Antimicrob Agents Chemother, 1990 Oct, 34(10), 1932 - 7 Comparative study of the effects of four cephalosporins against Escherichia coli in vitro and in vivo; van Ogtrop ML et al.; A thigh muscle infection induced with Escherichia coli in irradiated mice was used as a model to compare the in vivo pharmacodynamics of the antibacterial effect of four cephalosporins (i.e., cefepime, ceftriaxone, ceftazidime, and cefoperazone) with the in vitro antibacterial pharmacodynamics of these drugs . The following in vitro pharmacodynamic parameters were determined: the maximum effect as a measure for efficacy, the 50% effective concentration as a parameter for potency, and the slope of the concentration-effect relationship . For analysis of the in vivo antibacterial pharmacodynamics, the same parameters were applied for the dose instead of the concentration . For the detection of a relationship between concentration and antibacterial effect in vivo, we determined the pharmacokinetics of the four cephalosporins in the plasma of mice . The results showed that, in general, there is a direct relationship between the in vivo and in vitro pharmacodynamics of these cephalosporins . The maximum effects of cefepime, ceftazidime, and cefoperazone were approximately similar in vivo and in vitro . The sequence of potency of these drugs was, in descending order, cefepime, ceftazidime, and cefoperazone . Ceftriaxone differed from the other three cephalosporins in that it displayed unexpected in vivo pharmacodynamics . Ceftriaxone was just as efficacious as the other three in vitro, but its maximum effect in vivo was much lower . This relatively low maximum effect of ceftriaxone in vivo was not explained by the pharmacokinetic characteristics of the drug . From the present results it can be concluded that the in vitro efficacy of cephalosporins does not necessarily have a predictive value for the in vivo efficacy. Akush Ginekol (Mosk), 1990 Oct, (10), 11 - 5 {Abortion as a cause of maternal mortality}; Volgina VF et al.; PIP: The medical documents of 342 women who died as a result of abortion (induced, self-induced, and outside of hospitals) were analyzed . 24.2% of the women were under 24 years of age, 51.3% were 25-34 years old, and the rest were 35 or older . 69.9% of the women died after abortion outside of hospitals and the rest after self-induced and induced abortions . 65.8% of the women were pregnant at 13-27 weeks of gestation . The death of 186 of 238 women was due to abortions performed outside of hospitals . Most of these were the result of invasive methods (the introduction of the catheter, solutions, rupture of the amniotic sac) . These women subsequently received medical assistance . 93.3% of them were hospitalized with delay, and only 2.6% were admitted in satisfactory condition . In a significant proportion of patients the examination was belated and inadequate . Various laboratory hematological tests that were essential for diagnosis and determination of the severity of the process were not done . The bacteriological tests to select the appropriate antibacterial drug were rarely performed--the tests were done for only 19.8% of women who had died of sepsis and for 14.3% of those who had died of peritonitis . Inadequate care manifested itself in the fact that diagnosis was established for only 46.8% of patients . Sepsis and peritonitis were the cause of death for 73.9% of all women and for 88.6% of those who died of abortion outside the hospital . Hemorrhage was the second most frequent cause, with 42 women dying because of it . Other causes were anaphylactic shock and thromboembolism of the pulmonary arteries . The elimination of such causes of death mandate goal-oriented preventive measures accompanied by diagnosis and therapy and the raising of the knowledge level of the medical personnel about purulent-septic infections . A radical improvement in bacteriological care also must be effected . Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Oct, 28(10), 1305 - 13 {Long-term therapeutic effects of erythromycin and newquinolone antibacterial agents on diffuse panbronchiolitis}; Yamamoto M et al.; The present study reviewed and summarized the long-term therapeutic effects of erythromycin or newquinolone antibacterial agents on diffuse panbronchiolitis . Various parameters before and after the treatment were analyzed in 101 patients selected from 227 diffuse panbronchiolitis patients gathered from 26 institutes in Japan . Patients had been treated with either erythromycin or newquinolone antibacterial agent for more than 3 months . Patients treated with erythromycin showed significant improvement of dyspnea on exertion, findings of chest X-ray, data on blood gas analysis, rate of ESR, titer of cold coagulation and amount of sputum, compared with patients treated with the newquinolone antibacterial agent . Among the patients treated with erythromycin, those patients with the initial high cold coagulation titer showed better improvement following treatment . However, there was no significant difference in improvement, depending upon either the duration between the time of onset of the disease, the initiation of treatment, and the initial severity of the disease. Br J Clin Pract, 1990 Oct, 44(10), 404 - 8 Comparison of oral erythromycin ethylsuccinate and ciprofloxacin in the treatment of acute respiratory tract infections; Feld MS et al.; A total of 619 patients with acute upper or lower respiratory tract infection were randomised to receive either erythromycin ethylsuccinate tablets at a dose of 1 g twice daily, or ciprofloxacin tablets 500 mg twice daily in a single-blind, multicentre study . The efficacy of each antibacterial was similar, with close to 90% of patients on each treatment being reported as either cured or improved . Gastrointestinal symptoms were the most commonly reported side-effects, being similar in overall incidence for both agents . Nausea, vomiting, dizziness and headache occurred more frequently in the ciprofloxacin group, while abdominal pain and diarrhoea occurred more frequently in the erythromycin ethylsuccinate group . In each group, the number of patients failing to complete treatment was similar and the main reasons cited for discontinuation were gastrointestinal symptoms . This study indicates that both erythromycin ethylsuccinate and ciprofloxacin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections. Rozhl Chir, 1990 Oct, 69(10), 668 - 73 {Cefuroxime axetil (Zinnat)--laboratory and clinical study}; Vyhnanek F et al.; The authors investigated the antibacterial action of cefuroxim in vitro and proved its relatively broad spectrum of action . Administration of the esterified form, Zinnat, produced very satisfactory therapeutic concentrations of cefuroxim in serum, bile tissue of operated gallbladders . The prophylactic administration of the combined parenteral and oral form of cefuroxim proved excellent in biliary surgery in twenty patients. J Antimicrob Chemother, 1990 Oct, 26 Suppl B, 167 - 72 Prospective randomized comparison of pefloxacin and ampicillin plus gentamicin in the treatment of bacteriologically proven biliary tract infections; Chacon JP et al.; One hundred and eighty-nine patients with acute cholecystitis or cholangitis requiring antibacterial therapy and surgery were randomly allocated in a prospective open study to receive either iv or oral pefloxacin (800 mg per day) or a combination of iv or oral ampicillin (4 g per day) and gentamicin (240 mg per day im) . Ninety-two patients had to be withdrawn from the efficacy analysis, mainly because of negative baseline culture, but occasionally because of isolation of bacteria resistant to the study drugs . In the 97 evaluable patients (90 with cholecystitis and 7 with cholangitis) the clinical cure rates were excellent and similar for both groups: 49/50 (98%) for pefloxacin and 45/47 (95.7%) for the combination; the respective bacteriological success rates were 100% and 91.5% . Three patients in the pefloxacin group and six patients in the ampicillin-gentamicin group reported mild and transient side effects. J Trauma, 1990 Oct, 30(10), 1267 - 72 Splenectomy influences endotoxin-induced bacterial translocation; Spaeth G et al.; To determine whether splenectomy affects the antibacterial defenses of the gut, experiments were performed using bacterial translocation (BT) as a marker of intestinal barrier failure . The incidence of BT was measured 8 days after splenectomy or sham-splenectomy in mice receiving or not receiving endotoxin (0.1 mg IP) . Splenectomy does not appear to promote BT from the gut, since the incidence of bacterial translocation after splenectomy or sham-splenectomy (5%) were not different . A second experiment was performed to determine whether the resistance to endotoxin-induced BT was modified after splenectomy . The incidence of endotoxin-induced BT was 73% in the unoperated control group, 59% in the sham-splenectomy group, but 23% in the splenectomy group (p less than 0.002) . Thus, splenectomy but not sham-splenectomy increased the resistance of otherwise healthy mice to endotoxin-induced BT. Am J Hum Genet, 1990 Oct, 47(4), 686 - 97 Alleles at the PRB3 locus coding for a disulfide-bonded human salivary proline-rich glycoprotein (Gl 8) and a null in an Ashkenazi Jew; Azen EA et al.; From electrophoretic analysis, we identified in the saliva of an Ashkenazi Jew a disulfide-bonded major glycoprotein variant (Gl 8) that is a product of the proline-rich protein (PRP) locus PRB3 . A previous study of this variant protein misidentified it as Pa 2 and as a product of a different PRP locus . The other PRB3 allele in this individual is an apparent null . To identify the mutations, we sequenced the tandemly repetitious exon 3 (the major protein-coding portions) of both alleles . A CGT----TGT (Arg----Cys) mutation was found in one allele (PRB3Scys), which accounts for the disulfide-bonded and peroxidase-modifying properties of Gl 8 . A single nucleotide insertion was found in the other allele (PRB3Mnull) that leads to a frameshift with a premature termination codon that causes an apparent lack of gene expression . Null alleles are frequent at PRP loci coding for basic and glycosylated PRPs, and the mechanism described might explain other null phenotypes among PRPs . From nucleotide comparisons, a model of intragenic unequal crossing-over is proposed to explain, in part, the generation of the PRB3Mnull allele . The Gl 8 protein variant is found in Ashkenazi Jews (gene frequency around .008) but not in the general white, black, or Japanese populations . It is interesting that products of different PRP genes, Gl 8 from PRB3 and Pa 1 from PRH1, are both disulfide bonded and probably modify salivary peroxidase (part of an important intraoral antibacterial system) through formation of disulfide-bonded heterodimers. Scand J Dent Res, 1990 Oct, 98(5), 422 - 7 Further in vivo studies on the plaque-inhibiting effect of chlorhexidine and its binding mechanisms; Waaler SM; The aim of the present study was to investigate the relative importance of chemical groups in the oral cavity which bind chlorhexidine of clinical significance . This was performed by clinical experiments where a test panel of 11 individuals rinsed with chlorhexidine at pH 7, pH 5.5, and pH 3 . Rinsing with 0.02 M EDTA was performed prior to the chlorhexidine rinse, because this procedure has been shown to enhance the antibacterial effect of chlorhexidine in vitro . However, pre-rinses with EDTA did not increase the clinical effect of chlorhexidine . Bacteriologic tests showed comparable antibacterial effect of chlorhexidine at pH 7 and pH 3 . Mouthrinses of pH 7 and pH 5.5 had comparable plaque-inhibiting effects, whereas the effect of a rinse of pH 3 was not different from that of the placebo . This finding is interpreted to suggest that primary phosphate (pK about 2) is an important receptor site for chlorhexidine, whereas secondary phosphate (pK = 7.0) is of negligible importance . Previous studies have clearly shown that phosphate binds chlorhexidine . The lack of clinical effect at pH 3 is probably due to precipitation of salivary proteins by hydrogen ions, making primary phosphate groups unavailable for interaction with chlorhexidine. J Antibiot (Tokyo), 1990 Oct, 43(10), 1278 - 85 Synthesis and antibacterial activity of 7 beta-{1-(2-aminothiazol-4-yl)-1-cyclopropanecarboxyamido}cephem derivatives; Nishimura S et al.; The synthesis and antibacterial activity of several 7 beta-{1-(2-aminothiazol-4-yl)-1-cyclopropanecarboxyamido}cep hem derivatives (1) are described . The structure-activity relationships of 1 are also presented. Vestn Khir Im I I Grek, 1990 Oct, 145(10), 70 - 2 {Prevention of suppurative complications after closure of formed intestinal fistulas in children}; Biriukov AV et al.; The problem of prophylactics of postoperative infectious complications in the surgery of digestive tract is discussed . A comparative analysis of efficiency of two methods of antibacterial prophylactics during operations of closing the formed intestinal fistulas in children is given . High efficiency of the method of preoperative subtotal decontamination of the intestine according to individually selected schemes is shown. Antimicrob Agents Chemother, 1990 Oct, 34(10), 1955 - 60 Inhibitory effects of quinolones on pro- and eucaryotic DNA topoisomerases I and II; Moreau NJ et al.; As a means of gaining information on the selectivity of quinolone antibacterial agents, we examined their effect on four topoisomerases, topoisomerases I and II purified from Escherichia coli and calf thymus . The inhibition of supercoiling and relaxation activities was monitored by using the classical gel electrophoresis assay . Eight quinolones were assayed by using the four enzymes . Gyrase was much more sensitive to quinolones than the other topoisomerases which can therefore be inhibited by moderate concentrations of certain quinolones . No good correlation was observed between the activity on gyrase and on the other enzymes, since the ratio varied from 15 to more than 8,500 . On the contrary, there was a good correlation between early inhibition of DNA synthesis, inhibition of gyrase, and MICs. FEBS Lett, 1990 Sep 3, 269(2), 413 - 20 1H nuclear magnetic resonance study of the solution conformation of an antibacterial protein, sapecin; Hanzawa H et al.; The solution conformation of an antibacterial protein sapecin has been determined by 1H nuclear magnetic resonance (NMR) and dynamical simulated annealing calculations . It has been shown that the polypeptide fold consists of one flexible loop (residues 4-12), one helix (residues 15-23), and two extended strands (residues 24-31 and 34-40) . It was found that the tertiary structure of sapecin is completely different from that of rabbit neutrophil defensin NP-5, which is homologous to sapecin in the amino acid sequences and also has the antibacterial activity . The three-dimensional structure determination has revealed that a basic-residue rich region and the hydrophobic surface face each other on the surface of sapecin. Pol Tyg Lek, 1990 Sep 3-10, 45(36-37), 749 - 51 {Netilmicin in the treatment of bacterial respiratory tract infections}; Wandzilak M et al.; Netilmicin - a semisynthetic aminoglycoside - was administered to 33 patients with the acute or chronic lower respiratory tract or pulmonary infections in a daily dose of 5 mg/kg body weight for 10 days . A principle criterium of patients classification to netilmicin therapy were sensitive bacterial strains either in sputum or in BAL liquid . A significant clinical improvement was noted in 88% of the treated patients . However, elimination of pathogens from the sputum was achieved only in 52% of these patients . No improvement was observed in 4% of the treated patients . No adverse reactions were noted . Netilmicin proved safe and effective antibacterial agent in patients with respiratory infections. Equine Vet J Suppl, 1990 Sep, (10), 18 - 21 Peripheral corneal ulcers in the horse; Dice PF et al.; This report involves a retrospective study of five horses with an unusual form of progressive peripheral corneal ulcers . These ulcers were located at the perilimbal region of the cornea and spread both centripetally to mid periphery and circumferentially . Lipping of the epithelial edge was observed often . The depth ranged from superficial to mid stroma . Patients ranged from two and a half to eight years, both sexes, and were referred after a variety of antibacterial therapy . Histories were similar in that all ulcers were initially located adjacent to the limbus in one or more quadrants . No trauma was known to antedate the corneal disease and the patients were in good general health . Conjunctivectomy was performed in three patients which revealed an abundance of plasma cells and lymphocytes . All five cases were negative for a specific bacterial pathogen . Patients responded to a variety of treatment modalities: topical corticosteroid, surgical debridement, therapeutic soft contact lens (TSCL), and/or conjunctivectomy. Anesteziol Reanimatol, 1990 Sep-Oct, (5), 66 - 7 {A case of the successful treatment of an 11-year-old child with a fulminating form of tetanus}; Egorov VM et al.; A case of a successful treatment of a patient with an extremely severe tetanus form is described . The management of the patient included massive specific antibacterial and infusion therapy, hemoperfusion, standard and high frequency controlled lung ventilation . The problems of patient activation and respiration recovery have arisen in the course of treatment . They were dealt with, using hemoperfusion that reduced the residual effect of sedative agents and myorelaxants, as well as high frequency jet ventilation, which accelerated respiration recovery. Antimicrob Agents Chemother, 1990 Sep, 34(9), 1637 - 41 In vitro selection of resistant Helicobacter pylori; Haas CE et al.; Four strains of Helicobacter pylori were subjected to an in vitro serial passage technique to compare the propensity of the organisms to develop resistance to seven classes of antibacterial agents . The passages were made on serially doubling concentrations of antibacterial agents incorporated into agar starting at one-half the base-line MIC . The frequency of spontaneous resistance was also determined for each strain at four and eight times the MIC of each antibacterial agent . Strains resistant to ciprofloxacin, metronidazole, erythromycin, and tobramycin were isolated . The experiments failed to select organisms resistant to bismuth subsalicylate, furazolidone, or amoxicillin, although the MIC of amoxicillin was increased 4- to 16-fold . With the exception of erythromycin, organisms with the selected resistance were stable after at least three passages on antibacterial agent-free medium . Spontaneous resistance rates were generally of a low magnitude and were not predictive of the serial passage results. Vrach Delo, 1990 Sep, (9), 51 - 3 {The diagnostic significance of the test for spontaneous blood neutrophil damage in acute myeloid forms of leukemia}; Guseva SA; Spontaneous lesioning of neutrophils (SLN) cultured in a saline solution was studied in 75 patients with acute myeloid leucosis . Results indicate a significant increase of the SLN number in the group of patients with the presence of infectious complications . It is recommended to use the SLN test as a criterion of diagnosis and efficacy of antibacterial treatment of infectious complication in patients with acute myeloid leucosis. Pharmazie, 1990 Sep, 45(9), 688 - 9 {Synthesis and action of 1-n-hexyl-2-phenyl-3-(n-alkoxymethyl)- and 1-n-hexyl-2-phenyl-3-(6-n-alkylthiomethyl)imidazolium chlorides}; Pernak J et al.; The synthesis of quaternary imidazolium chlorides was performed by reaction of 1-n-hexyl-2-phenyl-imidazole with chloromethylalkyl ether or chlormethylalkyl sulfide . The antibacterial properties of the compounds obtained was tested on 13 strains of bacteria and fungi . Chlorides with octyl- and decylthiomethyl moiety indicated the best antibacterial activity. Stomatologiia (Mosk), 1990 Sep-Oct, (5), 24 - 6 {The use of an ortofen-containing paste in the combined treatment of periodontal diseases}; Dotsenko EV et al.; A periodontal dressing for the treatment of gingivitis and periodontitis, characterized by antiinflammatory and antibacterial action, was developed and clinically tried . Application of this dressing cut down the periods of treatment of chronic gingivitis and periodontitis, shortens the period of preparation to surgery, and provides a smooth course of the postoperative period. Antibiot Khimioter, 1990 Sep, 35(9), 40 - 2 {Antibiotic binding by leukocytes from brucellosis patients}; Nigmatulin AZ et al.; Antibiotic binding by leukocytes from patients with chronic brucellosis was studied in vitro . The pathogens were located intracellularly . The specimens were collected during the disease aggravation prior to the treatment and at the beginning of the remission after the routine therapy . It was found that during the disease aggravation at the intoxication peak and accumulation of a large number of Brucella in the cells binding of methacycline, rifampicin and gentamicin somewhat increased . After completion of the treatment course when the number of Brucella in the leukocytes markedly lowered, up to disappearance, the antibiotic binding decreased and reached the control figures . Penetration of erythromycin into the cells infected with Brucella lowered at the disease peak and remained at that level with an insignificant tendency to normalization at the beginning of the clinical remission after the treatment . The facts suggested that intracellular localization of the bacteria would change the quantitative characteristics of interaction of the cells, i.e . human leukocytes with antibacterial chemotherapeutic agents . The direction of the shifts must depend on the particular proportion of various types of mechanisms for penetration of drugs into the intracellular medium. Antibiot Khimioter, 1990 Sep, 35(9), 14 - 7 {Taxonomic spectrum of pathogens of mixed infections in oncology patients and principles of their antibacterial therapy}; Smolianskaia AZ et al.; Mixed infections were observed in oncological patients irrespective of the tumor or infectious process localization . 25-30 per cent of the pathological materials from such patients were contaminated with bacterial associations . The number of the associates ranged from 2 to 5 depending on the pathological material tested . Therapy of infectious complications due to pathogen associations should stem from analysis of many factors, i.e . properties of the isolated or likely pathogens, individual characteristics of the patients, compatibility of the drugs used and their pharmacokinetic features. J Antimicrob Chemother, 1990 Sep, 26 Suppl A, 1 - 10 Serum protein binding and extravascular diffusion of methoxyimino cephalosporins . Time courses of free and total concentrations of cefotaxime and ceftriaxone in serum and pleural exudate; Scaglione F et al.; A new approach to the study of the distribution pharmacokinetics of variably bound beta-lactams is to plot the concentration time course of their free (dialysable) and total (free and bound) forms . In the present study, the 6-h concentration time course was plotted of the total and free concentrations of cefotaxime and ceftriaxone in serum and pleural exudate in 12 patients per group, after iv dosing with 1 g of either cefotaxime or ceftriaxone . Samples were taken at 0.5, 1, 1.5, 2, 3, 4 and 6h after dosing . The results of a study of similar design, but conducted over 24 h in ten patients per group, following iv dosing with either cefotaxime 1 g 12-hourly or ceftriaxone 1 g daily are also reported . Samples were taken at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 14, 16 and 24 h after dosing . Areas under the curve of free cefotaxime in pleural fluid were greater than those of free ceftriaxone, in both the 6 h (+54.6%) and 24 h studies (+29.8% after 12 h and +71.0% after 24 h) . The free cefotaxime/free ceftriaxone Cmax ratio was 1.75 in the 6 h study . Cefotaxime was superior to ceftriaxone in terms of the diffusion of the free (antibacterially active) fraction into a typical inflammatory exudate . Assessment of the effects of protein binding must be taken into account in antibiotic pharmacokinetic profiles. J Antibiot (Tokyo), 1990 Sep, 43(9), 1160 - 8 Synthesis and biological activity of 3-vinylthio- and 3-vinylthiomethylcephem derivatives; Nishimura S et al.; The synthesis and biological properties of some 3-vinylthio- and 3-vinylthiomethylcephem derivatives are described . Both series possess potent antibacterial activity . Among them, 3-{(Z)-2-cyanovinylthiomethyl}cephem derivative was found to have an expanded antibacterial spectrum. J Antibiot (Tokyo), 1990 Sep, 43(9), 1137 - 49 Synthesis and antibacterial activity of C-2 alkenylthio-carbapenem derivatives; Corbett DF et al.; A number of C-2 aminoalkenylthio-carbapenem derivatives possessing both the (5R,6R, 8S)- and the (5R,6S,8R)-stereochemistries have been prepared from the olivanic acids MM 22382 and MM 22383, respectively . Certain members of this new class of compounds displayed potent, broad spectrum antibacterial activity as well as improved stability to human kidney homogenate. J Antibiot (Tokyo), 1990 Sep, 43(9), 1089 - 97 Synthesis and biological activity of some amide derivatives of the lantibiotic actagardine; Malabarba A et al.; A series of basic carboxamides of actagardine (1), a lantibiotic possessing good antistreptococcal activity, were synthetized . Some physico-chemical characteristics, in particular charge and lipophilicity, that influence water solubility were determined . The in vitro and in vivo activity was evaluated . The monocarboxamides were generally more active than actagardine against selected Gram-positive bacteria . The 3,3-dimethylamino-1-propylamide hydrochloride (4) showed good water solubility, bactericidal action and favourable antibacterial activity and it appears to be a suitable drug for further investigation. J Antibiot (Tokyo), 1990 Sep, 43(9), 1059 - 63 Simaomicin (LL-D42067), a novel antibiotic from Actinomadura madurae . I . Taxonomy, fermentation and biological activity; Maiese WM et al.; A new antibacterial antibiotic, designated simaomicin alpha (LL-D42067 alpha) was isolated from the fermentation broth of an actinomycete strain . Based on cultural, physiological, morphological and chemical characteristics, culture LL-D42067 was identified as a new subspecies of Actinomadura madurae . Simaomicin alpha demonstrated potent activity against Gram-positive bacteria and was active in vivo against a variety of Eimeria species causing coccidiosis in chickens. Int J Lepr Other Mycobact Dis, 1990 Sep, 58(3), 503 - 11 Sequential monitoring of leprosy patients with serum antibody levels to phenolic glycolipid-I, a synthetic analog of phenolic glycolipid-I, and mycobacterial lipoarabinomannan; Meeker HC et al.; Sequential serum samples from leprosy patients at various stages of antibacterial treatment were tested by an ELISA for antibodies to phenolic glycolipid I (PGL-I), a synthetic PGL-I analog (ND-BSA), and lipoarabinomannan (LAM) from Mycobacterium tuberculosis to determine if these antibodies could be useful in monitoring response to therapy . Among patients with positive initial anti-PGL-I IgM, a significant decrease in this antibody was seen over time (p less than 0.01), whether assayed by PGL-I or ND-BSA . The two antigens showed good agreement in the detection of decrease in anti-PGL-I IgM . The greatest decrease was seen in patients with a high initial anti-PGL-I IgM and a high bacterial index (BI) . Patients with a declining BI were seen to have generally declining antibody levels to PGL-I and to LAM; in those patients with a fluctuating BI, antibody levels were less predictable . We conclude that antibodies to PGL-I and LAM can be useful in following response to therapy in leprosy patients and that either the native PGL-I or ND-BSA can serve as antigen for the ELISA. Chem Pharm Bull (Tokyo), 1990 Sep, 38(9), 2459 - 62 Studies on antibacterial agents . II . Synthesis and antibacterial activities of substituted 1,2-dihydro-6-oxo-6H-pyrrolo{3,2,1-ij}quinoline-5-carboxylic acids; Ishikawa H et al.; A series of substituted 1,2-dihydro-6-oxo-pyrrolo{3,2,1-ij}quinoline-5-carboxylic acids for the treatment of systemic infections was synthesized via 7-bromo-3-ethylthio-4,5-difluoro-2-methylindole (3), which was prepared by Gassman's indole synthesis in excellent yield . The synthesized pyrroloquinolines were tested for their antibacterial activities . 8-Fluoro-1,2-dihydro-2-methyl-9-(4-methyl-1-piperazinyl)-6-oxo-6H- pyrrolo{3,2,1-ij}quinoline-5-carboxylic acid showed a potent antibacterial activity against gram-positive and gram-negative bacteria. Haematologica, 1990 Sep-Oct, 75(5), 454 - 63 Haematologic abnormalities in the acquired immunodeficiency syndrome; Brizzi MF et al.; During the clinical history of HIV infection, haematological abnormalities represent a common finding which not only contributes to worsening the clinical condition but also limit the use of antibacterial as well as antiviral agents . On the basis of the regulatory role played by the immune system on haemopoiesis, in the present review the foremost derangements of the immunoregulatory circuits are first discussed . The main functional and quantitative defects of peripheral blood erythrocytes, granulocytes, platelets and monocytes are then analysed, and the different bone marrow pictures observed during the progression of the disease are described . To elucidate the physiophatogenetic mechanisms responsible for bone marrow and peripheral cytopenia, the most relevant in vitro studies are reported and discussed . These studies suggest that both a direct cytopathic effect of HIV on haemopoietic progenitors and an immune system mediated mechanism are involved . In view of the HIV selective tropism for lymphocytes and macrophages, which are a major source of haemopoietic growth factors, the new therapeutical strategies for the treatment of cytopenias based on exogenous administration of these cytokines, alone or in combination with antiviral drugs, are briefly reported. Am J Dent, 1990 Sep, 3 Spec No, S7 - 14 Antiplaque effects of dentifrices containing triclosan/copolymer/NaF system versus triclosan dentifrices without the copolymer; Gaffar A et al.; A dentifrice containing triclosan/PVM/MA, Colgate Gum Protection Formula Toothpaste (GPF), was found to be highly effective against oral bacteria with minimal inhibitory concentration ranging from 0.3 to 5.35 micrograms/ml . A variety of in vitro model systems simulating oral environment were used to compare dentifrices containing triclosan/PVM/MA versus the dentifrices containing triclosan without PVM/MA, such as Crest Gum Health Toothpaste (CGH) and Neo-Mentadent P Toothpaste (N-MP) . The uptake of triclosan on saliva-coated hydroxyapatite (HA) disks and buccal epithelial cells was significantly higher from the GPF versus the other dentifrices . Uptake on HA disks was 132 micrograms/disk versus 11 micrograms/disk from CGH; on buccal epithelial cells the uptake was 59 micrograms/2 x 10(5) cells with GPF versus 30.0 micrograms with CGH per same number of cells . The retained triclosan on the surfaces provided a sustained and higher antibacterial effect up to 4 hours post-treatment with GPF, but not with N-MP and CGH . In dynamic plaque model systems such as the chemostat or the controlled saliva flow system, GPF was significantly (P = 0.05) more effective than N-MP or CGH in reducing plaque thickness, protein and carbohydrate contents of plaque films . Collectively, the results of these microbiological and biochemical investigations indicate that the GPF has the potential to provide superior clinical efficacy versus the dentifrices without the copolymer. Vopr Med Khim, 1990 Sep-Oct, 36(5), 21 - 4 {Guanylate cyclase from human platelets in pulmonary tuberculosis}; Riaposova IK et al.; Activity of soluble guanylate cyclase and activating effect of sodium nitroprusside were studied in thrombocytes of patients with infiltrative form of pulmonary tuberculosis before treatment (as soon as patients entered the hospital) and within various periods of the antibacterial therapy course: during the first month, 1.5-2, 2.5-3.5 and more than 4 months of treatment . Before treatment activity of guanylate cyclase in the patients thrombocytes was similar to that of donors independently on severity of the process in lungs (impairment of more or less two lung segments) . During the antibacterial therapy the enzyme activation was detected, which reached 160% of the normal level within 2 months course and decreased down to the control rate within 4 months of treatment . The activating effect of sodium nitroprusside was distinctly decreased (by 70%) in thrombocytes of patients with infiltrative form of pulmonary tuberculosis before the treatment course, while the pattern was restored to the normal level, comparable with control values in donors, within 4 months of the treatment . The stimulating effect of sodium nitroprusside on guanylate cyclase activity in thrombocytes of patients with infiltrative form of pulmonary tuberculosis may be used as an additional criterion for evaluation of the therapeutic course efficiency. Schweiz Rundsch Med Prax, 1990 Aug 21, 79(34), 976 - 82 {Typhoid fever}; Losse H; The second part of this review accounts on a patient with classic symptoms of typhoid fever . The case history is commented in the light of todays knowledge . The case was taken from the clinical notes of Schonlein one of the most famous clinicians of the first part of the 19th century . It reveals the difficulties of the physician to cope with such a disease without our present diagnostic and therapeutic possibilities . It is surprising to realize that 150 years ago therapy of typhoid fever was not substantially different from that in use up to the recent introduction of specific antibacterial therapy . Since the typical course of typhoid fever is only rarely encountered nowadays the case seems suitable to recall this clinical picture to our generation of physicians. J Med Chem, 1990 Aug, 33(8), 2270 - 5 Quinolone antibacterial agents substituted at the 7-position with spiroamines . Synthesis and structure-activity relationships; Culbertson TP et al.; A series of fluoroquinolone antibacterials having the 7-position (10-position of pyridobenzoxazines) substituted with 2,7-diazaspiro{4.4}nonane (4b), 1,7-diazaspiro{4.4}nonane (5a), or 2,8-diazaspiro{5.5}undecane (6b) was prepared, and their biological activities were compared with piperazine and pyrrolidine substituted analogues . Most exhibited potent Gram-positive and Gram-negative activity, especially when side chain 4b was N-alkylated. EMBO J, 1990 Aug, 9(8), 2507 - 15 Insect immunity: expression of the two major inducible antibacterial peptides, defensin and diptericin, in Phormia terranovae; Dimarcq JL et al.; Injections of low doses of bacteria into larvae of Phormia terranovae induce the appearance of potent bactericidal peptides in the blood, among which predominate the anti-Gram positive insect defensins and the anti-Gram negative diptericins . Insect defensins show significant homologies to mammalian (including human) microbicidal peptides present in polymorphonuclear leukocytes and macrophages . We report the molecular cloning of cDNAs and primer extension studies which indicate that insect defensin is produced as a prepro-peptide yielding mature defensin A (40 residues) after cleavage of a putative signal peptide (23 residues) and a prosequence (34 residues) . Previous studies have established that diptericin (82 residues) is matured from a pre-peptide by cleavage of a putative signal peptide (19 residues) and C-terminal amidation . Using oligonucleotide probes complementary to the sequences of the mRNAs for defensin and diptericin, we show by in situ hybridization that both antibacterial peptides are concomitantly synthesized by the same cells: thrombocytoids, a specialized blood cell type, and adipocytes . Transcriptional studies based on hybridization of RNAs to cDNAs of defensin and diptericin indicate that the transcription of both genes is induced regardless of the nature of the stimulus (injection of Gram positive or Gram negative bacteria, lipopolysaccharides) . Even a sterile injury applied to axenically raised larvae is efficient in inducing the transcription of both genes suggesting that the local disruption of the integument aspecifically initiates a signalling mechanism which the thrombocytoids and the adipocytes are able to interpret . The transcription of immune genes is relatively short lived and a second challenge yields a response similar to that of the first stimulus, indicating that the experimental insects do not keep a 'memory' of their first injection. Antibiot Khimioter, 1990 Aug, 35(8), 37 - 9 {Rapid evaluation of the effectiveness of antibacterial drugs in experimental tularemia}; Oborin VA et al.; Rapid estimation of the protective effect of antibacterial drugs on Fransiella tularensis for not more than 2 days was shown possible in experiments on albino mice infected with tularemia . High efficacy of aminoglycosides (kanamycin, gentamicin, streptomycin, amikacin, netilmicin, tobramycin, sagamycin, ribostamycin and sisomicin), tetracyclines (tetracycline, doxycycline, minocycline and methacycline), rifampicin, phosphomycin and oxolinic acid was determined with the recommended rapid method . Amoxycillin, ampicillin, piperacillin, carbenicillin, erythromycin, levomycetin, cefradine, cefmetazole, cefatrizine, cefoxitin, cefsulodin and bactrim (biseptol) proved to be inefficient against the tularemia causative agent. Antibiot Khimioter, 1990 Aug, 35(8), 35 - 7 {Comparative study of the effectiveness of amikacin and streptomycin in experimental tularemia}; Tynkevich NK et al.; In vitro study on antibacterial activity of amikacin in comparison to that of streptomycin revealed a high sensitivity of tularemia microbes of three geographical races to it . Amikacin showed a high therapeutic activity in treatment of albino mice infected with tularemia . The prospects of amikacin use in prophylaxis and treatment of tularemia are defined by its antibiotic activity against streptomycin-resistant forms of the tularemia causative agent. Dan Med Bull, 1990 Aug, 37(4), 375 - 7 Prescribing in hospital outpatient departments and rural health facilities in Uganda: some clinical and educational implications; Christensen RO et al.; A comparison of prescribing patterns in hospital outpatient departments (OPD) and rural health units (RHU) in Uganda revealed an average of 2.45 and 1.66 drugs prescribed per treatment episode in OPD and RHU respectively . 40.1% of the OPD and 57.3% of the RHU prescriptions included antibacterials . It is argued that in view of the relevant morbidity pattern, an average of 1.4-1.5 drug/treatment episodes, as well as 15-20% receiving antibacterials would seem appropriate, thus leaving scope for considerable cost reductions . A successful strategy for achieving rational prescribing is likely to include a variety of educational approaches aimed at all present and future prescribers. Planta Med, 1990 Aug, 56(4), 364 - 7 Growth, terpenoid production and antibacterial activity of an in vitro culture of the liverwort Fossombronia pusilla; Sauerwein M et al.; In vitro cultures of the liverwort, Fossombronia pusilla, have been ititiated from spores . They grew well on Gamborg B5 medium supplemented with 2% saccharose and 12.5 micrograms/l vitamin B12 . Undifferentiated cultures were obtained on Knop mineral solution with 4% glucose . The cultures produced the same constituents as collected material . Perrottetianal A and B, known substances from liverworts were isolated and characterized by spectroscopic methods as well as alpha-(-)-santonin . A hitherto unknown diterpene dialdehyde-8-hydroxy-9-hydroperrottetianal A--could also be characterized . Furthermore, 7 terpenes were identified by GC/MS . A petrol ether extract and the isolated terpenes exerted antibacterial activity. Nippon Hinyokika Gakkai Zasshi, 1990 Aug, 81(8), 1240 - 6 {Follow-up of 104 children with "primary" VUR . Incidence of unstable bladder, its impact on resolution of VUR and progression of renal scar}; Kakizaki H et al.; One hundred and four children (48 boys and 56 girls, ranging in age from 3 months to 15 years, and follow-up period of more than 2 years in all) with "primary" vesicoureteral reflux (VUR) were retrospectively analyzed with particular emphasis on resolution of VUR and occurrence of renal scar . All underwent cystoscopic examinations which failed to demonstrate any organic vesicourethral obstruction, and all were neurologically normal . The patient population was divided into 2 groups based on cystometric findings . Group 1 consisted of 74 patients with unstable bladder and Group 2 consisted of 30 patients without unstable bladder . Although both groups were initially kept under antibacterials, in Group 1 frequent voiding and anticholinergics were maintained until the bladder stabilized by itself . There was no difference in the grade of reflux between the two groups . The rate of spontaneous resolution of reflux was 18% in group 1 in which more than 60% of the patients were with high grade reflux, while in Group 2 it was 17%, similarly to Group 1, but all were with low grade reflux . The presence or absence of renal scar and its subsequent evolution were determined in 73 patients in whom serial urograms were available enough to evaluate nephrographic renal outline . The incidence of renal scar at the first visit was 26% in Group 1 and 36% in Group 2 . New formation of renal scar was not found in either group . The progression of preexisting renal scar was seen only in Group 1 (5/55 patients, 9%), and not in Group 2 (0/18 patients, 0%).(ABSTRACT TRUNCATED AT 250 WORDS) FEMS Microbiol Lett, 1990 Aug, 58(3), 311 - 6 Simultaneous exploitation of different peptide permeases by combinations of synthetic peptide smugglins can lead to enhanced antibacterial activity; Smith MW et al.; Various synthetic, peptide prodrugs (smugglins) were tested alone and in combination for activity against Escherichia coli . The smugglins may be transported through any of three peptide permeases, and once inside the bacteria are activated by intracellular peptidase action to release their intrinsically impermeant, antibacterial moieties . When each such antibiotic peptide present in a mixture was accumulated via a different permease, synergistic effects could be observed . Synergy was also found when smugglins were combined with other non-peptide antibiotics . The principle of using smugglin combinations could extend the scope of their application, and should minimise the potential problem that can arise from the occurrence of resistant, transport mutants . The smugglin interactions were studied using a modified microtitre plate assay. Antimicrob Agents Chemother, 1990 Aug, 34(8), 1512 - 4 Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells; Raoult D et al.; There is no consistently reliable treatment for endocarditis resulting from chronic Coxiella burnetii infection, the causative agent of Q fever . Although certain antibiotics are recommended on the basis of their in vitro bactericidal activities, results of therapy with these antibiotics are often disappointing . To evaluate whether the currently recommended antibiotic susceptibility tests for C . burnetii give misleading results because of continued division of uninfected cells, thereby resulting in the dilution of infected cells and, hence, a false picture of antibiotic efficacy, we blocked cell division during antibiotic susceptibility testing with cycloheximide . Using this new method, we found that the currently recommended antibiotics for the treatment of Q fever, doxycycline, pefloxacin, and rifampin, did not reduce the ratio of infected to noninfected cells (either L929 or P388D1) by 9 days postinfection . To test the hypothesis that this lack of antibacterial activity is due to antibiotic inactivation by the low pH of the phagolysosomes in which C . burnetii is found, we used alkalinizing lysosomotropic agents (chloroquine or amantadine) concurrently with doxycycline . This resulted in the sterilization of C . burnetii infection in P388D1 cells . This finding seems to confirm our suspicion that the acidic conditions of the phagolysosomes in which C . burnetii is located inhibit antibiotic activity . This inhibition can be reversed in vitro when lysosomotropic alkalinizing agents are used. Dtsch Tierarztl Wochenschr, 1990 Aug, 97(8), 307 - 13 {A review of the diagnostic possibilities of illegal drug administration in slaughtered animals and meat inspection}; Ellerbroek L; A review of possible residues of selected antibacterial substances, hormones, beta-agonists, thyreostatics and tranquillizers in meat is given in this paper . Showing their application mode and the few clinical effects and pathological findings, the collection of samples becomes very important . For each group of substances tissues or body-fluids are proposed as samples . With modern analytical detection methods residues in food of animal origin can be demonstrated at levels of micrograms/kg . The detection of the above mentioned substances could be supported by a well-aimed sampling and the illegal use can be diminished. Biopharm Drug Dispos, 1990 Aug-Sep, 11(6), 533 - 41 Pharmacokinetics of aditoprim in goats using a radioassay; Iqbal MP et al.; A simple, highly sensitive radioassay was developed for the activity of a newly discovered inhibitor of dihydrofolate reductase (DHFR), aditoprim . The procedure is based on the inhibition of binding of {3H}-methotrexate ({3H}MTX) with bacterial dihydrofolate reductase by the antifolate, aditoprim . The analytic sensitivity using this binding inhibition method was less than 5 ng in plasma . The procedure developed requires no extraction of the drug from the plasma . The variation of simultaneous duplicate determinations was 6.3 per cent, whereas the variability of plasma samples assayed on different days was less than 11 per cent . The assay developed was applied to study the pharmacokinetics of aditoprim in the goat . In comparison with trimethoprim (TMP), the new inhibitor of DHFR, aditoprim, had a longer half-life and a larger volume of distribution, suggesting enhanced and prolonged antibacterial activity of aditoprim over TMP. J Periodontol, 1990 Aug, 61(8), 536 - 41 Susceptibility of oral bacteria to phenoxyethanol and phenoxyethanol/chlorhexidine combinations; Wilson M et al.; A total of 57 bacterial strains (26 different species) which may be isolated from subgingival plaque were tested for their in vitro susceptibility to phenoxycthanol, a commonly-used antiseptic and preservative . Ninety-five percent of the strains, including those associated with chronic inflammatory periodontal disease, were susceptible to concentrations of phenoxyethanol used topically (2% w/v) . Phenoxyethanol at a concentration of 1% (w/v) was also found that to have a rapid bactericidal effect achieving a 99.9% kill in 5 minutes or less for species such as Bacterodides gingivalis, Fusobacterium nucleatum, Eikenella corrodens, and Wolinella recta . Addition of chlorhexidine to phenoxyethanol resulted in a mixture with increased antibacterial activity . For most bacterial strains, the presence of chlorhexidine resulted in at least a four-fold decrease in the concentration of pheoxyethanol required for inhibition of growth . These results imply that phenoxyethanol may be useful in the treatment of chronic inflammatory periodontal disease either by itself or in combination with chlorhexidine. Biochem Pharmacol, 1990 Aug 1, 40(3), 431 - 6 Relevance of ionic effects on norfloxacin uptake by Escherichia coli; Valisena S et al.; The uptake of the quinolone drug norfloxacin by Escherichia coli was investigated at initial rate kinetics at different pH and monovalent/divalent metal ion concentration . The results support a simple diffusion mechanism for quinolone incorporation into cells . The uptake process decreases under acidic conditions . The presence of Na+ or K+ ions does not affect the results to an appreciable extent, whereas divalent ions cause a dramatic decrease in drug incorporation . The antibacterial activity, evaluated under identical experimental conditions, shows a direct relationship with the uptake data . As a general explanation for the above results it is suggested that the ability of the drug to penetrate into cells is a function of its net charge . The molecule in the zwitterionic form exhibits maximum permeation properties, whereas the uptake is remarkably reduced when the drug bears a net charge as a result of ionization or complex formation with bivalent ions . These results allow further insight into the mechanism of quinolone access to the intracellular compartment. Vestn Khir Im I I Grek, 1990 Aug, 145(8), 20 - 2 {Lysosomal-cation test in the control of treatment of acute proctological diseases}; Minchin SIu et al.; An express evaluation of the functional state of neutrophil granulocytes by the indications of the lysosomal-cationic test are thought to be a necessary addition to routine clinico-laboratory methods of assessment of the wound process in patient with the suppurating epithelial coccygeal canal and acute paraproctitis . Use of cytochemical indices allow the antibacterial therapy to be optimized in patients with suppurating epithelial coccygeal canal and thus substantially decrease the amount of complications in the postoperative period. Ther Umsch, 1990 Aug, 47(8), 670 - 4 {Acne and its drug treatment}; Buchner SA; The most common disease of the pilosebaceous follicle is acne vulgaris . The primary detectable pathologic defect in acne is abnormal keratinization of the follicular epithelium, resulting in a retention hyperkeratosis . The primary lesion produced by this process, the comedo, ist the precursor of most other acne lesions . These include inflammatory papules, pustules and nodules . Treatment principles are directed against known pathogenic factors . The major topical modalities that are currently being used include tretinoin, benzoyl peroxide and topical antibiotics . Benzoyl peroxide is a powerful antibacterial agent . Topical erythromycin and clindamycin appear to have equivalent efficacy . A major treatment advance has been heralded by the use of oral 13-cis retinoic acid (isotretinoin) in the management of patients with severe nodulocystic acne, acne conglobata and acne fulminans . Isotretinoin is teratogenic and should not be given to women of childbearing age. Chem Pharm Bull (Tokyo), 1990 Aug, 38(8), 2271 - 3 Synthetic cephalosporins . VI . Synthesis and antibacterial activity of 7-{(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methyl) ethoxyiminoacetamido}- 3-(3-hydroxy-4-pyridon-1-yl)methyl-3-cephem-4-carboxylic acid and related compounds; Sakagami K et al.; Synthesis and antibacterial activity of 7-{(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methyl)ethoxyimin oacetamido}- 3-(3-hydroxy-4-pyridon-1-yl)-3-cephem-4-carboxylic acid (12) and its related compounds are described . Compound 12 exhibited excellent antibacterial activity against gram-negative bacteria, and its anti-pseudomonal activity was ten to fifteen times greater than that of ceftazidime. Chem Pharm Bull (Tokyo), 1990 Aug, 38(8), 2190 - 6 Synthesis of 7-thio-substituted 4-oxoquinoline-3-carboxylic acids with antibacterial activity; Nishimura Y et al.; A series of C-7 thio-substituted 1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared and tested for their antibacterial activity . Structure-activity relationships associated with the C-5 and C-7 substituents were discussed . Among the C-7 substituents including alkylthio, arylthio, heteroarylthio, and cyclic aminothio groups, a 2-aminoethylthio group was the best for enhancing in vitro antibacterial activity . The C-5 variants increased activity in the order OH less than F less than H less than NH2 . Of compounds prepared in this work, 5-amino-7-(2-aminoethyl)thio-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4 -oxo-quinoline-3-carboxylic acid (18) was the most active. J Antibiot (Tokyo), 1990 Aug, 43(8), 931 - 7 MM 47761 and MM 49721, glycopeptide antibiotics produced by a new strain of Amycolatopsis orientalis . Isolation, purification and structure determination; Box SJ et al.; Two glycopeptide antibiotics MM 47761 and MM 47921 have been isolated from Amycolatopsis orientalis NCIB 12608 . Fermentation conditions for their production, and methods for their isolation are described . The metabolites have been characterised by physio-chemical and biological properties and the structure determined by a combination of chemical degradation, COSY and NOE NMR studies . Both metabolites showed good antibacterial activity against Gram-positive organisms. Vet Rec, 1990 Jul 28, 127(4), 86 - 90 Bovine endometritis: comparative efficacy of alfaprostol and intrauterine therapies, and other factors influencing clinical success; Murray RD et al.; A comparative study of the treatment of 306 severe, moderate, or mild cases of bovine endometritis was carried out over two calving seasons . The cases were treated with alfaprostol, or an intrauterine antibacterial preparation, or with a combination of both therapies . There was no significant difference between the efficacies of these treatments, and a single injection of alfaprostol was effective in 74 per cent of the cases treated . The effectiveness of the treatments was related to the degree of self-cure of the endometritis after parturition, the luteal activity at the time of treatment, and farm management factors affecting the health and condition of the calving cows. Cas Lek Cesk, 1990 Jul 20, 129(29), 914 - 6 {Dual cephalosporins--a return of fixed combinations of antibiotics?}; Krcmery V Sr; The author submits information on the preparation and properties of new molecules of "tailored antibiotics"--dual cephalosporins . They are formed by esterification of cephalosporins of the third generation (so far only cephotaxim) with fleroxacine or another fluoroquinolone chemotherapeutic agent . The author discusses the aptness and advantage of this new approach to the innovation of the existing spectrum of antibacterial agents. J Biol Chem, 1990 Jul 5, 265(19), 11333 - 7 A potent antibacterial protein in royal jelly . Purification and determination of the primary structure of royalisin; Fujiwara S et al.; A new potent antibacterial protein, for which we propose the name royalisin, was found in royal jelly of the honeybee Apis mellifera L . and purified to homogeneity for the first time by acid extraction, gel filtration, and reverse-phase high pressure liquid chromatography . The primary structure of royalisin was determined to consist of 51 residues, with three intramolecular disulfide linkages, having a calculated molecular mass of 5523 Da . Royalisin is an amphipathic protein, with the C-terminal half of the molecule being rich in charged amino acids; and it showed extensive sequence homology to two other antibacterial proteins, sapecin from embryonic Sarcophaga peregrina cells and phormicins from Phormia terranovae larvae . Royalisin was found to have potent antibacterial activity against Gram-positive bacteria at low concentrations, but not against Gram-negative bacteria . Royalisin may be involved in a defense system active against bacterial invasion of the honeybee. Br J Clin Pharmacol, 1990 Jul, 30(1), 1 - 11 Screening for aminoglycoside auditory toxicity in the old; Cheung R et al.; 1 . We have investigated 22 patients receiving gentamicin, mean (s.d.) age 78 (6) years for auditory toxicity, using a standard audiometric technique in a sound-treated room (Study 1) . 2 . Use of a portable audiometer might allow a larger and more representative proportion of patients treated with aminoglycosides to be screened for ototoxicity . A method for detecting high frequency loss suitable for use in the ward was evaluated in 12 volunteers aged 27 (4) years (Study 2) . 3 . The error inherent in taking hearing at the start of treatment as a reference point was measured in 16 patients, aged 81 (8) years, prescribed non-ototoxic antibacterials (Study 3) . 4 . A significant (P = 0.05) reduction in hearing threshold was detected in Study 1, although psychometric tests revealed unchanged or improved ability to co-operate . This occurred only at 4000 Hz, the highest frequency used . The magnitude of this loss, mean 2.5 dB, was similar to that of the improvement in threshold detected (P = 0.0004) early in the course of treatment in Study 3 . Thus, underestimation of ototoxicity is likely . 5 . If a change of threshold of 10 dB or more is taken arbitrarily to represent a real change in hearing, then there was a significant excess of patients in Study 1 with losses at 4000 Hz only (P = 0.032) . The six with such losses at this frequency were older than the rest . However, there was a significant (P less than 0.02) positive correlation between log mean predose serum gentamicin concentration and age . Thus, it remains to be determined whether presbyacusis sensitizes those hair cells which it does not destroy to toxic damage . 6 . The cumulative dose of gentamicin (for a course of the duration given) was calculated according to published prescribing aids . There was no systematic reduction in the ratio of the dose recommended by a given aid to the dose prescribed in the six with hearing losses as defined above . 7 . In Study 2, thresholds obtained at 6000 Hz in the open ward were, on average, 0.9 dB higher than in the sound treated room, but the effect of venue did not reach statistical significance . In the morning thresholds were marginally, but significantly (P = 0.04), lower than in the afternoon . Precision, as measured by the standard deviation of replicate determination, was independent of test conditions . Using multiple (ten) threshold determinations appeared to improve resolution.(ABSTRACT TRUNCATED AT 400 WORDS) J Periodontol, 1990 Jul, 61(7), 393 - 8 A new degradable controlled release device for treatment of periodontal disease: in vitro release study; Steinberg D et al.; The substantivity of a drug in the periodontal pocket is an important factor determining its effect on the subgingival flora . Therefore, one of the predominant factors in the development of a sustained release delivery device is the ability to control the rate of release of the drug . Previous studies have demonstrated the advantages of the local sustained release of chlorhexidine from nondegradable devices in the treatment of periodontal diseases . The aim of this study was to develop a degradable sustained release device composed of a cross-linked protein containing chlorhexidine as the therapeutic agent . The in vitro release profile of chlorhexidine from the degradable films was altered by the amount of chlorhexidine incorporated into the film, by the cross-link density of the polymer, and by the chlorhexidine salt used . The chlorhexidine in the final pharmaceutical preparation did not lose its antibacterial activity as was shown in an in vitro antibacterial test . This work demonstrates that the release of chlorhexidine from a degradable delivery system and the degradation of the matrix can be controlled by variation in the formulation . This presents a new dental drug delivery system that can be used as an adjunct in the treatment of periodontal diseases in the future . These studies enable us to choose the pharmaceutical formulations for clinical trials to be conducted testing the efficacy of this treatment modality. J Antibiot (Tokyo), 1990 Jul, 43(7), 858 - 72 Amikacin analogs with a fluorinated amino acid side chain; Hoshi H et al.; The synthesis and biological activity of kanamycin A derivatives with an omega-amino-alpha-fluoroalkanoyl side chain on the 1-amino group are described . The fluorinated amino acids (4) for the side chain were prepared by fluorination of the alpha-hydroxy esters (2) with diethylaminosulfur trifluoride (DAST) with accompanying the Walden inversion . The reaction products varied with the amino protective groups employed, chain length of the alkanoic acids and the presence or absence of base . The fluorinated side chain was introduced to 1-free-NH2 kanamycin A (12) by the conventional active ester method and subsequent deblocking reactions afforded the desired final products (13-17) . Of the derivatives prepared, 1-N-{(S)-4-amino-2-fluorobutyryl}kanamycin A (2'''-deoxy-2'''-fluoroamikacin, 14) showed the best overall activity profile, nearly the same as that of amikacin . Preparation and antibacterial activity of several aminoglycoside antibiotics with the 1-N-(S)-4-amino-2-fluorobutyryl side chain are also discussed. Antibiot Khimioter, 1990 Jul, 35(7), 25 - 7 {Physiologic model of NY-198 pharmacokinetics using a new method of determining tissue/blood distribution coefficient}; Manuilov KK; A 10-compartment physiological model of pharmacokinetics of NY-198, a new pyridone carboxylic acid, with antibacterial activity is described . In its construction an original rapid method based on measuring xenobiotic concentration in one particular time point was used for determining the tissue/blood distribution coefficients . The results of simulating the antibiotic pharmacokinetic profiles by the Kd values known from the literature and the values estimated with the proposed method were compared. Stomatologiia (Mosk), 1990 Jul-Aug, (4), 29 - 33 {The pathogenetic aspects of the effect of hypoxia on the trigger mechanisms of suppurative-inflammatory complications in patients with combined maxillofacial and craniocerebral trauma}; Zuev VP et al.; Study of the relationship between the time course of secondary tissue hypoxia development and changes in the neutrophilic phagocytic activity, which was carried out in 65 patients with combined maxillofacial and craniocerebral injury, has revealed a detrimental effect of hypoxia on antibacterial defense factors of the body, this effect being conductive to development of pyoinflammatory complications; this should be borne in mind when planning treatment strategy. Hinyokika Kiyo, 1990 Jul, 36(7), 801 - 6 {Clinical studies on chronic prostatitis and prostatitis-like syndrome (4) . The kampo treatment for intractable prostatitis}; Ikeuchi T; Kampo treatment was attempted in cases of chronic nonbacterial prostatitis and prostatitis-like syndrome which was intractable or recurred when treated with western medicine . The clinical effects of Kampo treatment were excellent in 21.3% with an efficacy rate of 67.2% for the cases with chronic non-bacterial prostatitis, and excellent in 19.5% with an efficacy rate of 52.4% in the cases with prostatitis-like syndrome . When the clinical effects were compared with those of western therapy performed in the cases which had recurrence, Kampo treatment showed more excellent effects (p less than 0.1) for both types of disease, and the treatment with Chinese medicine was suggested useful . In a comparison of the effects between the cases given only Kampo treatment and those given both Kampo treatment and western treatment using anti-inflammatory agents, no difference was seen in the cases with the prostatitis-like syndrome, but in the cases with chronic non-bacterial prostatitis, the effects were better in the concomitant treatment group than in the group given only Kampo treatment (p less than 0.1) . The response to the Kampo treatment differed depending on the type of disease . Among the antibacterial agents used concomitantly in the cases of chronic non-bacterial prostatitis, new-quinolones showed better results than ST compounds or tetracyclines, but no statistically significant differences were seen among the drugs . Of the Kampo drugs used, Keisibukuryogan and Simotuto showed high clinical usefulness in both types of disease and there was no statistically significant difference among the other drugs . The incidence rate of side effects (Goji) due to Kampo treatment was 6.3% and was higher in patients administered Keisibukuryogan. Khirurgiia (Mosk), 1990 Jul, (7), 50 - 6 {Pathogenetic aspects of the treatment of diffuse suppurative peritonitis}; Lutsevich OE et al.; Experience with the treatment of 130 patients with generalized purulent peritonitis is analysed . The complex of therapeutic measures included intraoperative cleansing of abdominal cavity with ultrasound; postoperative prolonged laparoscopic cleansing with the use of rational antibacterial therapy and laser irradiation of the abdominal cavity . The cell immunity values in patients with peritonitis were studied and the principles of immunocorrective therapy substantiated . It is shown that detoxification measures are necessary in the treatment of this category of patients . A complex approach to the treatment of purulent peritonitis led to a decrease in mortality to 13.8%. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 510 - 6 Significance of tissue levels for prediction of antibiotic efficacy and determination of dosage; Carbon C; Determination of tissue levels is widely thought to provide useful information in the investigation of a new antibiotic, however this assumption is not fully justified . In this paper the following questions are covered . Firstly, the methodological problems encountered in the measurement of antibiotic levels in solid tissues and extravascular fluids are described . Secondly, the difficulties encountered in interpreting tissue concentrations are discussed, given the heterogeneity of distribution of drugs, potential intracellular penetration, binding to tissue proteins and local factors reducing antibacterial activity . Thirdly, the respective importance of animal and human data on tissue levels for prediction of efficacy is analysed . In some animal models it is possible to study the conditions affecting antibacterial activity and to obtain data relevant to the clinical situation . However, the inoculum effect, the metabolism of bacteria, the mechanism of the bactericidal action of drugs and the type of infected tissue are important factors to be taken into account . In humans, data obtained from infected tissue is sparse and contributes little to knowledge . Knowledge of tissue levels may be important for establishing whether data obtained in animals can be applied to humans or not . Fourthly, the importance of tissue levels in determining antibiotic dosages is evaluated . In humans, tissue levels are of limited value in the determination of unitary dose and dosage intervals in relation to the clinical response . Trough serum levels of free drug, half-life at the beta-phase and rate of in vitro killing are the most important parameters to be considered . Their relative importance depends mainly on the mode of action of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 479 - 87 Correlation between pharmacokinetics, pharmacodynamics and efficacy of antibacterial agents in animal models; Dalhoff A et al.; On the basis of a review of published literature it is demonstrated that pharmacokinetic parameters of antibacterial agents correlate well with therapeutic efficacy in animal models, provided pharmacodynamic parameters are taken into account . The time that serum levels exceed the MIC is the most significant parameter determining efficacy of beta-lactams, whereas the efficacy of aminoglycosides is dependent on serum concentrations and the area under the curve . The efficacy of quinolones tends to be correlated to the doses administered or drug levels achieved . However, specific pharmacodynamic properties contribute significantly to the therapeutic efficacy of a few quinolones only whereas other quinolones lack these specific pharmacodynamic attributes . Thus, the correlation of pharmacokinetic parameters with therapeutic efficacy provides important basic concepts for the design of preclinical and clinical studies in the course of which additional pharmacodynamic properties will become apparent. Transpl Int, 1990 Jul, 3(2), 113 - 5 Disseminated tuberculosis after renal transplantation . A report of two cases; Schorn TF et al.; Disseminated mycobacterial infections occurred in two female renal graft recipients late after transplantation . In the first patient, initially presenting with fever, diagnosis was made at autopsy . Temporary defervescence following antibiotic therapy with ofloxacin possibly contributed to the fatal diagnostic delay . In the second case, body temperature was normal throughout the protracted course of the patient's illness . Her presenting symptom was rapidly increasing ascites, attributed initially to chronic liver disease . These cases demonstrate that tuberculosis remains a serious complication after renal transplantation, in particular due to its sometimes atypical clinical manifestations . Response to antibacterial therapy has to be critically evaluated in order to avoid fatal diagnostic delay. J Antibiot (Tokyo), 1990 Jul, 43(7), 847 - 57 Synthesis and antibacterial activity of C-2 carboxyethenylthio-carbapenem derivatives; Basker MJ et al.; A number of C-2 carboxyethenylthio-carbapenem derivatives possessing either the (5R,6R,8S)- or the (5R,6S,8R)-stereochemistries have been prepared from the olivanic acids MM 22382 (1) and MM 22383 (4), respectively . Their in vitro antibacterial activities and stabilities to human kidney homogenate are superior to those of the parent compounds, particularly in the latter series. Br J Ophthalmol, 1990 Jul, 74(7), 433 - 6 Endogenous Nocardia asteroides endophthalmitis in a patient with systemic lupus erythematosus; Ishibashi Y et al.; We report a case of endogenous Nocardia endophthalmitis in a patient with systemic lupus erythematosus (SLE) . He developed a parafoveal lesion in the right fundus while on systemic corticosteroid and antibiotic treatment . Initially we suspected a fungal origin and treated him with antifungal drugs . The intraocular disease progressed without improvement and advanced to the vitreous cavity . Nocardia asteroides was found in a specimen obtained at pars plana vitrectomy and was also cultured from the same specimen . The intraocular infection was controlled by antibacterial drugs, though the visual acuity of the right eye was reduced to only light perception owing to heavy vitreous opacity and secondary cataract . This case is the first report of endogenous Nocardia endophthalmitis in Japan and also the first case of this disease reported from outside the United States of America. Med Clin North Am, 1990 Jul, 74(4), 1025 - 37 Medical and surgical complications of renal transplantation: diagnosis and management; Yoshimura N et al.; Renal transplantation is a common modality of therapy in end-stage renal failure, but it has the potential of developing many complications, both surgical and medical in nature . In transplantation surgery, more than in any other type of surgery, prevention of these complications is essential . This includes attention to many details, including optimum organ salvage, preservation, implantation, and postoperative care . Although infection has decreased in frequency and severity with the advent of antiviral and antibacterial agents, prevention, early diagnosis, and suitable treatment with appropriate antibiotic(s) will be necessary to obtain desirable results and to reduce morbidity and mortality . It should be stressed that although careful attention to the patients and adjustment of the immunosuppressive regimen may mitigate much of the gastrointestinal, hematologic, and osteogenic complications, high incidence of cancer of the skin and mucous membrane continues. Pediatr Rev, 1990 Jul, 12(1), 15 - 21 Peptic ulcer disease in children; Gryboski JD; Chronic gastroduodenal ulceration is the end product of an imbalance between acid levels, peptic hostile factors, and mucosal defenses . This condition differs significantly from stress ulceration, in which the primary factor is decreased mucosal blood flow, and from nonsteroidal anti-inflammatory drug-induced injury, in which there is local vascular injury and inhibition of prostaglandin synthesis . The identification of H pylori as a cause of chronic gastritis, duodenitis, and peptic ulcer is required for specific antibacterial therapy. J Biochem (Tokyo), 1990 Jul, 108(1), 128 - 32 Mode of action of sapecin, a novel antibacterial protein of Sarcophaga peregrina (flesh fly); Matsuyama K et al.; Sapecin is an antibacterial protein purified from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina {Matsuyama, K . & Natori, S . (1988) J . Biol . Chem . 236, 17112-17116} . As this protein inhibited the growth of Gram-positive bacteria better than that of Gram-negative bacteria, we studied its mode of action with special reference to its effects on S . aureus and Escherichia coli . Results showed that sapecin had high affinity for cardiolipin, which is a major phospholipid of S . aureus . Moreover, a mutant of E . coli with a defect in cardiolipin synthesis was more resistant to sapecin than wild type E . coli, suggesting that cardiolipin is a target for sapecin . Lipopolysaccharide of E . coli was also found to be a barrier for the antibacterial activity of sapecin. J Med Chem, 1990 Jul, 33(7), 2012 - 5 Synthesis and antibacterial activity of thiazolo-, oxazolo-, and imidazolo{3,2-a}{1,8}naphthyridinecarboxylic acids; Kondo H et al.; It is known that thiazolo{3,2-a}{1,8}naphthyridine derivatives (3a) exhibit good antibacterial activity . Accordingly, several analogues of 3a, viz . oxazolo- and imidazolo{3,2-a}{1,8}naphthyridine derivatives 3b and 3c, were synthesized and evaluated for antibacterial activity in vitro and for inhibitory activity against DNA gyrase of Escherichia coli K-12 C600 . Compound 3a exhibited antibacterial activity comparable to that of ofloxacin and enoxacin against Gram-positive and Gram-negative bacteria and displayed antibacterial activity superior to that of 3b and 3c . The antibacterial activities of 3b and 3c decreased in that order . DNA gyrase inhibitory activities of 3a-c in E . coli K-12 C600 paralleled their in vitro antibacterial activity . It was found that enhancement of the DNA gyrase inhibitory activity of 3a was dependent on a certain feature of the sulfur atom of the thiazole ring. Antibiot Khimioter, 1990 Jul, 35(7), 44 - 7 {Optimal control of the microflora environment in suppurative foci}; Menshikov DD et al.; The informative capacity of various statistic parameters characterizing the ecology of pathogens of purulent processes was studied . Many-years' results of the routine bacteriological tests of the materials from purulent wounds in patients from surgical, traumatological and burn departments served as the study subjects . The frequency, persistence and contamination capacity of the pathogens were investigated . Data on the changes in the frequency parameter with respect to the main pathogens of wound infections in various contingents of patients were collected . In relation to the observation period and contingent of the patients, various microorganisms were found to be permanent, supplementary and casual . The use of the ecological parameters was shown to provide integrated information on the etiological role of the pathogens in the development of purulent processes . The information characterized the microbial properties which should be considered in planning the use of antibacterial drugs and estimating the efficacy of the epidemiological control. In Vivo, 1990 Jul-Aug, 4(4), 221 - 3 Lignified materials as potential medicinal resources . II . Prevention of pathogenic bacterial infections in mice; Oh-Hara T et al.; Antibacterial activity was demonstrated when ddY mice were intraperitoneally infected with E . coli or P . aeruginosa two days after a single ip-injection of a hot-water or alkaline extract obtained from lignified materials, such as chips of slash pine, Douglas fir, tallow wood, and two shelf fungi . Lignified material is a promising medicinal resource for the prevention and/or treatment of pathogenic microbial infection. Quintessence Int, 1990 Jul, 21(7), 589 - 98 Apexification: review of the literature; Morse DR et al.; Five methods for the treatment of teeth with an incompletely formed apex (open apex) and a necrotic pulp are discussed . The methods discussed include the use of (1) a customized cone (blunt-end, rolled cone); (2) a short-fill technique; (3) periapical surgery (with or without a retrograde seal); (4) apexification (apical closure induction); and (5) one-visit apexification . The apexification techniques, which use various formulations of calcium hydroxide to induce closure, are stressed . Based on the review of the literature and clinical experience of the authors, it was concluded that successful treatment of an immature pulpless tooth can partly result from the antibacterial and calcification-inducing action of calcium hydroxide. Mol Pharmacol, 1990 Jul, 38(1), 20 - 5 Inhibition of human immunodeficiency virus-1 reverse transcriptase activity by rubromycins: competitive interaction at the template.primer site; Goldman ME et al.; Rubromycins, a class of quinone antibacterials, were discovered to selectively inhibit human immunodeficiency virus-1 (HIV-1) RNA-directed DNA polymerase (reverse transcriptase) (RT) activity more potently than cellular DNA polymerase alpha . beta- and gamma-rubromycin each inhibited equipotently HIV-1 RT and avian myeloblastosis virus RT, in a concentration-dependent manner, and were significantly weaker as inhibitors of calf thymus DNA polymerase alpha . These agents inhibited HIV-1 RT reversibly, were competitive with respect to template.primer, and were noncompetitive with respect to TTP . Dixon analyses yielded HIV RT Ki values of 0.27 +/- 0.014 and 0.13 +/- 0.012 microM for beta- and gamma-rubromycin, respectively . Similarly, using DNA polymerase alpha, the Ki values were 25.1 +/- 4.3 and 3.9 +/- 0.6 microM for beta- and gamma-rubromycin, respectively . Because these agents were toxic to noninfected human T lymphoid cells using concentrations at or above 6 microM, HIV-1 infectivity studies were carried out at 0.8-6 microM . At these concentrations, which are below the range expected to provide protection, no significant antiviral activity was observed . Although beta- and gamma-rubromycins did not possess sufficient HIV RT inhibitory potency or selectivity versus mammalian DNA polymerase to demonstrate antiviral activities, these studies support the hypothesis that specific molecules containing quinone functional groups can selectively inhibit viral polymerase activities over cellular polymerase activities . In addition, these studies suggest that rubromycins may be lead structures for the development of more potent and selective agents. Vet Rec, 1990 Jun 30, 126(26), 635 - 7 Cephalexin in ponies: a preliminary investigation; Lees P et al.; The administration of a single dose of the antibacterial agent cephalexin intramuscularly to six ponies at a dose rate of 7 mg/kg was well tolerated . No reactions at the injection site were apparent . It was absorbed rapidly and reached a mean peak plasma concentration of 6.77 micrograms/ml after a mean of 1.41 hours; plasma concentrations above 2.0 and 0.5 micrograms/ml were maintained for 3.8 and 9.8 hours, respectively. J Biol Chem, 1990 Jun 25, 265(18), 10438 - 42 A synthetic 13-residue peptide corresponding to the hydrophobic region of bovine seminalplasmin has antibacterial activity and also causes lysis of red blood cells; Sitaram N et al.; Seminalplasmin (SPLN), a 47-residue peptide present in bovine seminal plasma, is one of the few proteins isolated from mammalian sources having potent antibacterial activity . SPLN also interacts with sperm acrosomal and plasma membranes . On the basis of analysis of the primary structure of SPLN with respect to its relative hydrophobicity and hydrophilicity, a region comprising of 13-amino acids, Pro-Lys-Leu-Leu-Glu-Thr-Phe-Leu-Ser-Lys-Trp-Ile-Gly, has been delineated . It is demonstrated that a synthetic peptide corresponding to this 13-residue region inhibits growth of Escherichia coli like SPLN and also has the ability to lyse red blood cells. Ned Tijdschr Geneeskd, 1990 Jun 23, 134(25), 1227 - 9 {Inefficacy of oral contraception during use of minocycline}; de Groot AC et al.; A healthy woman aged 21 years who used the oral contraceptive Trigynon became pregnant while being treated with Minocin (minocycline; 100 mg per day) for acne conglobata . While the risk of use of antibiotics such as this one reducing the efficacy of oral contraceptives is small, patients should nevertheless be informed that the risk existsPIP: A 21-year old woman using an oral contraceptive, the combination preparation Trigynon containing levonorgestrel (LNG) and ethinyl estradiol (EE), since June 1987 had experienced pain in the groin . In September 1988 she had a single occurrence of bleeding, a sign of lessened effectiveness of the OC . She was treated with 50 mg of minocycline/day as of April 1989, and for inguinal acne conglobata with locally applied clindamycine (10 mg/ml of clindamycine hydrochloride lotion) . She switched to another OC, and the next month timely, normal menstruation ensued . A few days later the dose of minocycline was raised to 100 mg/day . Subsequently she had a regular breakthrough bleeding followed by a missed cycle and a positive pregnancy test . There have been several recent reports about the interaction between antibiotics and OCs (breakthrough bleeding and contraceptive failure) . Rifampicin and griseofulvin are known to reduce the activity of OCs via induction of liver enzymes . Between 1968-84 there was a total of 62 failures of OCs (15 using OCs with 50 mcg of EE) reported in the UK . The suspected cause was the combined use with antibiotics (70% penicillin and tetracycline) . In the Netherlands 6 cases of possible interactions were reported during 1980-86: 2 cases caused by nitrofurantoin and/or trimethoprim, and 1 case by sulfamethoxazol with trimethoprim . The interference of minocycline with the intestinal flora can occur as 34% of it is excreted in feces, and its antibacterial spectrum corresponds to that of tetracycline hydrochloride (reduction of beta-glucuronidase in the feces) . The failure of Trigynon cannot be irrefutable ascribed to minocycline as unintended pregnancy also occurs while using OCs without antibiotics . Clindamycine could have also influenced the intestinal flora percutaneously . Hosp Pract (Off Ed), 1990 Jun 15, 25(6), 181 - 94 Antibacterial therapy: problems and promises, Part II; Neu HC; Numerous antibacterial agents recently or soon to be available are reviewed: new quinolones, macrolides, aminoglycosides, glycopeptides, and lipopeptides . Overall, these agents do much to improve antibacterial activity against problem organisms, overcome resistance, and reduce toxicity and frequency of administration . Many are orally administered and will shorten hospital stays. Antibiot Khimioter, 1990 Jun, 35(6), 34 - 7 {Increasing the effectiveness of ampicillin in combination with lysozyme}; Shcherbakova EG et al.; The effect of lysozyme (2 mg/kg) on pharmacokinetics of ampicillin (60 mg/kg) and the lymph nodes was studied in a model of experimental diffuse peritonitis in 52 dogs . The drugs were administered intramuscularly in single doses simultaneously with simulation of the pathological process . Under such conditions, lysozyme promoted an increase in the ampicillin concentration in the lymphatic system, blood and tissues and prolonged the antibacterial activity to 18 hours of the experiment . This resulted in retarding lympho- and hematogenic dissemination of the infection from the primary focus and lowered the infectious and toxic affection of the regional lymph nodes, thus securing their barrier and immunological function . With lysozyme used in combination with the antibiotic the immunomorphological zones of the lymph nodes appeared to be preserved and the volumetric proportion of macrophages increased . Then the volumetric proportion of the blast cells and the frequency of macrophagal and lymphocytic interactions also increased . The most pronounced cell interactions were observed in the distal (tracheobronchial) lymph nodes whose functions before the infection generalization were mainly immunological. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1160 - 4 Pharmacokinetics of cephem antibiotics in exudate of pelvic retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy; Ito K et al.; Many cephalosporin antibiotics have recently been invented and attempts have been made to use them clinically . The choice of which of these drugs should be used has been difficult in gynecology . The efficacies of these drugs depend on their antibacterial spectra, potencies, and concentrations in tissues . This study was designed to investigate the pharmacokinetics of various cephem antibiotics in the exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy . These cephem antibiotics were cefoxitin, cefotiam, cefotetan, cefpiramide, cefminox, cefotaxime, ceftizoxime, cefoperazone, cefmenoxime, cefbuperazone, ceftazidime, cefpimizole, flomoxef, and cefuzonam . The maximum concentrations after administration of a 1-g dose in the exudate of the pelvic retroperitoneal space were 37.9 micrograms/ml with cefminox, 30.3 micrograms/ml with cefpimizole, 21.6 micrograms/ml with flomoxef, 21.5 micrograms/ml with ceftazidime, and 17.6 micrograms/ml with cefbuperazone, which were relatively high . When selecting antibiotics for prophylactic use against infections in the retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy, on the basis of drug transfer, flomoxef, cefminox, cefbuperazone, ceftazidime, and cefpimizole were considered to be the drugs of first choice at a dose of 1 g. Analyst, 1990 Jun, 115(6), 797 - 9 Determination of antibacterial agents in microbiological cultures by high-performance liquid chromatography; Taylor RB et al.; A general high-performance liquid chromatographic (HPLC) procedure is described which allows the assay of several antibacterial drugs in combination in a matrix of bacterial cell cultures . The drugs assayed were dibromopropamidine, trimethoprim, sulphadiazine and sulphamerazine . It is also shown that p-aminobenzoic acid, which is an essential metabolite of many micro-organisms, does not interfere and can itself be quantified . The method uses solid-phase extraction on a cyclohexyl-bonded silica with subsequent separation of the analytes by reversed-phase HPLC . Tetrabutylammonium is used in order to reduce the retention of trimethoprim and dibromopropamidine and quantification is by ultraviolet detection at 254 nm . The analytical characteristics of the proposed method are shown for certain drug combinations. J Chemother, 1990 Jun, 2(3), 167 - 70 In-vitro sensitivity of amoxicillin/clavulanic acid (Augmentin) to isolated beta-lactamases and in-vitro antibacterial activity; Esposito S et al.; The in vitro sensitivity of amoxicillin alone and combined with clavulanic acid (ratio 4:1) as been studied by a spectrophotometric method utilizing crude extract of the following enzymes: TEM1, TEM2, SHV1, SHV2, TLE1, HMS1, LXA, P99, ENT208 . The in-vitro antibacterial activity of ampicillin, amoxicillin alone and associated with clavulanic acid was also determined by an agar dilution method . Clavulanate protects amoxicillin from the hydrolytic activity of plasmid mediated beta-lactamase, conferring a stability on the beta-lactam comparable with that of cefotaxime . The protection of amoxicillin by means of clavulanic acid reduces the minimal concentration of antibiotic necessary to inhibit most bacterial species and allows bacteria to remain sensitive to the drug which might otherwise be resistant. J Antibiot (Tokyo), 1990 Jun, 43(6), 594 - 600 A54145, a new lipopeptide antibiotic complex: isolation and characterization; Fukuda DS et al.; A54145 is a complex of acidic lipopeptide antibiotics which are produced by Streptomyces fradiae and are active against Gram-positive bacteria . The A54145 complex was isolated by adsorption on Diaion HP-20 nonfunctionalized macroreticular resin and/or ion exchange on Amberlite IRA-68 anion exchange resin . Antibacterial factors A, A1, B, B1, C, D, E, and F were obtained in purified form by repeated preparative reverse phase HPLC on C8 and/or C18 bonded-phase supports . The molecular formulae of the factors are C72H109N17O27 (factors A and A1), C73H111N17O27 (factors B, B1, C, and D), C74H113N17O27 (factor E), and C71H107N17O27 (factor F) . The identities of the acyl side chains were established as 8-methylnonanoyl (factors F, A, and B1), n-decanoyl (factors A1 and B), and 8-methyldecanoyl (factors C, D, and E). J Pediatr Surg, 1990 Jun, 25(6), 669 - 71 The role of videourodynamic studies in diagnosis and treatment of vesicoureteral reflux; Scholtmeijer RJ et al.; From January 1986 to January 1988, 63 children with 95 refluxing ureters have been studied in a prospective study with videourodynamic examination . All children with reflux grades I, II, and III received antibacterial treatment . Surgical treatment was adopted for reflux grades IV and V, provided detrusor instability had been excluded . However, if there was detrusor instability, anticholinergic drugs and antibacterial treatment were given in all grades of reflux and videourodynamic examination was repeated after 3 to 6 months and after 12 months of therapy . Bilateral reflux was found in 22 of 38 patients with a stable bladder, and reimplantation was performed in 11 patients with 18 refluxing ureters . In 25 children with 35 refluxing ureters of various grades of reflux, detrusor instability was found and unilateral reflux was noted more frequently than bilateral reflux . Surgery was necessary for only five children, because in the majority of the patients detrusor instability and reflux could be treated by anticholinergic drugs and antibacterial treatment . For the decision as to which treatment should be given in vesicoureteral reflux, a videourodynamic study is mandatory. J Med Chem, 1990 Jun, 33(6), 1645 - 56 Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency; Miyamoto T et al.; A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4(1H)-oxoquinoline-3-carboxylic acids (10-36) were prepared; the C-5 substituent in these compounds comprised halo, hydroxy, mercapto, and amino groups and the C-7 functional group included variously substituted piperazines . In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents . A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with lack of adverse drug interactions . Compound 36k {named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid} was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent. Semin Respir Infect, 1990 Jun, 5(2), 111 - 22 Invasive pulmonary aspergillosis in patients with neoplastic diseases; Walsh TJ; Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in granulocytopenic patients . The purpose of this article is to review the current understanding of the microbiology, hospital epidemiology, clinical manifestations, diagnosis, prevention, and treatment of invasive pulmonary aspergillosis . Aspergillus conidia (spores) are inhaled from environmental sources into the paranasal sinuses and lower respiratory tract . Persistent fever, pulmonary infiltrates, and pleuritic pain in granulocytopenic patients receiving antibacterial antibiotics is a common manifestation of invasive pulmonary aspergillosis . Computerized tomographic scans of the chest often reveal characteristic peripheral nodules that also may progress to characteristic cavitary lesions . Hemoptysis may develop due either to hemorrhagic infarction during granulocytopenia or to the rupture of mycotic aneurysms during recovery from granulocytopenia . Aspergillus organisms may extend locally from the lung to involve other thoracic structures, including the heart and chest wall, and may disseminate to extrapulmonary sites, such as the brain, where focal neurological deficits ensue . Early diagnosis of invasive pulmonary aspergillosis may be difficult . Isolation of Aspergillus organisms from respiratory secretions of a persistently febrile granulocytopenic patient is usually indicative of invasive pulmonary aspergillosis and should not be dismissed as a contaminant or saprophyte . Amphotericin B is the treatment of choice; however, high dosages (1.0 to 1.5 mg/kg/day) are often necessary . Aspergillosis may develop in granulocytopenic patients who are already receiving empirical amphotericin B in lower doses (0.5 to 0.6 mg/kg/day) . It is hoped that further investigation directed toward an understanding of pathogenesis, improving diagnostic methodology, and developing new therapeutic and preventive strategies will improve the outcome of this life-threatening infection. Rev Fr Endod, 1990 Jun, 9(2), 31 - 9 {In vitro evaluation of the antibacterial activity of endodontic drugs}; Lardinois ML et al.; The antibacterial activity of camphorated phenol, iodine-potassium iodide, aqueous 2% glutaraldehyde, Rockles 4, Cresophene and Terra-Cortril has been tested in vitro against 21 species of bacteria . After 2 minutes of contact between medication and bacteria, Rockles 4, Cresophene, IKI and camphorated phenol inhibited completely all the tested bacteria . Terra-Cortril and aqueous glutaraldehyde 2% even pures were ineffective against all the bacteria species . Only Cresophene remained effective against 4 bacteria species when diluated 100 times. Chem Pharm Bull (Tokyo), 1990 Jun, 38(6), 1672 - 4 New fatty monoesters of erythromycin A; Philippe M et al.; New fatty polyenic (linoleic, linolenic, arachidonic, linoelaidic) mono esters of erythromycin A have been synthesized by using various reagents such as acyl chloride, carboxylic acid anhydride, and mixed carbonic anhydride . These different ways of activating the fatty acid allowed a regioselectivity of esterification at position 2' of the desosamine ring or position 4" of the cladinose ring of erythromycin A . The in vitro antibacterial properties of these new esters against members of the resident flora of the human skin were determined and compared with those of erythromycin A . The number and the stereochemistry of the double bonds seem to play a crucial role in the expression of the in vitro antibacterial activity. Eur Respir J, 1990 Jun, 3(6), 725 - 7 The airways effects of inhaled chlorbutol in asthmatic subjects; Windom H et al.; Chlorbutol is an antibacterial and antifungal agent incorporated in terbutaline (Bricanyl) nebulizer solution . Ten stable atopic asthmatic subjects undertook bronchial challenge testing, according to a double-blind protocol . Patients inhaled doubling concentrations of either methacholine (0.13-4.0 mg.ml-1) or chlorbutol (0.16-5.0 mg.ml-1) for 2 min until the forced expiratory volume in one second (FEV1) had fallen by 20% from baseline . If this had not occurred following the administration of the final concentration, then this highest concentration was repeated for 4 min . The nine subjects completing the study had a geometric mean provocation concentration producing a 20% fall from baseline FEV1 (PC20) methacholine of 0.16 mg.ml-1 (range less than 0.125-0.475 mg.ml-1) . After inhalation of 2.5 mg.ml-1 chlorbutol one subject experienced a fall in FEV1 greater than 20% . In the remaining eight subjects, inhalation of chlorbutol did not affect airway calibre . We conclude that chlorbutol, in the concentration present in Bricanyl nebulizer solution, has no clinically significant effect on airway calibre. Khirurgiia (Mosk), 1990 Jun, (6), 59 - 63 {Quantitative evaluation of humoral and cellular factors of antibacterial protection in patients with postoperative hernia complicated by suppurative process}; Usenov DA et al.; The article presents material on the study of the dynamics of humoral factors of the organism's antibacterial protection in correlation with factors of cellular immunity in 78 patients with postoperative ventral hernias complicated by a pyoinflammatory process . Factors of cellular immunity were studied in 33 patients, humoral factors of the organisms' antibacterial protection, in 45 patients . A distinct relation of the character of disorders of these factors to the type of the operation was revealed and their prognostic significance for clinical medicine was determined. Hell Period Stomat Gnathopathoprosopike Cheir, 1990 Jun, 5(2), 53 - 8 {The use of prophylactic antibiotics in oral and maxillofacial surgery}; Antoniadis K et al.; Cultures of postoperative wounds after head and neck surgery reveal a variety of oropharyngeal anaerobic and aerobic flora, aerobic gram negative rods and fungi . Control clinical trials have shown that preoperative antibacterial prophylaxis reduces the incidence of postoperative wound infections . When an antibiotic is used prophylactically, it must be active against the micro-organisms known to cause the infection which the patient is supposed to be protected from . Antibacterial prophylaxis should begin just before the operation beginning, earlier is unnecessary and beginning later is less effective . It is indicated for a variety of surgical procedures that high risk of wound sepsis, superinfection and the emergence of resistance has not been shown to occur if antibacterial agents are used only "perioperatively". Actual Odontostomatol (Paris), 1990 Jun, 44(170), 237 - 56 {Periodontal diseases and antibacterial drug treatment}; Huynh C et al.; Recent data concerning the bacteriology of periodontal diseases justify the use of antibacterial drugs . In advanced or resistant forms of the disease, the standard treatments are in fact insufficient . The antibacterial agents advocated include systemic antibiotics and local antiseptics . These products may be used separately or in combination . But, this antibacterial treatment remains a complementary option and cannot replace conventional treatments. Proc Natl Acad Sci U S A, 1990 Jun, 87(12), 4761 - 5 All-D amino acid-containing channel-forming antibiotic peptides; Wade D et al.; The D enantiomers of three naturally occurring antibiotics--cecropin A, magainin 2 amide, and melittin--were synthesized . In addition, the D enantiomers of two synthetic chimeric cecropin-melittin hybrid peptides were prepared . Each D isomer was shown by circular dichroism to be a mirror image of the corresponding L isomer in several solvent mixtures . In 20% hexafluoro-2-propanol the peptides contained 43-75% alpha-helix . The all-D peptides were resistant to enzymatic degradation . The peptides produced single-channel conductances in planar lipid bilayers, and the D and L enantiomers caused equivalent amounts of electrical conductivity . All of the peptides were potent antibacterial agents against representative Gram-negative and Gram-positive species . The D and L enantiomers of each peptide pair were equally active, within experimental error . Sheep erythrocytes were lysed by both D- and L-melittin but not by either isomer of cecropin A, magainin 2 amide, or the hybrids cecropin A-(1-13)-melittin-(1-13)-NH2 or cecropin A-(1-8)-melittin-(1-18)-NH2 . The infectivity of the bloodstream form of the malaria parasite Plasmodium falciparum was also inhibited by the D and L hybrids . It is suggested that the mode of action of these peptides on the membranes of bacteria, erythrocytes, plasmodia, and artificial lipid bilayers may be similar and involves the formation of ion-channel pores spanning the membranes, but without specific interaction with chiral receptors or enzymes. Minerva Chir, 1990 May 15, 45(9), 677 - 81 {The use of a topical antibacterial agent (silver sulfadiazine) on soft-tissue wounds}; Bocchiotti G et al.; Reducing the quantitative level of bacterial contamination in an open, acute or chronic, soft tissue wound below the critical level of 10(5) bacteria per gram of viable tissue is essential to delayed primary closure . First step in the management of the contaminated or infected wound is accurate local debridement, preferably with pulsating jet irrigation . Topical antibacterial agents, specifically silver sulfadiazine cream, are then usefully employed to reduce the bacterial count . Contrary to systemic antibiotics, these agents penetrate adequately into the open, granulating wound with a direct bacteriostatic or bactericidal action on a wide spectrum of gram positive and negative organisms, without the effect of local tissue injury typical of topical antiseptics . The use of topical antibacterials, traditionally confined to the treatment of the burn wound, the open "difficult" wound for excellence where control of local infection is first priority, provides a rapid local reduction of the bacterial level and paves the way to the final goal of primary delayed closure of the wound, either direct or with the use of grafts or local, distant, or free flaps. Hosp Pract (Off Ed), 1990 May 15, 25(5), 63 - 74, 77-8 Antibacterial therapy: problems and promises, Part I; Neu HC; Agents approved for clinical use in the past five years and others most likely to be available in the near future are evaluated in this two-part review . This installment is devoted entirely to the beta-lactam antibiotics--penicillins, cephalosporins, monobactams, and carbapenems . There are more similarities than differences among them, but the variations give each agent a range of appropriate uses. Cesk Farm, 1990 May, 39(3), 109 - 12 {Preparation of derivatives of 3-(3,4-dimethoxyphenyl)propanic acid and a study of its biological activity}; Novacek L et al.; From 3-(3,4-dimethoxyphenyl)propenic acid chloride and substituted amines and hydrazides, the appropriate amides and hydrazides (Table 1) were synthesized at 60-80 degrees C in the medium of benzene or toluene . The reaction of this chloride with benzaldehyde hydrazone at 70-80 degrees C yielded N,N'-bis{3-(3,4-dimethoxyphenyl)propenoyl}hydrazine (VIII) . At ambient temperature the benzylidene hydrazide of 3-(3,4-dimethoxyphenyl)propenic acid (VII) and a small amount of compound VIII were isolated . In the reaction of 3-(3,4-dimethoxyphenyl)propenic acid chloride with benzylidene hydrazide (VII) at 70-80 degrees C, compound VIII was obtained (Scheme 1) . Compounds I, VII, VIII and IX possessed higher indices of increase in fortnight tests of the first degree in the roosters of meat hybrides compared to the negative control, but the indices of conversion were unfavourable . The compounds did not reach the efficacy of the avoparcin standard . Derivatives II and VI possessed 67.5 and 63.5%, respectively, of anthelmintic activity of levamisol against Nippostrongylus brasiliensis . The prepared compounds were not antibacterially effective and they were not mutagenic in the tests following the method of Ames, either. Klin Med (Mosk), 1990 May, 68(5), 77 - 81 {The first experience with using autologous macrophages in the complex treatment of patients with destructive pulmonary tuberculosis}; Chuchalin AG et al.; To correct local immunity, a suspension of autologous macrophages (AM) produced by culturing peripheral blood monocytes has been introduced in combined treatment of 15 patients with infiltrative, local disseminated, cavernous, fibrocavernous tuberculosis and tuberculoma (8, 1, 1, 4 and 1 case, respectively) . AM treatment was added to the standard antibacterial and pathogenetic therapy . AM were introduced into the subsegmental bronchus at fibrobronchoscopy via a catheter inserted into the cavern-draining bronchus . The trial showed AM-promoted resolution of pulmonary tissue infiltrates and more intensive repair processes . The best results were obtained in 11 new-onset cases of pulmonary tuberculosis. Jpn J Antibiot, 1990 May, 43(5), 890 - 4 {Clinical study on norfloxacin in children}; Okada K et al.; Norfloxacin (NFLX, AM-715), a new synthetic antibacterial agent, was administered to 18 child patients with infectious diseases . The patients included 5 boys and 13 girls from 3 to 14 years of ages . They were given orally dosage ranging 5.2-17.9 mg/kg/day for 4 to 14 days . Clinical efficacies were excellent in 1 case, good in 16 cases, unknown in 1 case, hence the total efficacy rate was determined to be 100% . There were no cases which showed side effects of the drug and no abnormal laboratory test values were observed during the treatment. Arzneimittelforschung, 1990 May, 40(5), 614 - 7 Evaluation of ibuprofen dimethyl aminoethanol octyl bromide and related active metabolites in biological samples; Marzo A et al.; AF 150 is ibuprofen dimethyl aminoethanol octyl bromide, endowed with antibacterial and antiinflammatory activities . An indirect HPLC analytical method for AF 150 with UV detection, to be used for pharmacokinetic studies, has been validated in terms of linearity, reproducibility, specificity and sensitivity . Using this method the bioavailability of AF 150 and its active metabolite ibuprofen was investigated following parenteral administration and topical application. Pharmacol Toxicol, 1990 May, 66(5), 329 - 34 Comparison of the sensitivity of human and rat hepatocytes to the genotoxic effects of metronidazole; Martelli A et al.; Metronidazole (MNZ), an antiprotozoan and antibacterial agent, has been shown to yield DNA-damaging reactive species after nitroreductive biotransformation . The genotoxic effect of MNZ was studied in primary cultures of both rat and human hepatocytes . In millimolar concentrations MNZ produced DNA fragmentation, as measured by the alkaline elution technique, and unscheduled DNA synthesis, as evaluated by quantitative autoradiography, in rat hepatocytes . The amount of DNA damage was directly related to the dose and the length of exposure, was increased by hypoxia and GSH depletion, and was markedly reduced by inhibition of cytochrome P-450 activity . In the same experimental conditions human hepatocytes resulted constantly more resistant than rat hepatocytes to the genotoxic activity of MNZ . These findings suggest that the rat hepatocyte model might be an inappropriate predictor of nitroimidazoles genotoxicity. J Antibiot (Tokyo), 1990 May, 43(5), 544 - 9 Chemical modification of erythromycins . IV . Synthesis and biological properties of 6-O-methylerythromycin B; Morimoto S et al.; 6-O-Methylerythromycin B has been synthesized from erythromycin B via regioselective methylation of the 6-hydroxyl group in 71% overall yield . This compound shows in vitro antibacterial activity comparable to erythromycins A and B and exhibits superior in vivo activity with improved pharmacokinetic properties. J Antibiot (Tokyo), 1990 May, 43(5), 519 - 32 A novel carbapenem antibiotic, SM-7338 structure-activity relationships; Sunagawa M et al.; A series of new carbapenem compounds, which have a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl group at C-5' position as C-2 side chain, have been prepared . The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were discussed . In this series, SM-7338; (1R,5S,6S)-2-{(3S,5S)-5-dimethylaminocarbonylpyrrolidin-3-ylthi o}-6-{(R)-1-hydroxyethyl}-1-methylcarbapen-2-em-3-carboxylic acid (5a) was the most interesting compound. J Antibiot (Tokyo), 1990 May, 43(5), 504 - 12 Citreamicins, novel antibiotics from Micromonospora citrea: isolation, characterization, and structure determination; Carter GT et al.; A new family of antibacterial antibiotics has been isolated from Micromonospora citrea . The compounds, designated citreamicins alpha, beta, gamma, zeta and eta are of the polycyclic xanthone structure type . Their isolation, characterization and structure determination are presented. Br J Plast Surg, 1990 May, 43(3), 307 - 11 The management of exposed cardiac pacemaker pulse generator and electrode using restricted local surgical interventions; subcapsular relocation and vertical-to-horizontal bow transposition techniques; Har-Shai Y et al.; This paper describes an approach to the treatment of exposed pacemaker generator and electrode . Local infection is controlled by the administration of systemic antibiotics and topical antibacterial solutions . Because the generator and lead are enveloped by an inert synthetic coating, it is possible to eradicate an infection without their removal if it is due to a weak opportunist pathogen fully sensitive to antibiotics . Thereafter, subcapsular relocation of the exposed generator or vertical-to-horizontal transposition of the exteriorised lead is carried out . These surgical interventions are designed to overcome the vertical force which tends to cause the extrusion of the pacing hardware. J Med Chem, 1990 May, 33(5), 1470 - 6 Synthesis and biological activity of some derivatives of rifamycin P; Cavalleri B et al.; A s