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 metasta