural institute's calf unit showed that 280 (3.2 per cent) of 8752 calves died mainly from diarrhoea and, or , septicaemia . The relationship between management methods and mortality rates were studied at the calf unit . When infection rates were kept low by good standards of hygiene and an adequate quantity of colostrum was fed immediately post partum, morbidity and mortality rates were 8.3 per cent and 1.2 per cent respectively, compared with 36 per cent and 4.1 per cent when hygiene was poor and colostrum was withheld until six hours post partum . Ninety-five sick calves were given either glucose-glycine electrolyte solution orally (41 calves) or the electrolyte solution in combination with an antibacterial agent (54 calves) to compare the efficacy of these treatments . Recovery rates, duration of illness and live-weight gains showed no significant difference between the treatments . Mean serum immunoglobulin levels (zinc sulphate turbidity test) of calves at 30 hours old were poor indicators of the future health status of any individual calf . Results indicated that good management with emphasis on hygiene and early feeding of colostrum reduced losses due to neonatal diarrhoea and septicaemia from 4 per cent to 1.2 per cent.

Pharmazie, 1981 May, 36(5), 336 - 7
Studies in potential organo-fluorine antibacterial agents . Part 6: Synthesis and antibacterial activity of some new fluorine containing 1,3,4,5,7-pentasubstituted dipyrazolo{3,4-b,; 4,3-3}pyridines; Joshi KC et al.; Ten new fluorine containing dipyrazolo {3,4-b;4,3-3}pyridines have been synthesized as possible antibacterial agents . The synthesis involves the condensation of 5-amino-1,3-disubstituted pyrazoles with an appropriate arylaldehyde at 220-240 degrees C . The synthesized compounds have been characterized by their m . p.'s elemental analysis, TLC, IR, 1H-NMR and 19F-NMR . A representative number of compounds have also been screened for their antibacterial activity and most of them were found to inhibit the growth of different bacteria.

J Med Chem, 1981 May, 24(5), 639 - 43
Preparation and antibacterial activity of delta 1-thienamycin; Shih DH et al.; delta 1-Thienamycin (2), a double-bond isomer of thienamycin, was prepared by isomerizing N-{{(p-nitrobenzyl)oxy}-carbonyl}thienamycin p-nitrobenzyl ester (5b) with DBU in Me2SO followed by hydrogenolysis of the protecting groups . When evaluated in a disc-diffusion antibacterial assay, delta 1-thienamycin was found to be essentially devoid of activity . The lack of antibacterial activity was ascribed to a chemically less reactive beta-lactam amide bond than that found in thienamycin.

J Lab Clin Med, 1981 May, 97(5), 646 - 53
Presence of a serum hemagglutinin (lectinlike factor) in cystic fibrosis homozygotes and heterozygotes; Lieberman J et al.; A lectinlike activity was discovered in serum from 25 patients with CF, 70 obligate heterozygotes (parents), and 18 of 27 siblings (67%) of 675 controls, 4.2% were found to have a positive test for the CF-lectin, approximating the 5% estimated prevalence of CF heterozygotes . The CF-lectin can be detected by dextran-enhanced agglutination of mouse RBCs and confirmed by agglutination inhibition with D-fructose . This simple and inexpensive assay has been found useful to detect carriers of the CF gene, but variability of commercial dextran and some unusual characteristics of the lectin itself have interfered with the successful completion of blind studies . All sugar moieties present in mucus inhibit the agglutination of mouse RBCs by CF serum, implying that the CF-lectin can bind the glycoproteins of mucus . The factor may play a role in the pathogenesis of Cf by stimulating mucus secretion and reacting with mucous glycoproteins to cause their precipitation . Most antibiotics remove or inhibit the CF-lectin activity, suggesting a therapeutic effect of antibiotics unrelated to their antibacterial action . This discovery of a lectinlike factor in the blood of patients with CF and their parents opens a new area for investigation of this devastating disease.

J Bacteriol, 1981 May, 146(2), 656 - 9
Plasmid deoxyribonucleic acid and translucent-to-opaque variation in Mycobacterium intracellulare 103; Mizuguchi Y et al.; After treatment with mitomycin D and other antibacterial agents, a translucent, smooth-colony-forming mycobacterium, isolated from sputum and designated as Mycobacterium intracellulare strain 103, gave rise to variants forming opaque colonies . These opaque variants were more sensitive streptomycin, kanamycin, viomycin, and rifampin than were the wild-type translucent variants . Plasmid deoxyribonucleic acids taken from translucent strain cells and from cells of certain opaque variants were analyzed by agarose gel electrophoresis . Two plasmids of molecular weights of approximately 2 x 10(6) and 50 x 10(6), respectively, were found in the wild-type translucent cells; one of them, the 2 x 10(6)-molecular-weight plasmid, was always missing from deoxyribonucleic acids of the opaque variant cells . The results suggested that translucent colonial appearance and antibiotic resistance of the strain are plasmid-determined functions.

Drug Intell Clin Pharm, 1981 May, 15(5), 325 - 30
Trimethoprim: clinical use and pharmacokinetics; Friesen WT et al.; The recent marketing of trimethoprim (TMP) as a single drug has resulted in interest in the use of this drug to treat common infections . The history and antibacterial properties of TMP are reviewed . Indications for the clinical use of TMP are presented, and possible new uses for the drug are considered . The significance of adverse effects is discussed . The pharmacokinetic properties of TMP are reviewed with particular emphasis on the renal handling of the drug and its advantages over TMP/sulfonamide combinations in relation to renal function and toxicity.

J Dent Res, 1981 May, 60(5), 927 - 32
Effect of topically-applied solutions of iodine, sodium fluoride, or chlorhexidine on oral bacteria and caries in rats; Caufield PW et al.; Antibacterial levels of iodine, chlorhexidine or sodium fluoride were topically applied to the molar teeth of rats . The effect of these agents on buccal and sulcal caries, as well as on certain oral bacterial populations was assayed . All three agents exerted a significant cariostatic effect which was site specific . Buccal caries incidence and reductions appeared correlated to S . mutans counts, while sulcal caries was better correlated to total cultivable counts . These studies suggested that the simultaneous application of iodine and NaF might exert an additive cariostatic effect.

Antibiotiki, 1981 May, 26(5), 323 - 7
{New antibiotic, cinropeptin, from a culture of Act . cineraceus}; Frolova VI et al.; Cinropeptin, a new antibacterial antibiotic, was isolated from the mycelium of a culture classified as belonging to Act . cineraceus . Its empirical formula is C50H63N11O12S6, {alpha}D--169.4 degrees (C 0.36, CHCl3) . The UV absorption maxima of the antibiotic in an alcoholic solution were observed at 218, 232, 304 and 365 nm . The IR absorption bands were recorded at 3370, 1660, 1600, 1530, 1140 and 1100 cm-1 . Cystin, glycine and methylamine were detected in the acid hydrolysate of cinropeptin . Study on the products of the antibiotic partial oxidation with performic acid and comparison of the sulfur percentage and molecular weight showed that the molecule of cinropeptin contained 3 residues of cystin.

J Antibiot (Tokyo), 1981 Apr, 34(4), 403 - 11
4-N-(2-aminoethanesulfonyl)fortimicin B and 4-N-(p-aminobenzenesulfonyl)fortimicin B; Tadanier J et al.; Methods have been developed for preparation of 4-N-arenesulfonylfortimicins B and 4-N-alkanesulfonylfortimicins B from derivatives of fortimicin B-1,5-carbamate . 4-N-(2-Aminoethanesulfonyl)fortimicin B and 4-N-(p-aminobenzenesulfonyl)fortimicin B have been prepared and found to be devoid of antibacterial activity.

J Med Chem, 1981 Apr, 24(4), 454 - 7
Structure-activity relationships in dihydropteroate synthase inhibition by sulfanilamides . Comparison with the antibacterial activity; De Benedetti PG et al.; A set of 12 acidic, 5 imidic, and 5 amidic sulfanilamides (SA) were tested for their inhibitory activity on dihydropteroate synthase of Escherichia coli . The enzyme inhibition indexes (EII50) were compared with the growth inhibition indexes (GII50), and electronic structures of SA and cell permeability effects were discussed as possible determinant factors of the observed variation of the activity in the SA set . The results strongly support the following conclusion: (a) permeability factors are highly effective in depressing the activity of SA in growth inhibition with respect to enzyme inhibition, but they do not appear to contribute significantly to the activity variation; (b) the activities of the different SA, both in growth and enzyme inhibition experiments, are well accounted for by the electronic features of these compounds.

Acta Pathol Microbiol Scand {B}, 1981 Apr, 89(2), 129 - 31
Effects of antibacterial agents on the elimination of 32P-labelled Escherichia coli by human polymorphonuclear cells (PMN); Melby K et al.; Eight antibacterial agents, cephalothin, colistin, doxycycline, erythromycin, gentamicin, chloramphenicol, oxytetracycline and trimethoprim were studied in a phagocytic system using human polymorphonuclear cells (PMN) and a radio-labelled strain of Escherichia coli as test microbe . 100 micrograms/ml of either doxycycline or trimethoprim appeared to reduce the elimination of labelled products from the PMN . The effect of doxycycline was independent of heat-labile serum factors.

Lepr India, 1981 Apr, 53(2), 278 - 84
Clinical trial with CIBA 1906 in lepromatous leprosy; Anand LC et al.; Drug trial with CIBA 1906 was conducted in 50 cases of lepromatous leprosy who were intolerant to dapsone therapy . Drug was tolerated well and lepra reactions were infrequent and mild . Clinical improvement was seen in 72% cases whereas no appreciable change was detected in 28% cases . An average reduction of 0.4 in BI was detected in 62% cases, while remaining cases did not show any reduction in BI . No significant side effects were encountered during the study . Antibacterial activity of CIBA 1906 was not found superior to dapsone.

Ital J Orthop Traumatol, 1981 Apr, 7(1), 103 - 13
Investigation into the antibacterial activity in vitro of cement-antibiotic mixtures; Greco F et al.; An investigation was made into the antibacterial activity in vitro of CMW cement and antibiotic mixtures . The results of this study are reported and the risk factors are discussed . On the basis of our studies, the use of this mixture in clinical practice would appear to be premature.

Jpn J Antibiot, 1981 Apr, 34(4), 521 - 31
{Fundamental and clinical studies on cefotaxime in the field of obstetrics and gynecology (author's transl)}; Motomura R et al.; Fundamental and clinical studies were made on cefotaxime (CTX), a new cephalosporin antibiotic . The following results were obtained: 1 . Antibacterial activity: At a concentration of 3.13 mcg/ml, CTX inhibited the growth of 90.2% of 92 strains of Gram-negative rods and 80.0% of 15 strains of Gram-positive cocci . 2 . Concentrations of CTX in body fluids and genital organs after 2 g i.v.: (1) CTX level in pus reached the peak (5.6mcg/ml) at 2 hours after administration . (2) Mean CTX levels in the pelvic space exudate reached the peak (28.0 mcg/ml) at 2 hours after administration . (3) CTX levels in the uterine appendages and uterus reached the peak (8.9 and 4.5 mcg/g, respectively) at 100 to 280 minutes after administration . 3 . Clinical results: CTX was excellent in 7 of 13 cases and good in the remaining 6 cases . The response rate to CTX was 100% . 4 . The bacteriological effect: The bacteriological effect of CTX was also 100% . Bacteria were eradicated in 7 of the 10 cases where organisms were demonstrated before CTX treatment . Partial reduction bacteria was observed in the remaining 3 cases . 5 . No side effect attributable to CTX was observed.

J Fam Pract, 1981 Mar, 12(3), 461 - 7
Prophylactic antibiotics in surgery: a rationale for the family physician; Lennard ES et al.; Antibiotic administration can effectively reduce the risk of postoperative wound infection under specific circumstances . Maximal protection is obtained when an antibacterial concentration of a bacteriologically appropriate antibiotic regimen is circulating within target tissues at the time of bacterial contamination . This protection is obtained during a finite period, usually not exceeding four hours following bacterial seeding of tissues . The preservation of intact host defense mechanisms is of ultimate importance in preventing wound infection . When defenses are compromised or when an inoculum is of a size that can overwhelm host defenses, the perioperative administration of antibiotics can significantly reduce infection risk . However, antibiotic use must not lead to a relaxation of good surgical judgment and technique.

Jpn J Antibiot, 1981 Mar, 34(3), 367 - 73
{Clinical studies of cefoxitin in the pediatric field (author's transl)}; Kida K et al.; 1 . The in vitro antibacterial activity of cefoxitin was nearly equal to that of CEZ and CET against the 6 species of clinically isolated strains . Cefoxitin, furthermore, had an antibacterial activity against the strains of P . morganii resistant to CEZ and CET . 2 . Cefoxitin was applied to a total of 17 patients including 6 cases of bronchitis, 5 of pneumonia, 2 of enteritis, and 1 each of pharyngitis, laryngitis, sinusitis and lymphadenitis . The results showed an efficacy rate of 88% . In the 6 patients from whom the isolation of pathogenic organisms was possible, the bacteriological response to cefoxitin was appreciable the efficacy rate being 83% . Thus, it is considered that cefoxitin also has a significant antibacterial activity in vivo . 3 . As to the side effects following the administration of cefoxitin, urticaria-like eruption was observed in 1 case, and an elevation of transaminase in another . These findings, however, became normal soon after discontinuation of cefoxitin treatment.

Antibiotiki, 1981 Mar, 26(3), 140 - 2
{Microbial flora sensitivity to antibacterial agents in chronic pyelonephritis patients who have had acute kidney failure}; Shkrob OS et al.; The analysis of antibioticograms of patients with a history of chronic pyelonephritis and acute renal insufficiency is presented . It was found that the synergistic effect observed with the use of gentamicin in combination with carbenicillin or ampicillin with cephaloridin provides a decrease in the therapeutic doses of the drugs with a purpose of elimination of their side action.

Farmaco {Sci}, 1981 Mar, 36(3), 181 - 96
{Synthesis of 1-aroyl-4H(R)-thiosemicarbazides, the corresponding 5-aryl 4H(R)-1,2,4-triazolin-3-thiones and some derivatives of pharmaceutical interest}; Mazzone G et al.; A series of 1-aroyl-4H(R)-thiosemicarbazides (IV-XVIII) and the corresponding 5-phenyl-4H(R)-1,2,4-triazolin-3-thiones (XIX-XXXIII) were synthesized: biological assay demonstrated their in vitro antibacterial and antimycotic activities . The preparation of same hydrazinoaroylthiazoles (XXXIV-XXXVI) was reported also, obtained by condensation of 1-aroyl-4H-thiosemicarbazides with phenacyl bromide and the synthesis of thiazole{3,2-b}-s-triazol-3(2H)-ones (XLIX-LI) prepared by cyclodehydration of carboxymethylthiotriazoles (XLVI-XLVIII) . The results of pharmacological testing for both series of derivatives (XLIX-LI) and (XLVI-XLVIII) showed good antiinflammatory and antipyretic activities.

Am J Clin Pathol, 1981 Mar, 75(3), 304 - 11
Fusarium infection in burned patients; Wheeler MS et al.; The incidence of fungal infections of burn wounds is increasing because of the dramatic improvement in antibacterial chemotherapy and burn wound care . Species of Fusarium, common soil fungi and plant pathogens, are rarely isolated from burn wounds, and invasive disease due to these organisms is also rare . Therefore, a case of burn wound infection with dissemination due to F . oxysporum is reported; three other cases of burn wound colonization by Fusarium sp . are also reported . The literature on fungal infections of burn wounds is reviewed, and the importance of combined histologic and mycologic studies in the evaluation of such wounds is discussed.

J Nucl Med, 1981 Mar, 22(3), 274 - 8
Development of five-hour radiometric serum antibacterial assay for gram-positive cocci; Beckwith DG et al.; A preliminary report on a 5-hr radiometric serum antibacterial assay (ABA) for Gram-positive cocci is presented . The method agreed within +/- one twofold dilution with static ABA endpoints in 24/26 (92%) of the assays and with cidal ABA endpoints in 23/26 (88%) of the assays performed.

Minerva Med, 1981 Feb 28, 72(7), 435 - 42
{Broncaspin in the therapy of pediatric diseases of the respiratory tract}; Saldi M; A paediatric suspension of Broncaspin was administered to 32 children aged 2-12 yr hospitalised for acute respiratory infection of the respiratory apparatus or hyperpirexia with no evident location . The drug was given as the sole treatment in 9 cases, whereas combination with antibacterial drugs proved indispensable in the other 23 cases . The satisfactory results obtained, together with its excellent tolerability, show that the new preparation is active, and is capable of rapidly eliminating the symptoms, so that the general clinical picture is both evidently and persistently improved.

J Antibiot (Tokyo), 1981 Feb, 34(2), 193 - 201
6'-N-methylfortimicins A and B and 6',6'-di-N-methylfortimicins A and B; Tadanier J et al.; Selective 6'-N-alkylation of 1,2'-di-N-benzyloxycarbonylfortimicin B was effected by both catalytic and chemical reductive alkylation in the presence of aldehydes . These facile selective 6'-N-alkylations were used as the basis of the preparations of the 6',6'-di-N-methylfortimicins A and B, and the 6'-N-methylfortimicins A and B . Of these new 6'-N-methylated fortimicins, only 6'-N-methylfortimicin A has appreciable antibacterial activity, which was about half that of fortimicin A.

J Antibiot (Tokyo), 1981 Feb, 34(2), 160 - 70
Synthesis and structure-activity relationships of 7 beta-{2-(2-aminothiazol-4-yl)acetamido}cephalosporin derivatives . IV . Synthesis of 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid derivatives and related compounds; Ochiai M et al.; In an effort to improve the antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)acetamido}-cephalosporins by introducing a methoxyimino group into the 7-acyl side chain, geometrically isomeric 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acids and their derivatives were selectively synthesized . Structurally related acid derivatives were also synthesized . A facile and practical synthesis of an important starting material, 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetic acid, for the preparation of SCE-1365 which is now under extensive clinical trial was achieved.

Surgery, 1981 Feb, 89(2), 187 - 91
Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis . IV . The adjuvant effect of hemoglobin in granulocytopenic rats; Hau T et al.; Intraperitoneal inocula of pure Escherichia coli do not produce lethal peritonitis unless adjuvant materials are present . We have previously presented evidence that hemoglobin acts as an adjuvant in experimental Escherichia coli peritonitis by interfering with antibacterial neutrophil function . The hypothesis was further tested in normal Sprague-Dawley rats and rats depleted of granulocytes by pretreatment with busulfan and cyclophosphamide . Hemoglobin increased the lethality of Escherichia coli peritonitis in both neutropenic and normal rats . Furthermore, the early clearance of bacteria from the peritoneal cavity was equally depressed by hemoglobin in neutropenic and normal rats . We conclude that hemoglobin has some effect on intraperitoneal infections beyond its suppression of granulocyte function . This additional effect may represent interference with bacterial lymphatic absorption or peritoneal or systemic macrophage function or may be a manifestation of a nutritional effect of hemoglobin on bacterial growth.

Antimicrob Agents Chemother, 1981 Feb, 19(2), 326 - 7
Analysis of the in vitro interaction between vancomycin and cholestyramine; King CY et al.; Vancomycin and cholestyramine have been utilized both alone and in combination for the treatment of antibiotic-associated pseudomembranous colitis . Previous work for the treatment of antibiotic-associated pseudomembranous colitis . Previous work has demonstrated significant binding of vancomycin by the anion-exchange resin . The antibacterial activity of vancomycin was markedly reduced when the suspension was centrifuged and the supernatant was tested for antibacterial activity . This study confirmed these findings but demonstrated that there was no immediate loss of antibacterial activity of bound vancomycin . The degree of inactivation appeared to be dependent upon the duration of incubation of vancomycin and cholestyramine in the testing system.

Clin Sci (Lond), 1981 Feb, 60(2), 179 - 84
Human saliva and semen: evidence for proteins common to both which do not occur in serum; Eckersall PD et al.; 1 . Rabbit antiserum to human whole saliva cross-reacts with both human serum and semen . After absorption of the antiserum by affinity chromatography on a column of immobilized serum protein, the cross-reactions with serum were eliminated . 2 . The absorbed antiserum, however, still cross-reacted with semen thus indicating the presence of proteins with immunological similarity in both saliva and semen, but which did not occur in serum . 3 . Some of these proteins clearly showed a reaction of complete immunological identity between saliva and semen . 4 . The presence of the non-serum proteins in both saliva and semen might be related to common functions in both such as lubrication or antibacterial activity.

J Antibiot (Tokyo), 1981 Feb, 34(2), 171 - 85
Synthesis and structure-activity relationships of 7 beta-{2-(2-aminothiazol-4-yl)acetamido}cephalosporin derivatives . V . Synthesis and antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido}-cephalosporin derivates and related compounds; Ochiai M et al.; In order to improve the antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)acetamido}-cephalosporins new derivatives having a methoxyimino moiety in the 7-acyl side chain and related compounds were synthesized . Of these, 7 beta-{2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido}-cephalosporins were found to possess excellent activity against a variety of Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains . An extensive study of structure-activity relationships led to the selection of 7 beta-{2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido}-3-{(1-methyl-1H-tetrazol-5-yl) thiomethyl}-ceph-3-em-4-carboxylic acid, SCE-1365, for further biological and clinical evaluation.

Am J Vet Res, 1981 Feb, 42(2), 244 - 50
Effects of bovine viral diarrhea virus infection on bovine polymorphonuclear leukocyte function; Roth JA et al.; Four procedures were used to evaluate the function of polymorphonuclear leukocytes (PMN) isolated from the blood of cattle experimentally infected with bovine viral diarrhea (BVD) virus: (1) uptake of am emulsion of paraffin oil and Escherichia coli lipopolysaccharide, (2) nitroblue tetrazolium reduction, (3) chemiluminescence, and (4) iodination, or the conversion of iodide to a trichloroacetic acid-precipitable form . A marked impairment of iodination was consistently observed after infection with either a cytopathogenic or a noncytopathogenic strain of BVD virus . A corresponding decrease in paraffin oil uptake, nitroblue tetrazolium reduction, and chemiluminescence was not observed . Serum from BVD virus-infected animals did not depress iodination by normal control PMN in vitro . The iodination, procedure evaluates the activity of the myeloperoxidase, hydrogen peroxide, halide system . This system has potent bactericidal, fungicidal, and virucidal effects . The data indicate that oxidative metabolism by PMN from BVD virus-infected cattle is normal, but that the myeloperoxidase, hydrogen peroxide, halide antibacterial system is impaired . This could be explained by an inhibition of degranulation in PMN from infected cattle . The observed defect in iodination by PMN after BVD virus infection was compounded by a decrease in the number of circulating PMN . The impairment of PMN function may partially explain the increased susceptibility of cattle to secondary bacterial infection during infection with BVD virus.

Antimicrob Agents Chemother, 1981 Feb, 19(2), 234 - 7
Preferential inhibition of ribonucleic acid synthesis by a new thiosemicarbazone possessing antibacterial and antiparasitic properties; Brown RE et al.; We determined the influence of the azacycloheptane derivative (H) of a 2-acetylpyridine thiosemicarbazone on growth and macromolecular synthesis in Escherichia coli AT-9 . Thiosemicarbazone H caused bacteriostasis and a primary inhibition of ribonucleic acid synthesis; secondary effects included inhibition of deoxyribonucleic acid and protein synthesis . Addition of cooper or other transition elements was not necessary for these inhibitions.

Med J Aust, 1981 Jan 10, 1(1), 19 - 23
Inactivation of a rotavirus by disinfectants; Tan JA et al.; Rotavirus SA 11, clarified and in human faeces, was exposed to eight commonly used hospital and laboratory disinfectants for periods between 15 seconds and two hours . Of the three hard disinfectants tested, 0.95 by volume (95% v/v) ethanol and 0.05 by volume (5% v/v) Biogram were more effective in inactivating SA 11 than 4% (w/v) or 10% (w/v) formaldehyde, with 0.95 by volume ethanol being the most effective of all of the disinfectants tested . None of the skin disinfectants tested, Betadine, Hexol, Hibiclens and Hibitane in alcohol, were very effective against the rotavirus in the presence of faeces, although Hexol and Hibitane in alcohol inactivated clarified SA 11 fairly quickly . Because of its rapidity of action against SA 11, even in the presence of faeces, and relatively non-deleterious effect on the skin, 0.95 by volume ethanol may be more useful as a handwash than these skin preparations . Undiluted Milton Antibacterial Solution gave very variable results, while the same solution diluted 1 in 80 had little effect on clarified SA 11.

C R Seances Acad Sci III, 1981 Jan 5, 292(1), 37 - 40
{A new synthetic antibacterial : 1-ethyl-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxo-1, 4-dihydroquinolin-3-carboxylic acid (1589 R.B.)}; Goueffon Y et al.; The 1,4-dihydro-1-ethyl-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline- 3-carboxylic acid (1589 R.B.) is a broad antibacterial agent active in experimental infections . The toxicological and pharmacokinetic profiles of the compound administered as methane sulfonic salt (1589 m R.B.), seem to suggest the possibility of using it in systemic infections.

Chemotherapy, 1981, 27(2), 114 - 6
Presence of antibacterial agents in blood units collected from healthy voluntary donors; Michel J et al.; 10,991 sera collected from voluntary blood donors were tested during a 1-year period (1979) for the presence of antibacterial drugs . Antibacterial activity was found in 0.25% of them, and could be related to beta-lactam antibiotics and to cotrimoxazole . The implications of these findings are discussed.

Arch Immunol Ther Exp (Warsz), 1981, 29(6), 813 - 21
Synthesis and biological properties of 5-benzoylamino-3-methyl-4-isoxazolocarboxylic acid derivatives; Machon Z et al.; A series of amides of 5-amino-3-methyl-4-isoxazolocarboxylic acid derivatives was synthesized and tested for antiinflammatory and antibacterial activity . P-etoxyphenylamid and p-chlorophenylamid of 5-benzoylamino-3-methyl-4-isoxazolocarboxylic acid displayed strong antiinflammatory and antibacterial effect . The most potent effect of these amides is accounted for the presence of benzoyl group in position 5 of isoxazole group.

Vet Med Nauki, 1981, 18(7), 105 - 10
{Use of the leaves of the dandelion (Taraxacum officinale L.) in the feeding of the silkworm Bombyx mori L.}; Manchev M; Experiments were carried out with eggs of Bombyx mori of the J--124xC--122 hybrid, imported from Japan . Tested was the feeding of the silkworm moth on leaves of dandelion (Taraxacum officinale L.) up to the end of the III instar . Feeding was also carried out with dandelion leaves up to the end of the IV instar, which, immediately prior to offering to the moths were sprinkled with water solutions of flurazolidon, 1.5 per cent, chloramphenicol with propylen glycol (5%)--50 cm3 each/1 of water or nalidixic acid, 2.5 per cent . The effect was studied of the antibacterial preparations applied to every kind of feed on the amount of microflora in the alimentary tract . It was found that moths given dandelion leaves reached the III instar, however, there was a very early manifestation of spontaneous nuclear polyhedrosis and bacterial infections of the alimentary tract . The addition of antibacterial preparations reduced the outbreaks of the two diseases and the microflora in silkmoths . Discussed is the possibility of the wide use of broad-spectrum antibacterial drugs in the prevention of these diseases.

Ann Rech Vet, 1981, 12(2), 129 - 32
{Choice of antiseptics for use in footbaths for cattle (author's transl)}; Grongnet JF et al.; Eight antiseptics to be used in footbaths for cattle, were compared : formol, cuprum sulphate, formol associated with cuprum sulphate, Javel water, Cresyl and some other products more recently introduced into practice . For each one, evolution of antibacterial activity connected with utilization on animals, moistening power and possible injury caused were observed . The best results have been obtained with formol, formol associated with cuprum sulphate and Cresyl which have exhibited persistent high level antibacterial activity without related injury in spite of numerous applications . On the other hand, weak organic matter resistance which seems to characterize Javel water, synthetic phenols, amphoteric amino acids and iodophores makes them unsuitable for use in footbaths.

Arch Orthop Trauma Surg, 1981, 99(2), 105 - 8
Concentration of antibacterial agents in rat bone . A comparative study of gentamicin, ampicillin and cephaloridine; Papadopulos JS et al.; The concentrations of Gentamicin, Ampicillin and Cephaloridine in thigh rat bone were studied . Measurements were done after a 24 h administration for 3 different times . Measurable quantities in the bone for the three antibiotics were detected . The best levels in relation with the M.I.C . of 4 microorganisms occurred in Cephaloridine (and in measurements of serum and bone (microgram/g) . The concentration in the serum does not represent concentration in the bone . The most convenient parity was for Cephaloridine . The elimination of the drug in the bone was impressive after 2h . The slower fall occurred in Cephaloridine . Ampicillin had the same level in 4 and 6h . Gentamicin and Cephaloridine had failed to present measurable quantities in some of the animals of the last measurement.

G Batteriol Virol Immunol, 1981 Jan-Jun, 74(1-6), 77 - 100
{Antibacterial activity in vitro of several aminoglycosides and cephalosporins}; Piantieri G et al.; The "in vitro" rate of killing on different microorganisms was studied for three cephalosporins (cephazolin, cefuroxime and cefoxitin) and four aminoglycosides (gentamicin, tobramycin, sisomicin and amikacin) . In all experiments an inoculum effect and a negative influence by adding plasma to the nutrient broth were observed, the latter phenomenon being more pronounced with cephalosporins than with aminoglycosides . While the "in vitro" effects of antibiotic concentrations equal to the MIC or to the MBC were informing on the intrinsic antibacterial activity of single drugs, a more satisfactory approach to therapeutic reality was provided by studying the "in vitro" effects of concentrations equal to peak blood level or to the logarythmic mean of blood level, that is a parameter which contributes to the blood-tissue diffusion gradient . Our data show that antibiotics provided with an higher peak blood level and a more sustained logarythmic mean of blood concentrations, and an higher ratio between these two kinetics parameters and MIC or MBC, are favoured in the experimental system here adopted.

Anesth Analg (Paris), 1981, 38(7-8), 341 - 5
{The infusion of packed red cells . Usual difficulties (author's transl)}; Otteni JC et al.; This infusion used instead of whole blood has become increasingly common . However in our, as in other french institutions, the volume and the hematocrit of blood contained in each unit varies often notably . In addition, because of their high viscosity packed erythrocytes cannot be transfused rapidly enough . For transfusion in emergency situations and transfusion in operating room, following suggestions could be made to blood banks: --each unit should provide information on its content (volume and hematocrit or hemoglobin content); --units with low blood content should be transfused outside the operating room, whereas units containing high volumes should be reserved for peroperative transfusion in order to reduce charge of manipulation; --packed erythrocytes units should be prepared in order to allow same transfusion rates as whole blood (i.e . an average of 100 ml per minute for one transfusion line); --packed erythrocytes units should contain about 80 ml of plasma for an average total concentrate volume of 260 ml in order to provide enough antibacterial defense components; --units of fresh whole blood should be provided when approximately 150 p . cent of recipient's blood volume has been replaced in order to maintain the critical platelet level.

Hepatology, 1981 Jan-Feb, 1(1), 21 - 7
Protection by antibiotics against experimental focal cholangitis produced in mice by a schistosomicidal isothiocyanate; Batzinger RP et al.; Oral administration to mice of high doses of 4-isothiocyano-4'nitrodiphenylamine (amoscanate), a potent antischistosomal drug, produced focal necrotizing lesions of the large intrahepatic and extrahepatic bile ducts and the gallbladder . Coadministration of erythromycin and, to a somewhat lesser degree, of paromomycin, markedly reduced the effects of amoscanate on the biliary tract . These results suggest that amoscanate may be converted to a cholangiotoxic product by one or several constituents of the enteric bacterial flora . Since erythromycin does not affect the antischistosomal activity of amoscanate, coadministration of an antibacterial agent can reduce toxic effects of a drug while full chemotherapeutic activity is maintained . The possibility of toxic effects of metabolites of xenobiotics produced by intestinal bacteria deserves attention and the experimental production of focal intrahepatic and extrahepatic cholangitis by such drug metabolites suggests a possible mechanism in human bile diseases.

Zentralbl Chir, 1981, 106(11), 724 - 33
{Mesenteric cysts (author's transl)}; Pfeiffer M et al.; Mesenteric cysts belong to the rare abdominal diseases . Histomorphologically, they are classified as cystic lymphangiomas . Even though most frequently localized in the mesentery of the small intestine, they can originate from any part of the abdominal cavity with two peritoneal linings . The content of the cysts is either serous or chylous possessing immunologic active proteins . This is demonstrated by its highly antibacterial activity . Whereas in children the onset of symptoms is acute due to intestinal obstruction, in adults it is mainly chronic abdominal pains without exact localisation and often in combination with a longstanding palpable tumour . In addition to routine procedure the diagnostics includes sonography, cavography and barium meal radiography of the stomach and intestines . In some cases, especially those with solid parts angiography and computer-tomography are of additional value . Surgery is the therapeutic method of choice . Preference is given to enucleation and resection with or without removal of part of the intestine corresponding to the mesentery baring the cyst . Drainage methods are of historical interest only . In our 9 cases (3 children and 6 adults) resection was performed in 7 and enucleation in 2 cases . The postoperative courses were uneventful.

Pharmatherapeutica, 1981, 2(9), 559 - 64
The efficacy of twice daily cephalexin; Browning AK; A multi-centre study in general practice was carried out to compare the efficacy of two doses of cephalexin-500 mg or 1 g - given in a twice daily dosage regimen to 752 patients with respiratory or soft tissue infections . After 5-days' treatment, over 80% of the patients were cured or considerably improved, with no differences between the two treatment groups . Considering the lower respiratory and soft tissue infections together, 1 g cephalexin twice daily produced a better clinical response after 48-hours' treatment, suggesting a more rapid response with the higher dosage, but this trend did not reach statistical significance . Twice daily cephalexin therapy was also effective in patients with concurrent illness, and in those patients who had been treated unsuccessfully with other antibacterial therapy in the week prior to trial entry . No drug interactions were reported and the incidence of side-effects was low.

Clin Ther, 1981, 3(6), 425 - 35
Disposition of cefoxitin in patients with pleural effusion; Barrueco M et al.; The pharmacokinetics of cefoxitin were studied in nine patients with pleural effusion of varied etiologies . All patients received a single intravenous bolus of 30 mg/kg . Cefoxitin levels were determined simultaneously in plasma and pleural fluid by means of a microbiologic plate diffusion method . The antibiotic follows a two-compartment open kinetic model . In the pleural fluid, maximum concentrations of cefoxitin of 19.72 +/- 9.72 microgram/ml were reached two hours after administration . The fraction of the antibiotic that reaches the pleural fluid represents 0.22% to 4.03% of the dose administered . The disappearance constant of the antibiotic from the pleural fluid is significantly smaller (Kd = 0.15 +/- 0.03 hours-1) than the elimination constant determined from the plasma levels (K13 = 2.27 +/- 0.90 hours-1) . Cefoxitin was always found in antibacterial concentration in the pleural fluid for a considerable period of time.

J Antibiot (Tokyo), 1981 Jan, 34(1), 5 - 12
Aminoglycosides . V . Synthesis of glucopyranoside derivatives of neamine modified in the 2-deoxystreptamine ring; Pfeiffer FR et al.; trans-4-Aminocyclohexanol-2'-amino-alpha-D-glucopyranosides were prepared which are derivatives of neamine having the 3-amino and 5 and 6 hydroxyl groups of the 2-deoxystreptamine ring replaced with hydrogen . The 2'-amino-alpha-glycosides were synthesized by the method of LEMIEUX using a chloro nitroso dimer of a glucal and appropriately substituted cyclohexanols . Reductive deblocking of the intermediate 2-oximino derivatives afforded paromamine and neamine analogues . Two examples of 2'-amino-alpha-glycosides with ring-opened variations of the 2-deoxystreptamine aglycone are described . None of the compounds exhibited better in vitro antibacterial activity than neamine when compared against Gram-positive and Gram-negative bacteria.

J Antibiot (Tokyo), 1981 Jan, 34(1), 40 - 6
beta-lactam antibiotics derived from nitrogen heterocyclic acetic acids . 2 . Cephalosporin derivatives; Bambury RE et al.; Three cephalosporin derivatives were prepared from 1,4-dihydro-4-oxypyridine-1-acetic acid . These were the 7-aminocephalosporanic acid (7-ACA) derivative and the compounds with 5-methyl-1,3,4-thiadiazol-2-thiol and 1-methyl-1,2,3,4-tetrazole-5-thiol at C-3 of the cephalosporin nucleus . The antibacterial activity of the 7-ACA derivative was comparable to cephalothin, and that of the other two derivatives was comparable to cefazolin . The 7-ACA derivative, compared to cephalothin, was significantly less metabolized, was less protein bound, and had a longer half life.

Jpn J Antibiot, 1981 Jan, 34(1), 51 - 60
Studies on synergisidin; Jinnouchi H et al.; Penicillium sp . No . Y-11930 was isolated from soil sample collected at Shimouma, Setagaya, Tokyo in September 1978 . Synergisidin produced by the strain was obtained with high yield in starch-corn steep liquor medium, extracted with ethyl acetate at pH 5.0 and crystallized from ethyl acetate after decolorization with active charcoal . The antibacterial activities of synergisidin against Gram-positive and Gram-negative bacteria and Mycobacterium were almost nothing but synergisidin showed weak activities against eumycetes with MICs of 6.25-100 microgram/ml . However, synergidisin was confirmed and discovered to show 30-125-fold strong synergistic effects against Candida sp . in particular with addition to extremely small quantities of imidazole antimycotics such as econazole, miconazole and clotrimazole . The acute toxicity was LD50 smaller than or equal to 250 mg/kg in mice (i.p.) . the morphological degenerative effect on HeLA cells was observed in concentrations of more than 0.122 microgram/ml . The chemical structure of synergisidin was estimated as 7, 16-dihydroxy-2-methyl-4-oxo-3-oxabicyclo {10 . 3 . 1} hexadeca-5, 10-diene or 2, 15-dihydroxy-7-methyl-5-oxo-6-oxabicyclo (11 . 3 . 0} hexadeca-3, 11-diene (the same structure as decumbin, brefeldin A and ascotoxin) from various physiochemical properties but later, comparison with brefeldin A and ascotoxin revealed that synergisidin was identical with those.

Langenbecks Arch Chir, 1981, 353(4), 241 - 50
{Therapy of purulent peritonitis . Documentation of 78 cases and experience with taurolin (author's transl)}; Linder MM et al.; From three different surgical departments 78 patients with purulent peritonitis are analyzed according to cause, origin, and extent of peritonitis . Operative therapy is presented . As additional antibacterial therapy the new chemotherapeutic agent, Taurolin, with antiendotoxin-effect is used . The postoperative course (temperature exceeding 38 degrees C, secondary wound healing, day of discharge, and serious complications) is correlated with pre- and intraoperative parameters; for instance, 1 . postoperative fever occurs in one half of the patients, more frequently following perforation of stomach and duodenum; 2 . every second patient shows secondary wound healing, this happens even more often in peritonitis arising from biliary disease or appendicitis; 3 . in 29.5% of the patients serious complications arise, especially in patients with peritonitis originating in stomach, small intestine or large bowel; 4 . overall mortality of 11.5% is surpassed in patients with peritonitis originating from small intestine or large bowel . The so-called peritonitis-index (calculated on the basis of pre- and intraoperative factors) shows a significant difference between survivors and patients dying during the postoperative course . In 80% of the 78 patients with purulent peritonitis taurolin was effective as a substitute for the usual antibiotics.

J Pharm Sci, 1981 Jan, 70(1), 84 - 6
Synthesis and antibacterial and anticancer evaluations of alpha-methylene-gamma-butyrolactones; Heindel ND et al.; Nine new alpha-methylene-gamma-butyrolactones were synthesized by the Reformatsky condensation of ethyl alpha-bromomethylacrylate with ketones, aldehydes, and an epoxide . A unique spirobutyrolactone class was prepared by reaction of the zinc alkyl derivative and N-methylisatins . The compounds were evaluated against L-1210 and P-388 leukemia and the 9KB carcinoma of the nasopharynx . They also were screened in a microbiocidal and an antifungal assay . The spiro methylene lactone of 5-iodo-N-methylisatin displayed activity in the P-388, 9KB, and antifungal screens.

Arzneimittelforschung, 1981, 31(12), 2133 - 7
Fenticonazole, a new imidazole derivative with antibacterial and antifungal activity . In vitro study; Veronese M et al.; The activity of alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) compared with those of reference drugs, was tested in vitro on various bacteria and fungi . This compound showed in vitro an excellent activity against gram-positive microorganisms . The antifungal activity spectrum is very broad: dermatophytes, yeasts and dimorphic fungi were the most susceptible organisms . Fenticonazole showed in vitro at pH range 4-5 the highest activity against yeasts . The addition of inactivated bovine serum to the culture medium led to a slight decrease in activity of all the tested substances.

Ann Rech Vet, 1981, 12(1), 41 - 6
Antibiotic sensitivity testing: correlations between in vitro tests in vivo situations; Devriese LA et al.; This review discusses the correlations between in vitro antibiotic sensitivity test results and in vivo clinical situations . It is concluded that the relations between blood levels and minimal inhibitory concentrations of antibacterial drugs cannot always be applied as criteria of sensitivity . Important exceptions are local treatments and treatment of infections in body sites where antibiotics are concentrated . Examples of agreement and lack of agreement between in vitro test results and treatment results in infections caused by bacteria with acquired resistance are given . Finally, the special problem of the interpretation of results obtained in tests with intestinal bacteria and antibacterials used for growth promotion is discussed.

Probl Endokrinol (Mosk), 1981, 27(6), 79 - 83
{Changes in integral indicators of natural immunity in experimental hypo- and hyperthyroidism}; Moskvina TS et al.; Two natural immunity integral indices-the skin bactericidal action and the blood antibacterial activity-were studied in experimental rat hypo- and hyperthyrosis by means of original radioimmunoassay . A decrease in the skin bactericidal action was seen hypothyrosis, but as whole, this test proved to be insufficiently sensitive . An alteration of the blood antibacterial activity in hypo- and hyperthyrosis is characterized by an initial increase in this activity, followed by its lowering . The prolonged phase of the blood antibacterial activity growth was found in hyperthyrosis, whereas in hypothyrosis the decreased phase of the above activity was seen . The pronounced changes in the natural immunity level precede clinical manifestations of the thyroid affection . Radioimmunoassay is recommended for studying the blood antibacterial activity as a sensitive and informative test, allowing one to judge of the antibacterial immunity state.

Scand J Infect Dis, 1981, 13(4), 291 - 6
The relative potency of amoxycillin and ampicillin in vitro and in vivo; Mattie H et al.; The relative antibacterial efficacy of amoxycillin ampicillin was compared in vitro and in vivo against a strain of Escherichia coli in short-term experiments (hours) . The quadratic fit to the growth curves in vitro in the presence of the antibiotic gave concentration dependent parameters . The concentration effect curves for both antibiotics showed that amoxycillin varied between equipotent (at 2 mg/l) and twice as potent (at higher concentrations) as ampicillin . The relative efficacy in vivo was determined in a thigh muscle infection in irradiated as well as normal mice . Numbers of colony forming units 3 h after infection were dose (or concentration) dependent, the slopes for amoxycillin and ampicillin being parallel . Slopes in irradiated and non-irradiated mice differed significantly . In both kinds of animals the average potency ratio was 1.5 in favour of amoxycillin . Thus, no difference was found between the in vitro and in vivo situation regarding relative efficacy.

Nucleic Acids Symp Ser, 1981, (10), 55 - 8
Oxanosine, a novel nucleoside from actinomycetes; Yagisawa N et al.; Oxanosine, a novel nucleoside, has been isolated from the culture filtrate of a strain of Streptomyces . The structure was determined to be 5-amino-3-beta-D-ribofuranosyl-3H-imidazo {4,5-d} {1,3}oxazin-7-one by X-ray crystallographic analysis and chemical studies . Oxanosine showed weak antibacterial activity on peptone agar; for example, Escherichia coli K-12 (MIC 12.5 mcg/ml) . The antibacterial activity was antagonized by addition of guanine, guanosine and 5'-guanylic acid . Oxanosine inhibited the growth of HeLa cells in vitro (IC50 32 mcg/ml) and suppressed the growth of L-1210 leukemia in mice . The primary action of oxanosine appears to be inhibition of GMP-synthetase . Intravenous injection of 4 mg of oxanosine to mice does not show any toxic sign.

Curr Eye Res, 1981, 1(5), 259 - 66
Tobramycin in external eye disease: a double-masked study vs . gentamicin; Leibowitz HM et al.; A double-masked randomized study was conducted at four centers to compare the efficacy and safety of tobramycin and gentamicin ophthalmic ointment in the treatment of superficial external eye disease . Seventy-seven patients with blepharitis and/or conjunctivitis were evaluated for safety, and 56 of the 77 individuals also qualified for evaluation of drug efficacy . After a 10 day treatment regimen, 97% of the tobramycin treated patients and 91.3% of the gentamicin treated patients were clinically cured or improved . Antibacterial effectiveness studies in the conjunctiva showed that tobramycin eradicated or controlled 87.8% of the bacterial infections vs . 77.4% for gentamicin . There was also a 9.3% adverse reaction rate with tobramycin vs . 17.6% with gentamicin . Primary symptoms consisted of erythema, injection, discomfort and itching . All adverse reactions were mild and cleared upon discontinuation of the study drug . While the trends seem to favor tobramycin, no difference was statistically significant at the p less than or equal to 0.05 level . These results indicate that tobramycin is a clinically effective and safe topical antibiotic and that it is comparable to gentamicin for topical treatment of bacterial external eye infections . It also may be better tolerated than gentamicin.

Immun Infekt, 1981, 9(3), 113 - 8
{Influence of beta-lactamases on bacterial resistance (author's transl)}; Cullmann W; Several factors influence the antibacterial activity of beta-lactam antibiotics . Protection against attack by beta-lactam antibiotics can be provided by several mechanisms, e.g . the production of inactivating enzymes such as beta-lactamases . Gram-positive bacteria produce a penicillin-hydrolysing enzyme exhibiting only minor molecular variants; among gram-negative bacteria, however, there is a number of enzymes with various substrate profiles . Plasmid-mediated, species independent enzymes deserve special attention . The production of a beta-lactamase cannot be regarded as the sole determinant in resistance against beta-lactam antibiotics; moreover, it is the interaction with other mechanisms that provides protection against the attack of beta-lactam compounds . Above all, the ability of the antibiotic to penetrate the "outer membrane" at a sufficient rate to reach its target before being inactivated by beta-lactamases is especially important.

Scand J Infect Dis Suppl, 1981, 26, 130 - 4
Tinidazole in the treatment of infections of the upper respiratory tract; Lundberg C et al.; Sixteen patients with primary or secondary anaerobic infections of the maxillary sinus, mouth and throat were treated with tinidazole . The peak plasma concentration in eight patients given 2 g tinidazole initially followed by 1 g daily on the 5 subsequent days varied between 15 and 48 microgram/ml the first day and were only slightly lower during the following days . The mixed saliva/plasma concentration ratios ranged between 0.2 and 1.8 with a mean value of 0.85 . In eight patients with anginose infectious mononucleosis, a rapid improvement was observed after the onset of treatment . Normal body temperature and well-being was restored within 3 to 5 days . No bacteria considered to be involved in the infection of the throat were isolated from these patients, and it, therefore, seems unlikely that the clinical benefit is attributable only to antibacterial activity of tinidazole . Anaerobic infections in five patients with purulent maxillary sinusitis, two patients with acute exacerbation of atrophic pharyngitis and one patient with a necrotic ulcer of the tongue, were treated successfully with tinidazole.

Albrecht Von Graefes Arch Klin Exp Ophthalmol, 1981, 215(3), 187 - 91
{Antibacterial in vitro activity of sulfurhexafluoride (SF6) (author's transl)}; Clajus P et al.; The sterility of the gas sulfurhexafluoride (SF6) was proved by means of microbiological examinations . It was also shown that sulfurhexafluoride has no antibacterial influence on important clinically relevant bacteria.

Folia Microbiol (Praha), 1981, 26(2), 124 - 8
Antibiotic production by submerged culture of Melanconis flavovirens (Otth) Wehm; Sasek V et al.; The pyrenomycete Melanconis flavovirens under submerged cultivation produced antibiotics active against both bacteria and fungi . Glucose and corn-steep liquor were the best C and N sources for the antibiotic production, respectively . Supplementation with Tween-80 and enthylene glycol stimulated both antifungal and antibacterial antibiotic production, whereas oleic acid only the antifungal one . Addition of K2HPO4 also showed a positive effect . The optimal conditions for fermentation of the antifungal component are given.

Antimicrob Agents Chemother, 1981 Jan, 19(1), 134 - 8
Comparison of antibacterial and antiimmune effects of certain rifamycins; Kasik JE et al.; Comparison of the in vivo and in vitro immunosuppressive activities of the five rifamycins with their in vitro antibacterial and anti-ribonucleic acid polymerase activities indicated that correlation was poor . Examination of their activities on mitogen-induced blastogenesis in human peripheral blood leukocytes and inhibition of delayed-type hypersensitivity to partially purified protein derivative in immunized mice demonstrated that correlation was usually good . Antibacterial activity in cultures and the activities of the rifamycins inhibiting deoxyribonucleic acid-dependent ribonucleic acid polymerase appeared to correlate well . However, when these two types of activity, antiimmune and antibacterial, were compared, correlation was poor on occasion and indicated that the antiimmune activities and antibacterial activities of the rifamycins are probably not related.

Arzneimittelforschung, 1981, 31(8), 1290 - 5
Comparative in vitro activity and beta-lactamase stability of moxalactam and other selected cephalosporin antibiotics; Vuye A; (6R, 7R)-7-{{Carboxy(4-hydroxyphenyl)-acetyl}amino}-7-methoxy-3{{(1-methyl-1H-tetrazol-5-yl)thio}methyl}-8-oxo-5-oxa-1-azabicyclo{4,2,0}oct-2-ene-2-carboxylic acid (moxalactam, LY 127 935), a novel 1-oxa-beta-lactam, was proved to display similar antibacterial activity as cefotaxime against a number of beta-lactamase-producing gram-negative strains . The outstanding activity proved to be bactericidal in most cases and was only slightly influenced by variation of the inoculum size . The activity of cefotaxime and especially cefamandole on the contrary had rather a high inoculum-dependence . Moxalactam had equal stability to gram-negative beta-lactamases as has cefoxitin . Like cefotaxime and cefoxitin, the compound proved to be a potent inhibitor of cephalosporinases but not of broad spectrum beta-lactamases.

Eur Urol, 1981, 7(6), 359 - 62
Heparin - an examination of its antibacterial adsorption properties; Hanno PM et al.; One of the primary antibacterial defense mechanisms of the bladder is the action of the luminal mucopolysaccharide layer against adsorption of inoculated bacteria . Previous studies have shown that local instillation of the mucopolysaccharide heparin can prevent bacterial adsorption on the bladder mucosa denuded of this "antiadherence factor" . To determine whether this action was due to the mucopolysaccharide composition of heparin, or rather to its anticoagulant property, protamine sulfate (a basic protein with anticoagulant properties) was tested for antiadsorptive efficacy . Protamine offered no protection against bacterial adherence in the rabbit model . It appears that heparin's protective effect is unrelated to its action as an anticoagulant.

Drugs, 1981, 22 Suppl 1, 100 - 7
Clinical experience with cefoperazone in biliary tract infections; Mashimo K; The biliary excretion of cefoperazone in experimental animals, and humans, was investigated . Biliary excretion of cefoperazone in rats, rabbits, dogs, and monkeys was always higher than that of cephazolin . Biliary excretion was markedly reduced in experimentally-produced liver cirrhosis in rats . Comparing the biliary excretion of cefoperazone and cephazolin in a crossover study in patients, the excretion of cefoperazone was shown to be much higher than that of cephazolin . In clinical studies in 116 patients with biliary tract infections such as cholecystitis, cholangitis, and liver abscess, cefoperazone was effective in 90 (78%) . The incidence of side effects was low . In conclusion, cefoperazone was considered to be effective in treating biliary tract infections because of its broad antibacterial spectrum and high penetration into bile.

J Antibiot (Tokyo), 1981 Jan, 34(1), 22 - 7
Modification of spectinomycin . 2 . Derivatives of 4-dihydro-4-deoxy-4(R)-aminospectinomycin; Woitun E et al.; Acyl derivatives 5a approximately j and alkyl derivatives 7a approximately r of 4-dihydro-4-deoxy-4(R)-aminospectinomycin (1a) were prepared and tested for antibacterial activity . Only acyl compounds derived from long chain aliphatic acids showed activity in vitro, but were inactive when tested in vivo . All alkyl derivatives were active in vitro . In vivo however only the short chain derivatives 7a approximately c were active . Compound 7b showed higher activity than spectinomycin.

J Med Chem, 1981 Jan, 24(1), 88 - 93
1-Oxacephalosporins: enhancement of beta-lactam reactivity and antibacterial activity; Murakami K et al.; The effect of replacement of sulfur in the cephem nucleus by oxygen upon the beta-lactamase stability, infrared carbonyl frequency of the beta-lactam ring, and antibacterial activity was investigated . The replacement reduced the stability of beta-lactam compounds to beta-lactamases, increased the IR frequencies, and enhanced the intrinsic antibacterial activity against bacterial strains without beta-lactamase . The instability of 1-oxacephalosporins to beta-lactamases, in other words, high reactivity to the enzymes, seemed to be due to the enhanced chemical reactivity of their beta-lactam rings which was indicated by their higher IR beta-lactam carbonyl frequencies . Based on a view that acylation of the enzyme by beta-lactam compounds occurred in both cases of beta-lactamase hydrolysis and target enzyme inhibition, the suggestion was made that one of the factors which conferred the higher intrinsic antibacterial activity on 1-oxacephalosporins was their high reactivity to the target enzyme(s), as was the case with beta-lactamases.

Infect Immun, 1981 Jan, 31(1), 11 - 6
Mechanism of the bactericidal action of myeloperoxidase: increased permeability of the Escherichia coli cell envelope; Sips HJ et al.; The killing of Escherichia coli by isolated human myeloperoxidase plus hydrogen peroxide plus chloride ions was shown to proceed via an increased permeability of the bacterial cell wall . A correlation between the extent of the increased permeability and the number of surviving colony-forming units was found (P less than 0.0005) . The same phenomenon was observed with isolated human neutrophils . The permeability increase was shown to be limited, because low-molecular-weight substrate became freely permeant, but the bacteria retained their permeability barrier for protein . Furthermore, disruption of the permeability barrier was followed by destruction of cytoplasmic protein . The active antibacterial agent was probably hypochlorous acid, the direct product of the system, rather than singlet oxygen, the nonenzymic product of hypochlorous acid and hydrogen peroxide . This is concluded from the fact that the myeloperoxidase system could be mimicked by hypochlorous acid, whereas conditions that favor formation of singlet oxygen did not enhance this effect . The relevance of the system for killing of bacteria at neutral pH is discussed.

Carcinogenesis, 1981, 2(6), 489 - 94
Induction of endogenous viral gene expression by halogenated hydrocarbons; Pearson MN et al.; Endogenous avian RNA tumor virus gene expression was induced in chick embryo cells by the 1,1,1-trichloro-2-, 2-bis(p-chlorophenyl ethane) metabolites bis(chlorophenyl)acetic acid and dichlorodiphenyl dichloroethylene and the antibacterial agent hexachlorophene . Line 100 x 7, C/ABE, chick cell cultures were incubated with each of these chemicals or the known endogenous virus inducer bromodeoxyuridine . At subtoxic levels, all four chemicals induced the production of virus particles as determined by assay for the viral-specific reverse transcriptase and infectivity . Since the endogenous virus produced is of subgroup E and consequently unable to infect surrounding cells of the type C/ABE, amplification of the induced virions was accomplished by infecting the subgroup E susceptible cell line 15B C/C with supernatants from the chemically treated cultures . Fluorescent antibody treatment of line 100 x 7 C/ABE cultures showed approximately 35% to 40% of the cells stained in the chemically treated cell cultures, suggesting that only a portion of the cells were responding to the chemical induction.

Ann Anesthesiol Fr, 1981, 22(2), 207 - 11
{Serial measurement of serum levels of amikacin . Value in therapy}; Granthil C et al.; Amikacin serum levels were measured 256 times in 65 patients admitted into the intensive care unit for various reasons over 18 months . These measurements confirmed the dosage of 5 micrograms per kg repeated every 8 hours in patients with normal renal function . Forty eight hours before the first measurement, a control assay is essential to check that there is no residual antibiotic and that the antibacterial activity of the serum is zero . After this a single weekly control is sufficient to check that the residual level is effective and non toxic, i.e . between 2 and 6 micrograms per ml . However, in patients with acute renal insufficiency, there are three dosage schemas which should be used depending on the creatinine level . These three schemas are nevertheless not sufficient to continue effective therapy without a risk of toxic side effects . It is therefore necessary to check both the pack levels and the residual levels regularly from the beginning of treatment . Two to three weekly controls are essential to avoid a risk of toxic side effects.

Br Med J, 1980 Dec 13, 281(6255), 1597 - 600
Prophylaxis of infection after appendicectomy: a survey of current surgical practice; Campbell WB; Two hundred and eighty questionnaires were sent to junior surgical staff throughout England inquiring about their use of systemic antibiotic prophylaxis, topical antibacterial agents, and surgical drainage in appendicectomy . One hundred and seventy-five (63%) replies were received from 81 of the 87 hospitals included in the survey . Prophylactic systemic antibiotics were used by 78 surgeons (46%) when operating on a normal appendix but by 168 (99%) when the organ had perforated . Most surgeons started antibiotics before operation, but proportionately fewer did so when the appendix was gangrenous or perforated . Patients with severe contamination tended to receive longer courses of antibiotics, although the duration of administration varied considerably . Metronidazole was included in over 95% of all the prophylactic regimens and was often combined with other drugs when the appendix was gangrenous and perforated . Topical antibacterial agents were applied to the wound routinely by only 45 surgeons (26%), although 106 (61%) used them sometimes . Povidone-iodine was the agent most commonly used . Only 98 surgeons (56%) ever drained appendicectomy wounds, while 135 (77%) sometimes drained the peritoneal cavity . Evidence suggests that present methods of giving systemic antibiotic prophylaxis should continue, but that topical agents and surgical drainage are perhaps unnecessary when surgeons are confident of the efficacy of the systemic treatment used.

Nouv Presse Med, 1980 Dec 13, 9(47), 3615 - 20
{Penetration of antibiotics into the cerebrospinal fluid . Theoretical and practical aspects (author's transl)}; Modai J; The penetration of antibiotics into the cerebrospinal fluid (CSF) is governed by several factors, including lipid solubility, degree of ionization, pH gradient, serum protein binding, molecular weight and structure and, above all, degree of meningeal inflammation . The distribution within, and elimination from the subarachnoid spaces depend upon the physiology of the CSF and the route of administration of the drug . CSF penetration studies carried out in patients or volunteers with various groups of antibiotics and antibacterial agents have shown that, except for chloramphenicol and co-trimixazole, passage through the blood-brain barrier is generally poor . However, when the meninges are inflamed therapeutically active concentrations of penicillins and of some cephalosporins can be measured in the CSF.

Antibiotiki, 1980 Dec, 25(12), 932 - 5
{Effect of antibacterial preparations on carbohydrate hydrolysis and absorption in the small intestine}; Ishchuk IS et al.; The effect of levomycetin, phthalysulfathiazol, furazolidone and enteroseptal on hydrolysis and absorption of carbohydrates in the thin intestine of rabbits was studied . The level of sugar assimilation was estimated by the glycemia curves after differential loads with lactose, maltose, sucrose, glucose and galactose combination with glucose . The repressive effects of the chemotherapeutic drugs on both the parietal digestion of disaccharides and the adsorption of their monosaccharides was shown . Chloramphenicol lylsulfathiazol inhibited maltose hydrolysis, glucose adsorption and stimulated hydrolysis of lactose an absorption of its derivatives . Furazolidon and enteroseptal inhibited only lactose assimilation . The effect of the drugs on the intestine hydrolysis and absorption of the sugars depended to a significant extent on the individual host reaction.

Biochim Biophys Acta, 1980 Dec 1, 633(2), 289 - 94
A derivative of R-type cyanocobalamin binding proteins in the human intestine . A candidate antibacterial molecule; Marcoullis G et al.; Human jejunal fluid contains a protein which has a molecular radius of 3.37 nm, an Mr or 60600 and a mean pI of 3.35 and binds cobalamin with a K of 0.1 . 10(9) l/mol . This protein also couples cobalamin analogues lacking the nucleotide moiety, cross-reacts with R-type protein and is resistant to proteolysis in the intestine . These findings refute the hypothesis that cobalamin-analogue binders are present and effectively inhibit the bacterial uptake of analogues in the intestine.

Br J Exp Pathol, 1980 Dec, 61(6), 567 - 78
A morphological and histochemical study of a drug-induced enteropathy in the Alderley Park rat; Murgatroyd LB; Two experiments were devised to produce an experimental enteropathy . In Experiment I, male Alderley Park rats were dosed daily by gavage with 20 mg/kg and 60 mg/kg of an antibacterial compound ICI 17,363 . Animals were killed sequentially at daily intervals up to and including Day 9 to study the development of the enteropathy . In Experiment II rats were dosed daily with 60 mg/kg of the same compound . All animals were killed on Day 5 owing to a rapid development of the enteropathic condition . The duodenum was examined histologically and histochemically . Duodenal changes included vacuolation of columnar epithelial cells and villus stunting . There were marked reductions in mitotic activity in the crypt epithelial cells from Day 7 onwards (Experiment I) and almost total loss of hydrolytic and oxidative enzyme activity . In Experiment II the changes were more severe and haemorrhage and erosion of the duodenal mucosa were observed . The development of the enteropathic lesion appears to be due largely to the antimitotic effect of the compound, although a direct toxic effect upon the intestinal mucosa cannot be ruled out.

J Med Chem, 1980 Dec, 23(12), 1358 - 63
Structure-activity relationships of antibacterial 6,7- and 7,8-disubstituted 1-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids; Koga H et al.; Previous quantitative and qualitative structure-activity studies in antibacterial monosubstituted 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids prompted us to synthesize the 6,7,8-polysubstituted compounds . In this paper, the preparation and antibacterial activity of the 6,7- and 7,8-disubstituted compounds and their derivatives are described . Among these compounds, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)quinoline-3-carboxylic acid (34) possessed many significant activities and was more active than oxolinic acid (84) against Gram-positive and Gram-negative bacteria . Structure-activity relationships are discussed.

J Antibiot (Tokyo), 1980 Dec, 33(12), 1449 - 56
Dnacins, new antibiotics II . Isolation and characterization; Muroi M et al.; Dnacins A1 and B1, new basic antibiotics with strong and broad antibacterial activities, were isolated as dark red or reddish brown needles from the culture broth of Nocardia sp . No . C-14482 . The characteristic absorption maxima at 213 nm, 281 or 283 nm and 496 nm in the UV and visible range and other physicochemical properties indicated that dnacins A1 and B1 are novel antibiotics which belong to the group having aminobenzoquinone moieties.

J Antibiot (Tokyo), 1980 Dec, 33(12), 1407 - 16
A35512, a complex of new antibacterial antibiotics produced by Streptomyces candidus . II . Chemical studies on A35512B; Debono M et al.; The glycopeptide antibiotic A35512B was isolated from Streptomyces candidus NRRL 8156 as the major active factor . Chemical degradation studies showed that mild hydrolysis resulted in the release, one molecule each, of four neutral sugars: rhamnose, fucose, glucose and mannose, as well as the liberation of a complex peptide core which retained all the amino acids and from which 3-amino-2,3,6-trideoxy-3-C-methyl-L-xylo-hexopyranose, a new amino sugar, was isolated (2) . Oxidative degradation of A35512B resulted in the isolation of a chlorodiphenylether (5), dimethyl 4-methoxyisophthalate (7) and methyl 3,5-bis-(4-methoxycarbonylphenoxy(-4-methoxybenzoate (6) . The structure of 5 could not be conclusively elucidated but was shown to be either 5-chloro-2',3-dimethoxy-2,5'-dicarbomethoxy diphenylether (5a) or 2-chloro-2',3-dimethoxy-5,5'-dicarbomethoxy diphenylether (5b) by physical methods . This halogenated fragment was shown to arise from oxidation of constituent amino acid (10) which has the aromatic substitution pattern of fragment (5a or 5b) . Base hydrolysis resulted in the isolation of a phenanthridine (9) which arose from 2',4,6-trihydroxybiphenyl-2,5'-diyldiglycine . These chemical degradation studies on A35512B showed that this antibiotic is closely related to the ristocetin class of antibiotics.

J Antibiot (Tokyo), 1980 Dec, 33(12), 1397 - 406
A35512, a complex of new antibacterial antibiotics produced by Streptomyces candidus . I . Isolation and characterization; Michel KH et al.; The new antibiotic complex A35512 produced by Streptomyces candidus was isolated from the filtered fermentation broth . The individual factors A, B, C, E, and H were separated and purified by column chromatography . A35512B, the major factor, was isolated as the dihydrochloride salt, a white crystalline compound with an approximate empirical formula of C90H101 N8O39Cl.2HCl . The A35512 antibiotics belong to the glycopeptide class of antibiotics and possess high in vitro and in vivo activity against Gram-positive bacteria.

J Hyg (Lond), 1980 Dec, 85(3), 405 - 13
Bacteriostasis of Escherichia coli by milk . VI . The in-vitro bacteriostatic property of Gambian mothers' breast milk in relation to the in-vivo protection of their infants against diarrhoeal disease; Rowland MG et al.; PIP: A 1 year field study has been carried out in a diarrhea-endemic area in West Africa to determine the relationship between the bacteriostatic activity of fresh human milk for Escherichia coli in vitro and freedom from diarrhea of the infant recipients of the milk . The specific contribution of E . coli gastroenteritis to gastrointestinal diseases of infants in general is not known, nor is its particular role in the Gambian infants studied . During the study period, however, both enteropathogenic and toxigenic strains of E . coli were isolated . The incidence of diarrhea in Gambian infants of 7 age groups from 2 days-12 months was not significantly correlated with the bacteriostatic activity of milk . This was due rather to absence of diarrhea in babies fed on low-activity milk than illness in those receiving highly bacteriostatic milk . Indeed, very active milk appeared to protect recipients almost completely, including 7 babies of over 3 months of age, 5 of them during the rainy season, when the risk was high . Babies receiving lower-activity milk experienced more diarrhea . In a situation where diarrheal disease is multifactorial, field evaluation of the protective action by 1 antibacterial property of milk is difficult . A better understanding of in vivo protection is important, and the factors which have to be taken into account are discussed .

Nurs Clin North Am, 1980 Dec, 15(4), 833 - 42
Infection control for the burn patient; Marvin JA et al.; Infection control in the burn patient is dependent on the aseptic management of the wound and the environment of the patient, knowledgeable use of topical antibacterial agents, aggressive wound management, judicious use of systemic antibiotics, support of the deficient host defense system, maintenance of adequate nutrition, and close monitoring of laboratory and clinical signs of impending sepsis . With these key factors in mind, the nurses and physicians who care for burn patients can reduce the number of septic episodes as well as the morbidity and mortality associated with sepsis in the burn patient.

J Antibiot (Tokyo), 1980 Dec, 33(12), 1468 - 73
New anthracycline glycosides from Micromonospora . II . isolation, characterization and biological properties; Cassinelli G et al.; Four glycosides, designated A, B, C and D, are the main components of the anthracycline complex produced by cultures of Micromonospora sp . nov . They were extracted by solvent partition, separated by column chromatography and characterized by chemical and physical methods as 11-deoxy analogues of daunorubicin . Among these new anthracyclines, displaying antibacterial and cytotoxic activity in vitro, 11-deoxydaunorubicin and 11-deoxydoxorubicin are also active against P388 leukemia in mice.

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