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Antibiot Khimioter, 1989 Jan, 34(1), 13 - 6
{Comparison of antibiotic complexes formed by cultures of Streptomyces griseoruber}; Igina EF et al.; Physico-chemical properties of antibiotic complexes formed by various strains of Streptomyces griseoruber: VNIIA 1195, VNIIA 1193-INA 2022/55 and IMiV 1618 were compared . It was shown that the antibiotic complex 1195 differed by the electron absorption spectrum, chromatographic mobility and indicator properties from lateriomycins A and B produced by the type culture of S . griseoruber, Jamaguchi et Saburi, 1955 and strain 70717, as well as from prodigiozin produced by S . griseoruber, VNIIA 1193 . By the absorption spectra and chromatographic mobility the components of the antibiotic complex 1195 were identical with cinerubins A and B, pyrromycin and eta- and xi-pyrromycinones included in the composition of antibiotic 1618 produced by S . griseoruber 1618 and differed in their quantitative contents and absence of epsilon-pyrromycinones.

Hokkaido Igaku Zasshi, 1989 Jan, 64(1), 18 - 30
{Penetration of antibiotics into second degree burned skin in rabbits}; Yoshida T; This study was designed to determine the concentration of antibiotics administered systemically in second degree burned skin in rabbits . I: Penetration of Sulfobenzyl-penicillin (SBPC) into Deep Dermal Burn (DDB) . The concentration of SBPC was determined in the skin and serum of four groups . One group acted as control and the other three had DDB . The rabbits in each were administered 100 mg/kg of SBPC by 2 hour drip infusion . In burn groups SBPC was given on the 1st, 4th and 7th post burn day, respectively . In the control group, peak concentration in the serum and skin was obtained at the end of the drip administration decreasing quickly thereafter . In every burn group, SBPC was detected in the skin and peak concentration was obtained at the end of the drip administration . After drip infusion, the SBPC level in the skin remained longer in the burn groups than in the control group . In the first day burn group, SBPC could not be detected until 1 hour after the initiation of the drip, while in the other two burn groups, SBPC could be detected a little at 30 minutes . The SBPC skin to serum ratio at the end of the drip administration in each burn group was half the value of that in the control group . II: Penetration of Cefpiramide (CPM) into Superficial Dermal Burn (SDB) . The concentration of CPM was determined in the skin and serum of five groups . One group acted as control and the other four had SDB . The rabbits in each group were administered 20 mg/kg of CPM intravenously by bolus injection . In burn groups CPM was given at 8, 16, 24 and 48 hours, respectively, after burn inducement . As in the control group, CPM was detected in the SDB at every stage after burn inducement . However, CPM remained in the burned skin longer than in the non-burned skin . In the 16-hour-after-burn-group the CPM level reached its peak at 30 minutes after injection, while in the other three burn groups, the maximum level was achieved at 15 minutes . The CPM concentration in the skin of each burn group was the same or higher than that of the control group . III: Antibiotics systemically administered were determined in second degree burned skin . However, the degree of penetration was different according to the degree of burn.(ABSTRACT TRUNCATED AT 400 WORDS)

Biopolymers, 1989 Jan, 28(1), 409 - 20
The crystal and molecular structure of the alpha-helical nonapeptide antibiotic leucinostatin A; Cerrini S et al.; The crystal and molecular structure of the nonapeptide antibiotic leucinostatin A, containing some uncommon amino acids and three Aib residues, has been determined by x-ray diffraction analysis . The molecule crystallizes in the orthorhombic space group P2(1)2(1)2(1), a = 10.924, b = 17.810, c = 40.50 A, C62H111N11O13, HCl.H2O, Z = 4 . The peptide backbone folds in a regular right-handed alpha-helix conformation, with six intramolecular i----(i + 4) hydrogen bonds, forming C13 rings . The nonapeptide chain includes at the C end an unusual beta-Ala residue, which also adopts the helical structure of the other eight residues . In the crystal the helices are linked head to tail by electrostatic and hydrogen-bond interactions, forming continuous helical rods . The crystal packing is formed by adjacent parallel and antiparallel helical rods . Between adjacent parallel helical columns there are only van der Waals contacts, while between adjacent antiparallel helical columns hydrogen-bond interactions are formed.

Acta Urol Belg, 1989, 57(1), 35 - 46
{Modifications in spermatogenesis following antibiotic therapy}; Timmermans LM; Among eleven antibiotics with a high activity on the mitosis and on the meiosis of the seminal cells, gentamycin sulfate and cefuroxime are both the most aggressive . After 8, 15 or 30 days of treatment, a stop of the mitosis and of the meiosis, pyknosis and karyolysis are morphologically visualized in male adult rats . Histoenzymatic studies show first a decrease of the protein synthesis in the nuclei of the spermatogonia and of the spermatocytes, and second a decrease of the glucose metabolism in the spermatocytes layers . In other groups of rats treated, the sacrifice was performed after arrest of antibiotics, the morphological recuperation is slow after 8 days of treatment, none after 15 or 30 days . Histoenzymatic studies show that the recuperation of the protein metabolism is quicker than the glucose one . Arising after 8 days it can be complete after 15 to 30 days of rest . Some coincidences between these experimental works and some clinical disturbances in the fertility of men and animals after high doses of antibiotic may be pointed out.

Vestn Dermatol Venerol, 1989, (1), 4 - 7
{Endolymphatic antibiotic therapy of allergic vasculitis}; Anton'ev AA et al.; Inadequacy of the routine methods for therapy of infectious allergic vasculitides and the necessity of sanitizing the foci of infection have prompted the application of endolymphatic administration of antibiotics . Studies of ampicillin pharmacokinetics have demonstrated that a single endolymphatic injection in a dose of 1 x 10(6) U is sufficient to maintain the therapeutic concentration of the drug in the blood serum for 24 hrs . Ampicillin has been injected into the lymph vessels of both soles in the above dose once daily for 5-7 days to 10 patients suffering from allergic vasculitis for a long time . The pathologic elements regressed by the end of the course of therapy in all the cases; only two patients have developed relapses in several months, that have been rapidly arrested.

Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 113 - 8
Antibiotics for penetrating abdominal trauma: a prospective comparative trial of single agent cephalosporin therapy versus combination therapy; Bivins BA et al.; In this prospective, comparative study, 129 patients who sustained penetrating abdominal trauma were randomized to receive preoperatively, and for 3-5 days postoperatively, one of three antibiotic regimens: Group I--cefotaxime (CTX) (2 Gm Q8H), Group II--cefoxitin (2 Gm Q6H), or Group III--clindamycin (900 mg Q8H) and gentamicin (3-5 mg/kg/day in divided doses Q8H) . The three groups were similar in terms of the following: age, sex, severity of injury, number of organs injured, colon injuries, shock, blood transfusions, or positive intraoperative cultures . Septic complications occurred as follows: Group I--6.9%, Group II--2.3%, and Group III--6.9% . The three regimens ranked as follows in terms of therapy costs: CTX less than cefoxitin less than clindamycin and gentamicin . It is concluded that single agent therapy with a cephalosporin is preferable to combination therapy on the basis of equivalent effectiveness, lower toxicity, and lower costs.

Ann Chir, 1989, 43(3), 207 - 9
{Antibiotic prevention with a single dose of metronidazole in appendectomy in children}; Lansade A et al.; One hundred children were prophylactically treated with 15 mg/kg-1 of metronidazole immediately before appendicectomy and retrospectively compared with 100 other patients without any antibioprophylaxis . No statistically significant difference was found between the two groups as regards age, weight, sex and macroscopic appearance of the appendix . The overall incidence of complications was 1% in the antibioprophylactic group and 9% in the control group . Furthermore, a single pre-operative intravenous dose of metronidazole was as effective as conventional antibioprophylaxis.

J Orthop Trauma, 1989, 3(1), 6 - 10
Efficacy of antibiotics in low-velocity gunshot fractures; Dickey RL et al.; We have investigated the efficacy of intravenous antibiotic therapy as a prophylactic measure to prevent infection following low-velocity gunshot fractures . Ninety-six consecutive patients were randomized prospectively to either an antibiotic group (Group I) or a nonantibiotic group (Group II) and were followed in a special gunshot wound clinic . Only patients with fractures that could be treated by closed techniques and did not require internal fixation were included . Sixty-seven patients (73 fractures) were followed radiographically . At follow-up, 36 fractures in Group 1 and 37 fractures in Group II comprised the study group . A total of two infections, one in each group, was documented . No significant infection prophylaxis was demonstrated by the use of intravenous antibiotics in these injuries.

Drugs Exp Clin Res, 1989, 15(10), 491 - 6
Comparative effects of three beta-lactam antibiotics on anti-PC direct plaque-forming cells; Corrales I et al.; Penicillin G, cefotaxime and clavulanic acid administered intravenously were studied for their immunomodulating properties . BALBC/c mice were immunized using PC-KLH as thymus-dependent antigen at the same time as the antibiotic was injected . The effect on antibody response was evaluated 5 days after immunization . Critical immunological parameters such as direct antibody-producing cells, Ab-secretion median rate, secretion rate heterogeneity and cellular viability, were studied . The most stimulatory effects were with penicillin G at the 4 x 10(6) IU/kg dose (+73%), cefotaxime at the 366 mg/kg dose (+80%) and clavulanic acid at 1 mg/kg (+218%) . The experiments using inhibition of plaque formation with free hapten demonstrate that all the drugs studied decreased the antibody secretion rate and this parameter appeared more heterogeneous when cefotaxime and clavulanic acid were given; however, with penicillin this parameter was more heterogeneous at 2 x 10(5) mg/kg and 1 x 10(3) IU/kg respectively . When clavulanic acid was injected, the number of lymphocytes per spleen, size and friability of the spleen were increased versus the control mice . The present data show that all of the drugs studied present immunostimulating effects on humoral response, against thymus-dependent antigen, but have differently pronounced enhancements.

Pract Odontol, 1989 Jan, 10(1), 11 - 2, 14, 16 passim
{Indications and contraindications for analgesics and antibiotics in pediatric dentistry}; Palma Aguirre JA et al.; A general overview upon most used products in odontopediatrics is presented; the factors which influence the determination of the adequate doses in children and some useful recommendations in dental clinical practice are described . The most prescribed products in pediatric odontology are summarized into two groups: a) benzodiazepine, for anxiety and lidocaine, aspirin and acetaminophen, dipirone and naproxen, for pain; and b) penicillin, erythromycin, for treatment of infections . Doses, pharmacologic effects, clinical indications, side effects and contraindications of the chemicals mentioned are described . Also, the article presents some of the aspects which justify the use, in our country, of certain medicaments prescribed in other nations reporting, the recommendations in order to prevent the use of other chemicals because of their lack of therapeutical advantages over the ones of first choice.

Ther Hung, 1989, 37(2), 86 - 9
Possible interactions between antibiotics and oral contraceptives; Hetenyi G; The incidence and manifestation of drug interaction decreasing ther action of contraceptive tablets have been examined in 79 women receiving antibiotic therapy concurrently with the use of oral contraceptives . The antagonistic interaction of antibiotics manifested itself in intermenstrual spotting, rarely in break-through bleeding, but it did not completely inhibit the contraceptive action (pregnancy) . Drug interaction occurred individually and, in the majority of cases, it showed reciprocal relation to the hormone content of the used oral contraceptive . Though the exact mechanism of interaction is not known, it has to be considered in the course of therapy since both drug types are widely used.

Suppl Int J Gynecol Obstet, 1989, 2, 29 - 34
Perioperative systemic antibiotics for prophylaxis of infections in breast surgery: sulbactam/ampicillin versus mezlocillin/oxacillin; Engel K et al.; In a prospective, randomized, open trial, efficacy of one dose of sulbactam/ampicillin (1 g:2 g) was compared to three doses of mezlocillin/oxacillin (2 g:1 g), starting with induction of anesthesia in 80 breast surgery patients with an increased risk of postoperative infection . No infections at the site of operation were seen in either group . Fever due to postoperative pulmonary complications occurred in one patient in the sulbactam/ampicillin group . The only side effect was a moderate exanthema observed in one patient in the mezlocillin/oxacillin group . In this study of the prophylaxis of patients with an increased risk of postoperative infections having the potential to jeopardize the results of surgery, a single dose of sulbactam/ampicillin was as effective as a short term course of three doses of mezlocillin/oxacillin.

Schweiz Monatsschr Zahnmed, 1989, 99(8), 881 - 91
{The use of antibiotics in periodontics . A review of the literature}; Bessat JD; Since periodontal diseases are mainly of bacterial origin, the use of antibiotics could seem justified for their treatment . Numerous studies, however, have shown that these drugs are not a first choice treatment for acute and chronic periodontitis . Chemotherapy can represent a valuable adjunct to routine mechanical debridement, particularly for adult recurrent periodontitis, juvenile periodontitis and rapidly progressive periodontitis . Furthermore, prophylactic chemotherapy should be provided for patients at risk with systemic diseases, notably when congenital or acquired valvular heart defects are present . For the treatment of adult recurrent periodontitis, the most appropriate systematic drugs are, presently, tetracyclines or imidazoles . Juvenile periodontitis can be treated with the help of tetracyclines and rapidly progressive periodontitis with imidazoles . As for high risk patients, the use of various penicillins is mandatory . A decision to use antibiotics must be made only after due consideration of their potential disadvantages . One should also remember that the possible positive or negative effects of antibiotics upon the host defence mechanisms are for the moment unknown.

Mol Carcinog, 1989, 2(3), 159 - 67
Permanent conversion of mouse and human cells transformed by activated ras or raf genes to apparently normal cells by treatment with the antibiotic azatyrosine; Shindo-Okada N et al.; Azatyrosine {L-beta-(5-hydroxy-2-pyridyl)-alanine}, an antibiotic isolated from Streptomyces chibanensis, inhibited the growth of NIH 3T3 cells transformed by the activated human c-Ha-ras gene but did not significantly inhibit the growth of normal NIH 3T3 cells . Surprisingly, upon treatment with azatyrosine most of the transformed cells apparently became normal . These apparently normal cells, named revertant cells, grew in the presence of azatyrosine and stopped growing when they reached confluency, and their normal phenotype persisted during prolonged culture in the absence of azatyrosine . The revertant cells did not grow in soft agar and scarcely proliferated in nude mice . The human c-Ha-ras gene present in transformed NIH 3T3 cells was still present in the revertant cells and was expressed to the same extent as in the original transformed cells, producing the same amount of activated p21 . Treatment with azatyrosine caused similar conversion of NIH 3T3 cells transformed by activated c-Ki-ras, N-ras, or c-raf to apparently normal cells, but NIH 3T3 cells transformed by hst or ret were not exclusively converted by azatyrosine . Human pancreatic adenocarcinoma cells, which are known to contain an amplified activated c-Ki-ras gene and an amplified c-myc gene, were also converted to flat and giant revertant cells by treatment with azatyrosine.

Res Microbiol, 1989 Jan, 140(1), 69 - 73
{Early administration of antibiotic susceptible strain of Escherichia coli in the intestine of the premature infant.}; Rastegar Lari A et al.; An antibiotic-susceptible, innocuous Escherichia coli strain of human origin was administered to premature infants in order to protect them from nosocomial colonization by antibiotic-resistant enteric organisms . The strain was given to 16 untreated patients in the first six hours of life, and to 11 patients treated with antibiotics in the first six hours after cessation of treatment . The strain was able to colonize the intestinal tracts of all treated infants and 14/16 untreated infants . Colonization of these patients by antibiotic-resistant enteric organisms was compared with results obtained in a control group of 15 unadministered and untreated infants . A significant difference was recorded in the first ten days after administration . Our results show that previous antibiotic treatments did not impair intestinal colonization by an antibiotic-susceptible strain, and demonstrate the in vivo antagonistic abilities of the administered strain . Such antagonistic strains might thus be used for control of nosocomial infections of intestinal origin due to antibiotic-resistant enteric organisms.

Tierarztl Prax, 1989, 17(1), 47 - 51
{Antibiotic therapy in psittacines}; Krautwald ME; The use of different antibiotics in psittacines is described . Among other aspects especially the anatomy of the bird and its consequence for the application of medicaments is taken into account . The use of antibiotics in psittacines often turns out to be difficult because of missing data about their pharmacokinetics, dosage, period of application and their compatibility . In order to deal with the increasing number of pet-birds in the veterinary practice, further examinations have to be conducted.

Ann Rech Vet, 1989, 20(1), 3 - 15
{Appearance and evolution of bacterial resistance to antibiotics}; Guillot JF; Concomitant with antibiotic use has been the appearance of resistance bacteria which seem able to emerge as rapidly as new antibiotics are introduced . Although initially encountered in hospitals, resistant bacteria are now being detected as causes of human and animal infections and as colonizers of the gut . Moreover, resistant bacteria are isolated from the environment.

Br J Surg, 1989 Jan, 76(1), 52 - 6
Timing of prophylactic antibiotics in abdominal surgery: trial of a pre-operative versus an intra-operative first dose; Bates T et al.; When prophylactic antibiotics are used in abdominal surgery it is customary to give the first dose before the operation . Whilst intra-operative antibiotics may be effective in elective surgery, there may be an advantage to starting pre-operatively when there is already an infective focus such as appendicitis . Antibiotics started pre-operatively (group P) have been compared with antibiotics started after initial abdominal exploration (group T) . Three intravenous doses of 500 mg metronidazole plus 1 g cephazolin were given in a randomized, double-blind study of 700 emergency and elective high-risk abdominal operations . Antibiotic plasma concentrations at the end of the operation were significantly lower in group P but lay well within the therapeutic range . Wound infection rates, which included minor and delayed infections, were similar in both groups (group P, 57 of 342, 16.7 per cent; group T, 55 of 358, 15.4 per cent; 95 per cent confidence intervals for the difference being -4.1 to +6.7 per cent . In appendicitis, wound infection rates were 12.1 and 13.9 per cent for groups P and T respectively . However, non-fatal deep sepsis was more common in group P (nine cases) than in group T (two cases) (chi 2 = 4.9, P less than 0.05) . Postoperative infection was twice as common in obese patients whose body mass index (BMI) was greater than or equal to 26 (39 of 132, 30 per cent) than in thin patients whose BMI was less than 24 (41 of 288, 14 per cent; chi 2 = 13.8, P less than 0.001) . This study failed to show any advantage to starting antibiotics pre-operatively, even in appendicitis.

Yi Chuan Xue Bao, 1989, 16(6), 455 - 62
{Rapid destroying of mRNAs in disaggregated Dictyostelium cells and effect of antibiotics}; Zhou SN; Nogalamycin can inhibit RNA synthesis in both aggregated and disaggregated Dictyostelium discoideum cells . Cycloheximide and puromycin are effective in blocking translation . The late mRNAs, specific for the multicellular stage, degrade rapidly in disaggregated Dictyostelium cells . Nogalamycin or actinomycin D and daunomycin protect some of these mRNAs . Cycloheximide stabilizes all of the mRNAs, Puromycin, however, does not protect the mRNAs from destroying . These results imply that the rapid degradation of the late mRNAs during cell differentiating does not depend on nuclease or protein synthesis de novo.

Zh Nevropatol Psikhiatr Im S S Korsakova, 1989, 89(12), 78 - 82
{Pathogenetic connections between psycho-organic disorders in occupational diseases induced by exposure to antibiotics}; Gnelitskii GI et al.; Occupational diseases caused by antibiotics were studied in 104 patients . Somato-neurologic disorders with concomitant psycho-organic signs were characteristic of the ailment . The severity of the psycho-organic syndrome depended on the allergic activity, the development of systemic allergic vasculitis, pathology of cerebral circulation with developing brain organic changes, and on the severity and complexity of the somatic pathology.

Ter Arkh, 1989, 61(11), 77 - 81
{Clinical efficacy and pathogenetic validation of the intrapulmonary and intrabronchial administration of proteinase inhibitors and antibiotics in the treatment of patients with nonspecific lung diseases}; Provotorov VM et al.; Eighty patients (34 with lung abscess, 39 with lingering pneumonia associated with chronic bronchitis) were examined for the activity of the proteinase inhibitory system in bronchial washing off as well as for the level of alpha 1-proteinase inhibitor in blood serum . The system of proteinases inhibitors was found to be unbalanced with the predominance of proteinases . The proteinase inhibitor contrycal was included into the multimodality treatment of patients . The patients of the main group were administered contrycal and antibiotics intrapulmonarily with the aid of a needle jet injector (NJI-1) and endobronchially, whereas the control group patients were given intravenous injections in the identical daily and total dose . The local (intrapulmonary and endobronchial) administration of proteinase inhibitors and antibiotics turned out to compare very favourably with intravenous injection of the same remedies.

J Basic Microbiol, 1989, 29(9), 605 - 9
Relationship between the fatty acid composition and the type of antibiotics produced by Streptomyces lasaliensis; Podojil M et al.; The GC-MS method was used to analyze fatty acids in a parent strain of Streptomyces lasaliensis and its two mutants producing only lasalocid or quinomycin . The biosynthesis of these substances bears relation to differences in the relative proportion of fatty acids . Biosynthetic relationships were revealed between the starter fatty acid units, their precursors, i.e . valine, leucine and isoleucine, and the type of the antibiotic produced.

Arch Exp Veterinarmed, 1989, 43(5), 725 - 8
{The "in vitro" effect of antibiotics on mycoplasmas under conditions of the preparation of bull sperm}; Pfutzner H; Bull sperm was experimentally contaminated with Mycoplasma (M.) bovis, M . bovigenitalium, and Acholeplasma laidlawii (10(5) colony-forming units/ml sperm) . Antibiotics were tested for their effectiveness under conditions of preparation of sperm for artificial insemination, primarily for their capability of killing all mycoplasma by the end of sperm equilibration (cooling to +4 degrees C within 5 h) . Mycoplasma decontamination was achievable only by means of nourseothricin and lincospectin, in a concentration of 0.8 mg/ml sperm diluent which did not yet impair bull sperm vitality.

J Basic Microbiol, 1989, 29(6), 375 - 81
Flavovirin--a new antifungal antibiotic produced by the pyrenomycete Melanconis flavovirens; Sailer M et al.; The pyrenomycete Melanconis flavovirens was found to produce a mixture of two antifungal antibiotics . The first has been already described; the antibiotic is identical with thermozymocidin (myriocin) . The second antibiotic is a new compound, whose isolation and identification is presented in this paper . The chemical structure of this substance (C21H37NO5) was determined to be 2-amino-2-hydroxymethyl-3,4-trans-epoxy-14-oxo-eicos-trans-6-enoic acid . After the producer it was named flavovirin and it possesses strong activity against yeasts and a moderate effectivity against filamentous fungi.

Chemotherapy, 1989, 35(6), 431 - 40
Ototoxic effects of a pseudodisaccharide aminoglycoside antibiotic, dactimicin, on the inner ears of guinea pigs; Yokota M et al.; The effect of dactimicin on the inner ear of guinea pigs was investigated by comparing it with the effects of ribostamycin, astromicin and amikacin . At doses of 200 and 400 mg/kg/day for 4 weeks, no pinna reflex loss was observed, but 2 animals receiving 400 mg dactimicin/kg/day showed unilateral loss of the outer hair cells in the cochlea and very scattered loss of the hair cells in the vestibular organ . At doses of 400 and 500 mg dactimicin/kg/day for 5 weeks, all surviving animals showed no abnormality of the outer hair cells, the inner hair cells and the spiral ganglion cells in the cochlea except for scattered unilateral loss of the outer hair cells and loss of the stria vascularis . Based on these observations, it is concluded that the ototoxicity of dactimicin on the inner ear of guinea pigs is the same as or a little stronger than that of ribostamycin, weaker than or the same as that of astromicin and weaker than amikacin.

Nucleic Acids Symp Ser, 1989, (21), 53 - 4
DNA binding and cleavage by enediyne antitumor antibiotics, esperamicin and dynemicin; Shiraki T et al.; Esperamicin A1 and dynemicin represent a new class of DNA binding/damaging agents characterized by unique ten-membered ene-diyne core . The former antitumor antibiotic shows high DNA cleavage activity in the presence of dithiothreitol, whereas the latter in the presence of NADPH . Esperamicin A1 favorably breaks T and C bases at oligopyrimidine regions such as 5'-CTC, 5'-TTC, and 5'-TTT sequences . Dynemicin attacks the bases at 3'-side of purine residues such as 5'-AG, 5'-AT, and 5'-GC sequences . These drugs also present good circumstantial evidence for minor groove interaction of B-DNA.

Fundam Clin Pharmacol, 1989, 3(5), 505 - 13
Effects of acute and chronic administration of two antibiotics, aztreonam and gentamicin, alone or in combination, on "open-field test" in mice; De Angelis L; A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice . Animals were randomly assigned to two test conditions: acute and chronic treatment . Those receiving acute treatment had a single IP injection 60 min before the test . Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test . Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test . The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals . A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.

Drugs Exp Clin Res, 1989, 15(6-7), 261 - 72
Effect of glucarolactam on ototoxicity of aminoglycoside antibiotics in guinea-pigs; Yokota M et al.; Intramuscular administration of glucarolactam in the form of aminoglycoside salt to guinea-pigs protected the experimental ototoxicity caused by high dosing of aminoglycoside antibiotics . The protection was evidenced by the pinna reflex threshold and histochemical examinations of hair cells of cochlea as well as body weight gain . The degree of protection differed with the aminoglycosides, and high protection was observed for dibekacin, gentamicin, tobramycin, followed by kanamycin and bekanamycin . However, protection was weak or not observed when glucarolactam was administered as a mixture of glucarolactam potassium and aminoglycoside sulfate . Serum analysis of the guinea-pigs on day 14 post-administration as a measure of nephrotoxicity revealed that glucarolactam suppressed the elevation of BUN and serum creatinine caused by the aminoglycosides . The protective effect of glucarolactam on the aminoglycoside-induced nephrotoxicity in the dehydrated rats did not differ between the salt and the mixture . No difference in the in vivo antibiotic activity against bacterial infections of mice was observed between the salt and the mixture.

Arch Otorhinolaryngol, 1989, 246(5), 269 - 70
Gentamicin and other ototoxic antibiotics for the transtympanic treatment of Menière's disease; Lange G; Severe unilateral cases of Meniere's disease can be successfully treated with ototoxic antibiotics . Among them gentamicin sulfate gives the safest results . With the aid of a small syringe this antibiotic is introduced into the external auditory canal 5 times/day . From there it reaches the middle ear through a ventilating tube by using a Politzer bag . Gentamicin then penetrates the round and oval windows, where it influences inner ear function . Of 92 patients treated during the past 20 years, more than 90% have had no further attacks after therapy.

Scand J Infect Dis, 1989, 21(5), 551 - 6
Use of antibiotics in general practice in Denmark in 1987; Friis H et al.; The worldwide usage of antibiotics is increasing making detailed information on prescribing patterns and intervention methods necessary . This investigation focused on the general practitioner's (GP's) usage of antibiotics in Denmark . Information on 7,607 patients treated by 602 GP's during 1 week in March 1987 were collected . The most commonly treated infectious diseases were upper respiratory tract infections (40%) and lower respiratory tract infections (17%) . Penicillin was by far the most frequently prescribed antibiotic (44%), followed by antibiotics used locally (17%) and ampicillins (14%) . Compared with previous investigations, this result indicated a relative increase in prescription of penicillin during recent years . The mean number of daily dosages was 2-3 and the duration of treatment 6-7 days, with ampicillin generally given 1 day longer than penicillin . The differences between prescribed daily dosages (PDD) found and defined daily dosages (DDD) ranged from + 40% to - 50%, making estimations of numbers of treated patients from total usage of antibiotics in DDD/1,000 inhabitants/day impossible.

Scand J Infect Dis, 1989, 21(4), 449 - 57
A prospective study of infectious morbidity and antibiotic consumption among children in different forms of municipal day-care; Petersson C et al.; During the 9-month period September 1986-May 1987, reasons for absence and antibiotic consumption were investigated among children cared for in day-care center(s) (DCC) and Swedish town . family day-care (FDC) within a limited geographical area of a medium-sized Swedish town . All 352 children in 11 DCC in this area and 199 children in FDC were included in this prospective study, which intended to elucidate the infectious morbidity . The investigation period comprised 55,760 and 26,019 expected days' attendance for the DCC and FDC children, respectively . A higher absence attributable to infection was evident at all ages in DCC children than in those in FDC . This difference tended to diminish with age . No difference in antibiotic consumption was evident between the 2 categories, and the diagnostic pattern was almost identical . In the DCC, overall absence figures, and absence due to infection, were considerably lower than in earlier comparable studies . Appreciable differences in absence due to infection and antibiotic consumption were also found between different "departments" in the DCC; both low and high-absence groups could be identified . There was an indication of differences between the groups both socially and in the environment at the DCC.

Biomed Pharmacother, 1989, 43(10), 753 - 61
Potentiation by nonspecific immunostimulation of the efficacy of antibiotics in the treatment of experimental bacterial infections; Bizzini B et al.; In the present investigation, mouse infection models with either intracellular or extracellular bacteria were designed in order to assess the effect of nonspecific immunostimulation with the C . granulosum-derived P40 immunomodulator on infection treatment, performed with doses of antibiotics achieving a low percentage of cures . The results obtained showed that nonspecific immunostimulation was able to significantly enhance antibiotic therapy efficacy . In addition, combined treatments of bacterial infections should allow for a reduction in dosages of antibiotics while at the same time, achieving increased efficacy . Possible mechanisms for the potentiating effect of nonspecific immunostimulation on antibiotic therapy effectiveness are discussed.

Acta Physiol Pharmacol Latinoam, 1989, 39(4), 419 - 30
Aminoglycoside antibiotics as a tool for the study of the biological role of calcium ions . Historical overview; Corrado AP et al.; Beginning with the pioneering work of Vital-Brazil and Corrado (1957), which suggested a possible interaction between aminoglycoside antibiotics (AGA) and calcium ions at the neuromuscular junction, the authors review the studies that demonstrated the existence of a competitive antagonism between AGA and calcium ions . In view of the low liposolubility of AGA and their inability to cross biological membranes, this antagonism seems to occur exclusively at calcium-binding sites at the level of the outer opening of calcium channels of the N-subtype, which are also the sites of interaction of omega-conotoxin . Being highly water soluble, AGA are easily removed from their binding sites with a consequent rapid reversal of their effects, a factor of primary importance to explain their wide use as tools in the pharmacological analysis of the study of the biological role of calcium ion on the membrane's outer surface . This use has advantages over the use of inorganic di- and trivalent cations such as Mg2+, Mn2+, Cd2+, Ni2+, La3+, etc., since the latter, though they are considered to be the most specific competitive antagonists of calcium ions, may induce biphasic effects due to their ability to cross the membranes and replace calcium and/or increase intracellular calcium concentration . The performance of AGA is also superior when compared with the so-called "specific" organic calcium antagonists--verapamil and nifedipine derivatives--since the latter, in addition to inducing possible biphasic effects, antagonize calcium in a non-competitive manner . Finally, the authors remark that AGA-Ca2+ antagonism relevance is not limited only to basic aspects and that it may have therapeutic implications since it provides alternatives for reducing the toxic adverse effects of this important group of antibiotics.

Acta Physiol Pharmacol Latinoam, 1989, 39(4), 407 - 18
Effects of aminoglycoside antibiotics on calcium action potentials and calcium channel currents; Suarez-Kurtz G; The author reviews work from his laboratory on the effects of neomycin and streptomycin on the Ca(2+)-dependent electrogenesis of crustacean muscle fibers and on two distinct Ca2+ channel currents of pituitary cells . The data indicate that these aminoglycosides inhibit the graded electrogenesis and the action potentials of crustacean muscle; these effects are accompanied by inhibition of tension development upon membrane depolarization . Increasing the extracellular Ca2+ concentration reverses the aminoglycoside-induced blockade of the Ca(2+)-dependent electrogenesis of the muscle fibers . Neomycin blocked both the transient (T-type) and the slowly-inactivating (L-type) Ca2+ currents of clonal pituitary GH3 cells, studied with the whole cell modality of the patch clamp technique . The blockade of these currents was not modulated by activation or inactivation of the channels . Neomycin inhibited also the currents conveyed by Na+ through the slowly-inactivating Ca2+ in cells equilibrated with Ca(2+)-free media . Interpretation of these data led to the suggestion that the blockade of Ca2+ currents by neomycin (and other aminoglycosides) cannot be explained by competition with Ca2+ ions for binding to high affinity transition sites within the Ca2+ channel path.

Acta Physiol Pharmacol Latinoam, 1989, 39(4), 343 - 52
The influence of temperature and calcium concentration on the myoneural effect of antibiotics; Foldes FF et al.; To obtain information on the sites and mechanisms of the myoneural effect of aminoglycoside and polypeptide type antibiotics, the influence of neomycin, streptomycin, gentamicin and polymyxin B on the depression of the force of contraction (P) of the rat phrenic nerve-hemidiaphragm preparation was investigated at 37 degrees C, 27 degrees C or 17 degrees C and also at 37 degrees C in electrolyte solutions containing 2.5, 1.25 or 0.625 mM CaCl2 . Decreasing the temperature or the CaCl2 concentration ((CaCl2)o) of the bath significantly (p less than 0.001) decreased P . The depressant effect of aminoglycosides on P (about 50% of control at 17 degrees C) was increased more with lower temperatures than that of polymyxin B (about 20%) . The effect of lowering the (CaCl2)o on the depression of P (about 90% of control at the lowest (CaCl2)o) was about the same with the 4 antibiotics . The development of the maximal effect and the recovery of P after washout was slower with polymyxin B than with the 3 aminoglycosides . 4-Aminopyridine antagonized the depression of P caused by polymyxin B less than that caused by aminoglycosides . The findings suggest that aminoglycosides depress myoneural activity primarily by inhibiting stimulated release of ACh . Polymyxin B also inhibits ACh release, but inhibition of the contraction of myofibrils contributes more significantly to its myoneural effects than with aminoglycosides . It is conceivable that blocking of the ionophores of the postjunctional membrane also contributes to the myoneural effects of polymyxin B.

Plucne Bolesti, 1989 Jan-Jun, 41(1-2), 13 - 7
{Critical analysis of antibiotic therapy of acute respiratory infections caused by Mycoplasma pneumoniae}; Kuzman I et al.; Mycoplasma pneumoniae was the most frequently proved causative agent of pneumonia in patients hospitalized in our hospital . During the 6-year period (1980-1985), Mycoplasma pneumoniae was diagnosed in 390 patients with acute respiratory infections . Out of them 315 had pneumonia, and 75 had acute bronchitis with febrility . Pneumonia of older children and of younger adults was caused by Mycoplasma pneumoniae mostly . Most of our patients (60.77%) were treated by inadequate antibiotic therapy . In 176 (45.13%) the therapy with mostly inappropriate antibiotic started before hospitalization . This was the main reason why 165 patients (42.31%) were given two or more antibiotics . Only 126 patients (32.31%) were treated rationally with one antibiotic from the group of tetracyclines or macrolides . Doxycycline was the most effective drug, and erythromycin and midecamycin showed the very good result as well . The difference among these three antibiotics was not statistically significant (x2 = 3.188; p greater than 0.05) . However, this difference was statistically very significant in relation to penicillin (x2 = 28.082; p less than 0.001) . Penicillin was given to 62 patients (15.90%).

Kansenshogaku Zasshi, 1989 Jan, 63(1), 44 - 51
{Effect of antibiotics and anti-cancer drugs on gastrointestinal infections and dissemination by C . albicans in mice inoculated orally with C . albicans}; Suzuki H et al.; The authors studied the effect of antibiotics, hydrocortisone and anti-cancer drugs on gastrointestinal infections and dissemination by C . albicans in mice inoculated orally with C . albicans . The mice were given orally, vancomycin, amikacin and polymyxin B, and they also were injected with ampicillin and gentamicin . Hydrocortisone, cyclophosphamide (CPA) which causes leukopenia and neutropenia, and methotrexate (MTX) which injures the mucous membrane of the gastrointestinal tract were injected to the mice . In the mice treated with antibiotics and anti-cancer drugs, and inoculated orally with C . albicans, the colony forming units of the feces conspicuously increased . Gastrointestinal candidiasis was frequently observed, particularly at the cardia and the cardio-antrum line of the stomach of these mice . In addition to these sites, gastrointestinal candidiasis was observed at the antrum and the small intestine of the mice injected with MTX . C . albicans was frequently recovered from the livers and lungs of the mice treated with antibiotics and MTX + CPA which cause leukopenia, neutropenia and the damage of mucous membrane of the gastrointestinal tract . It is suggested that the threshold gut population of C . albicans is a determinant for gastrointestinal candidiasis, and that leukopenia, neutropenia and the damage of mucous membrane of the gastrointestinal tract are important factors for dissemination by C . albicans from the primary gastrointestinal lesions.

Arch Tierernahr, 1989 Jan-Feb, 39(1-2), 97 - 104
Effect of some antibiotics as growth promoters on performance of broiler chicks fed different protein levels; Abdel Hakim NF et al.; This work was carried out to study the effect of different sources of dietary antibiotics (Zinc bacitracin, Flavomycin, Virginiamycin) in rations with optimal protein levels (starter phase: 23.5%, finisher phase: 20.0%) and low protein levels (starter phase: 19.6%, finisher phase: 17.0%) on broiler performance with 8 groups of 75 broiler each . The supplement of diets, containing the optimal and low protein level, with antibiotics increased the body weight after 7 weeks of age and improved the feed conversion as compared with control groups . Virginiamycin was superior in increasing body weights after 7 weeks of age and in improving the feed conversion with rations containing low protein level when compared with zinc bacitracin and Flavomycin . When broiler rations, low in the protein content, were supplemented with antibiotics, they could not substitute the difference in optimal protein level . Antibiotics supplementation increased the value of improvement in production efficiency and this was more pronounced with Virginiamycin.

Prog Clin Biol Res, 1989, 289, 217 - 27
The solution conformation of the antibiotic anticancer chromomycin A3 by two-dimensional NMR spectroscopy; Berman E et al.; The solution conformations of chromomycin A3 (CRA) and dechromose-A chromomycin A3 (CRA-B) in dichloromethane and methanol were studied by two-dimensional (2D) NMR techniques . In dichloromethane, the drugs are found in a compact wedged-like conformation, with the phenolic hydroxyls at the tip and the side chains folded back to one side of the aglycon plane, oriented parallel to each other . The overall structure is stabilised by intramolecular hydrogen bonds and by the formation of a hydrophobic pocket, enclosed by the three side chains . In methanol, the drugs have the expected open conformation with extended side chains . Like its parent drug, CRA-B binds to d(ATGCAT)2 duplex with a major groove orientation, a 2:1 drug/duplex ratio and a two-fold symmetry of the resultant complex . The drug molecule is suggested to reside diagonally across the two strands of the duplex and to span 3 base pairs, while all three side chains of the drug are folded away from the major groove of the DNA . The observed nonequivalent positions of CRA and CRA-B within the major groove of the duplex results from the different conformation adopted by the sugar side-chains in the two complexes.

J Pak Med Assoc, 1989 Jan, 39(1), 9 - 12
Use of prophylactic antibiotic in clean surgical cases--a prospective trial of various regimens; Sultan S et al.; In a randomised controlled prospective trial, different antibiotic regimens were evaluated as prophylaxis in wound infection following elective surgical procedures . Four hundred and four consecutive cases were divided in four groups . Two groups were allotted two different conventional postoperative antibiotic regimens while the fourth group received short term perioperative antibiotic; group one served as control . A higher frequency of postoperative wound infection was observed in the controls . Results showed reduction in gross infection in only group III where short term perioperative antibiotic was used . Combination of penicillin and streptomycin were not found effective, and low infection rate was observed with Cephamendole used perioperatively.

Biochimie, 1989 Jan, 71(1), 49 - 56
Interaction of the polyene antibiotic amphotericin B with model membranes: differences between small and large unilamellar vesicles; Milhaud J et al.; The interaction of the polyene antibiotic amphotericin B (AmB) (Fig . 1) with large unilamellar vesicles (LUV) was monitored by circular dichroism (CD) and carboxyfluorescein (CF) release . LUV afford a far better model for biological membranes than small unilamellar vesicles (SUV) which have been used until now . With dimyristoyl phosphatidyl choline (DMPC) LUV (i.e., containing saturated acyl chains), a strong and not saturable binding for AmB/lipid ratios up to 0.5 was observed both above and below the phase transition temperature . Incorporation of cholesterol into the vesicles did not significantly change the interaction . With egg PC (EPC) LUV (i.e., containing unsaturated acyl chains), quite a different picture emerged: the binding reached saturation for AmB/lipid ratios of about 5 x 10(-3), a result not observed with EPC SUV . When sterols were introduced into membranes, the CD spectral features obtained in the presence of ergosterol were different from those obtained in the presence of cholesterol . Such a different behavior was not observed with SUV . We suggest that species whose CD spectrum was observed after 15 min in the presence of ergosterol-containing EPC LUV is the particular one which forms wide channels and induces a Ca2+ release . (H . Ramos, A . Attias, B.E . Cohen and J . Bolard, submitted for publication) . The CF release from EPC LUV induced by AmB was very low, even at very high concentrations of the antibiotic (3 x 10(-4)M) . In contrast, an important release of the fluorescent dye was observed with DMPC LUV at concentrations of approximately 10(-5)M.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochimie, 1989 Jan, 71(1), 125 - 35
Study of a delta-hydroxy ketone-hemiketal equilibrium by 2D-NMR exchange spectroscopy for the antibiotic grisorixin: involvement in cationic transport through membranes; Beloeil JC et al.; Study of a delta-hydroxyketone-hemiketal equilibrium in the polyether antibiotic grisorixin was performed with 2D-NMR spectroscopy . The efficiency of 13C chemical exchange spectroscopy for the assignment of 1H and 13C resonances, in the 2 forms, was shown, making possible a conformational investigation of both forms . This equilibrium was observed for grisorixin in solvents of varying polarity, such as CD2Cl2, CDCl3, CD3CN, or CD3OD, but not in C6D12 or C6D6 . Other related antibiotics with the same terminal heterocycle were described only in the closed hemiacetalic structure . The low ionic fluxes measured in a bulk chloroformic membrane for grisorixin were explained by this equilibrium, which competed unfavorably with the cation capture process at the water-chloroform interface . This equilibrium would not be present in a phospholipidic bilayer membrane containing the ionophore, published experimental results are taken into account . The peculiar tautomeric equilibrium observed for grisorixin could be linked to the specific axial stereochemistry of the C7-C8 bond, which creates tension in the globular conformation.

J Pharm Biomed Anal, 1989, 7(12), 1829 - 35
Determination of residues of tetracycline antibiotics in animal tissues by high-performance liquid chromatography; Mulders EJ et al.; A method has been developed for the determination of tetracycline (TC), oxytetracycline (OTC), chlortetracycline (CTC) and doxycycline (DC) in animal tissues . Tissues were macerated with a buffer solution and centrifuged . The supernatant solution was purified over a Sep-Pak C18 cartridge which had previously been deactivated by silylation . Tetracyclines were eluted with methanol, the solvent evaporated and the residue dissolved in the HPLC mobile phase . Compounds were separated on a Novapak Phenyl Radial-Pak cartridge with a Resolve CN guard column using gradient elution and UV detection . The method was tested on chicken, porcine and bovine muscle . Recoveries were determined for OTC, TC, CTC and DC added to porcine, bovine and chicken muscle at levels of 0.05 and 0.2 mg kg-1 . They varied from about 90% for OTC to about 68% for DC with coefficients of variation of 1.8-7.5% . The limit of determination is 5-10 micrograms kg-1 . The method was validated on tissues of laying-hens after intramuscular injection of OTC.

J Pharm Biomed Anal, 1989, 7(10), 1159 - 64
The ultraviolet derivative spectrophotometric determination of neutral liposome-entrapped beta-lactam antibiotics; Di Giulio A et al.; A simple, non-invasive spectrophotometric assay to measure the concentration of some beta-lactam antibiotics in turbid solutions containing liposomes was carried out . Since zero-order spectra gave strong interference because of sample turbidity, derivative spectrophotometry was used to enhance the spectral details . Derivative spectra showed bands in the ultraviolet region due to the presence of the cephalosporin and penicillin beta-lactams . A linear relationship between derivative amplitudes and antibiotic concentration was found when antibiotic-containing liposome solutions were measured . A saturative trend in the liposome-encapsulation was observed . The antibiotic entrapment was lowered by increasing the cholesterol-phospholipid ratio in the mixture used for liposome preparation . After treatment of antibiotic-loaded liposomes with beta-lactamase, a hydrolytic enzyme specific for beta-lactams, the remaining antibiotic concentration decreased significantly, showing that some of the antibiotic was retained on the outer surface of the vesicles.

J Pharm Biomed Anal, 1989, 7(10), 1121 - 57
Mass spectrometry of beta-lactam antibiotics with special reference to ionization by fast atom bombardment (FAB); Casy AF et al.; The mass spectral characteristics of the majority of penicillin and cephalosporin beta-lactam antibiotics in world-wide clinical use are presented and reviewed . Special attention is given to the spectra recorded under fast atom bombardment (FAB) conditions and novel data on many penicillins and cephalosporins are included . Mass spectrometry features of common degradation products of benzylpenicillin and of some synthetic intermediates are also presented . The data illustrate the value of FAB mass spectrometry in identifying members of this closely related group of antibiotics without need for derivatization.

J Pharm Biomed Anal, 1989, 7(3), 303 - 8
Drug analysis by near-infra-red reflectance spectroscopy . Determination of the active ingredient and water content in antibiotic powders; Lonardi S et al.; Near-infra-red reflectance spectroscopy is used to determine the active ingredient concentration and water content of an antibiotic powder (ceftazidime pentahydrate) . The validity of predictive models for active ingredient concentrations and water content, constructed by means of the multiple linear regression technique is discussed . A procedure is devised for the analysis of production samples, which, on account of the very limited range of concentrations, prove a difficult fit to the above-mentioned model . The results obtained in testing formulation samples from 1 year's industrial production are used to illustrate the potential of the technique.

Hell Stomatol Chron, 1989 Jan-Mar, 33(1), 27 - 32
{Effect of antibiotic administration on the healing of replanted teeth . Experimental investigation in dogs}; Lambrianidis T et al.; Administration of antibiotics is usually recommended when an avulsed tooth is replanted although: a . no immediate acute infection as a consequence of tooth replantation has been known, b . their administration following tooth replantation has been questioned . The purpose of this experimental study was to investigate the effect of antibiotic administration on the healing of replanted teeth . 16 maxillary and mandibular permanent lateral incisors of four dogs aged from 5 to 7 months were immediately replanted without endodontic treatment . Oxytetracycline was administered intramuscularly the day of the experiment and twice daily through the experimental period in two of the dogs (8 teeth) . The animals were sacrificed so as to provide observation periods of 15 and 22 days . Results were evaluated histopathologically in haematoxyline eosine stained sections . Results obtained showed shallower resorptine cavities without inflammatory cells in the experimental group (administration of antibiotics) than those found in the control group where inflammatory cells were also present.

Aust Clin Rev, 1989, 9(3-4), 146 - 8
Use of peri-operative antibiotics in abdominal surgery: a criterion audit; Hall JC et al.; OBJECTIVE . To evaluate the peri-operative use of parenteral antibiotics in 100 patients undergoing abdominal surgery . METHOD . Prospective criterion audit . RESULTS . There is a need for the close monitoring of antibiotic usage within hospitals, because 39% of the patients received inappropriate antibiotic therapy.

Arch Immunol Ther Exp (Warsz), 1989, 37(1-2), 183 - 9
Influence of selected antibiotics on interferon synthesis; Zielinska-Jenczylik J et al.; This paper discusses the influence of antibiotics - penicillin, streptomycin and mitomycin C - on interferon synthesis in vivo and in vitro . None of the antibiotics investigated was interferon inducer either in the suspension of human leukocytes or in the culture of cutaneo-muscular tissue from human embryo (HAT), or in mouse organism . However, the in vitro experiments revealed inhibitory effect of streptomycin and mitomycin C on the production of Newcastle disease virus (NDV) - stimulated interferon . Noteworthy is that the inhibition was most pronounced when the drug was administered simultaneously with the virus in the case of streptomycin or 24 h before the inducer in the case of mitomycin C . On the other hand, penicillin when introduced to the culture, exerted negligible modulatory effect on NDV-stimulated IFN.

Nucleic Acids Symp Ser, 1989, (21), 51 - 2
DNA strand scission by antitumor antibiotics . Detection of C-4'-hydroxylated abasic sites in DNA; Sugiyama H et al.; Detection of C-4'-hydroxylated abasic site in calf thymus DNA was investigated . Upon heating with neutral hydrazine (90 degrees C, 5 min) C-4'-hydroxylated abasic site formed by photo-excited Co(III)bleomycin was converted to the fragments having 3'-phosphoro-3''-pyridazinylmethylate as illustrated on Scheme 1 . Subsequent enzymatic digestion of the reaction mixture provided four kinds of pyridazine mononucleotides (1, 2, 3, and 4) . The fact that the amount of free bases released from calf thymus DNA corresponded well to the amount of pyridazines indicates this reaction can be used for detection of C-4'-hydroxylated abasic site in DNA . By this assay, we first identified the formation of C-4'-hydroxy abasic sites in calf thymus DNA by neocarzinostatin.

Biomed Biochim Acta, 1989, 48(5-6), S552 - 7
Effects of channel-forming antibiotics on the membrane of skeletal muscle fibre; Caffier G et al.; Gramicidin A, amphotericin B and nystatin increased the cation conductance and efflux rates from frog skeletal muscle fibres . Concerning gramicidin A, the characteristics tested are similar to those reported for BLM . Therefore, a channel formation like that in BLM is assumed for the muscle cell membrane . On the other hand, the kinetics of channel formation are different in muscle membrane and BLM . This suggests that the processes which limit the rate of channel formation are different.

Neurosurg Rev, 1989, 12(1), 31 - 9
Frontobasal and orbital reconstruction following trauma and tumor removal using a compound of bone meal, antibiotic, and fibrin sealant; Knoringer P; In the treatment of fronto-basal cerebrocranial trauma and primary or secondary orbital tumors, definitive surgical intervention in one sitting has proven very successful . The orbital roof, the lateral orbital walls, and the frontal base are reconstructed with a bone meal/fibrin sealant plastic, whereas the orbital rims are revised using available bone fragments refitted using osteosynthetic procedures . Remaining calotte defects are covered alloplastically with Refobacin-Palacos . Bones can be easily remodeled with the bone meal/fibrin sealant plastic . The fibrin sealant holds the shape in regions not subject to mechanical stress, and contributes to an immediate, watertight closure . The addition of an antibiotic achieves effective prophylaxis against infections in the initial phase . The result is an autologous bone which provides a maximum of protection against late infections such as occur in alloplasties and against ascending infections with meningitis, as observed in unreconstructed bone defects . Since the bone meal is usually obtained during trepanation, bone biopsies of other body regions are unnecessary.

Biopolymers, 1989 Jan, 28(1), 259 - 66
Structure of the ion channel peptide antibiotic gramicidin A; Langs DA; The crystal structure of the uncomplexed orthorhombic form of gramicidin A has been determined at 0.86 A resolution . The polypeptide crystallizes from ethanol as a left-handed, double-stranded, antiparallel beta 5.6-helical dimer that is 31 A long and an average of 4.8 A in diameter . The uncomplexed channel does not contain ions or solvent molecules, and its diameter is not uniform but varies from a minimum of 3.85 A to a maximum of 5.47 A . There are three empty cavities in the channel that have a diameter exceeding 5.25 A and appear to be large enough to accommodate water molecules or potassium ions in a chemically reasonable coordination environment . The observed crystal structure does not offer any obvious clues as to why an antiparallel beta 5.6-helix cannot function as an ion channel in lipid bilayers.

J Antibiot (Tokyo), 1989 Jan, 42(1), 107 - 15
Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA polymerases; Take Y et al.; The inhibition of human immunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compounds was studied in comparison with that of avian myeloblastosis virus (AMV) reverse transcriptase and cellular DNA polymerases alpha and beta . In general, compounds that inhibited HIV reverse transcriptase also inhibited AMV reverse transcriptase . For example, 10 micrograms/ml of the isoquinoline quinones used in this study inhibited approximately 80% of the activity of reverse transcriptases of HIV and AMV, but did not inhibit the activity of DNA polymerases alpha and beta even at 50 micrograms/ml . AMV enzyme was more sensitive than HIV enzyme to colistin, enduracidins A and B, janiemycin, glysperin A, and thielavins A and B . The streptonigrin alkyl esters, however, inhibited HIV reverse transcriptase only . Sakyomicin A, luzopeptins, ellagic acid and suramine inhibited the activities of reverse transcriptases and cellular DNA polymerases.

Gene, 1988 Dec 30, 74(2), 305 - 20
Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor; Hallam SE et al.; The BamHI fragment containing the actIII gene, from the actinorhodin (Act) biosynthetic gene cluster of Streptomyces coelicolor A3(2), was sequenced . The derived amino acid sequence for the actIII gene shows homology to known oxidoreductases and the actIII product is believed to be responsible for catalysing a beta-keto reductive step during assembly of the Act polyketide chain . High resolution transcript mapping identified the transcription start point at 33 nucleotides upstream of the putative translation start codon . The transcript ends in a large invertedly repeated sequence . In vivo promoter-probe studies suggest that efficient transcription of the actIII gene requires the product of the actII gene.

Biochem Biophys Res Commun, 1988 Dec 15, 157(2), 692 - 7
The polyene antibiotic amphotericin B inhibits the Na+/K+ pump of human erythrocytes; Vertut-Doi A et al.; The polyene antibiotic Amphotericin B is known to induce K+ loss from human erythrocytes . In the present study it is shown that this efflux is not solely due to the formation of pores through the membrane but also to the inhibition of the Na+/K+ pump . At 5 microM this inhibition is total . The interaction of Amphotericin B with membrane enzymes is therefore to be taken into consideration when trying to explain its mechanism of action.

J Biomol Struct Dyn, 1988 Dec, 6(3), 489 - 502
Molecular structure, conformation and interactions of antitumor antibiotic cyanonaphthridinomycin, a covalent binder of DNA; Arora SK et al.; X-ray, NMR and molecular modeling studies on cyanonaphthridinomycin (C22H26N4O5), a DNA binding antibiotic, have been carried out to study the structure, conformation and interactions with DNA . The crystals belong to the space group P21 with the cell dimensions of a = 5.934(1)b = 20.684(4), c = 16.866(3)A, gamma = 90.9 degrees and Z = 4(two molecules/asymmetric unit) . The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.087 for 4061 reflections . The conformation of the molecule is compared with that of naphthridinomycin . There are differences in the orientation of the methoxyl group and the saturated oxazole ring . 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure . Molecular mechanics studies were carried out to obtain the energy minimized structure and its comparison with X-ray and NMR results . Molecular modelling studies were performed to propose models for drug-DNA interactions . Both partial intercalation and groove-binding models have been proposed.

J Biomol Struct Dyn, 1988 Dec, 6(3), 459 - 70
Interaction of the antitumor antibiotic mitomycin C with Z-DNA; Chawla AK et al.; Mitomycin C (MC), an antitumor antibiotic, alkylated Z-DNAs such as poly(dG-dC)/Co(NH3)3+(6), poly(dG-m5dC)/Mg2+ and brominated poly(dG-dC) upon reductive activation . Computer-generated energy-minimized molecular models indicated that monofunctional alkylation of Z-DNA at the N2-position of guanine by MC did not distort Z-DNA geometry, but bifunctional alkylation, leading to interstrand crosslinks between two N2-positions of guanine was sterically unfavorable . The above three Z-DNA's were exposed both to monofunctionally and bifunctionally activated MC in separate experiments and the resulting covalent MC-polynucleotide complexes were examined for conformation and for covalent MC-adducts, by circular dichroism (CD) spectroscopy and HPLC analysis of nuclease digests, respectively . Monofunctionally activated MC alkylated all three polynucleotides in their Z-forms, resulting in the same monofunctional N2-guanine adduct as that known to be formed with B-DNA . Upon bifunctional activation of MC, poly(dG-dC/Co(NH3)3+(6) reverted to the B-form and bifunctional (cross-link) adducts were detected, identical again with those formed with B-DNA . Poly(dG-m5dC), however, remained in the Z-form after the alkylation and only a monofunctional adduct could be detected . It was concluded that Z-DNA is subject to monofunctional alkylation by MC but cannot be cross-linked . The latter process occurs only when the Z-DNA is labile enough {as is in the case of poly(dG-dC)} to have some B-form in equilibrium at the site of the first formed monolinked adduct; the cross-linking then occurs at such local B-sites, pulling the overall B in equilibrium Z equilibrium irreversibly to the left . These results are in accord with the predictions from the above modeling . The irreversible "lock" by the MC cross-link on B-DNA may be exploited for probing Z-DNA intermediacy in various DNA functions.

Doc Ophthalmol, 1988 Dec, 70(4), 301 - 8
Nontoxic concentration of antibiotics for intravitreal use--evaluated by human in-vitro ERG; Kawasaki K et al.; The effects of penicillin G (PC-G) sodium, procaine PC-G, cloxacillin sodium (MCIPC), disodium sulbenicillin (SBPC), cefazolin sodium (CEZ), gentamicin sulfate (GM) and fosfomycin sodium (FOM) on the electroretinogram (ERG) of the human in-vitro eye-cup were studied . The oscillatory potentials (OPs) were selectively and greatly suppressed by 1.0 mM PC-G sodium . The OPs and c-wave were suppressed by 0.85 mM procaine PC-G . The b-wave and OPs were slightly suppressed by 1.0 mM MCIPC . The a-wave, b-wave, OPs and c-wave were not deteriorated by 1.0 mM SBPC . The OPs appeared to be selectively suppressed by 1.0 mM CEZ . The b-wave was suppressed and the peak latencies of the OPs were delayed by 184 micrograms/ml (approximately 0.4 mM) GM . The amplitudes of the a-wave and c-wave were slightly enhanced and their peak latencies were slightly delayed by 184 micrograms/ml GM . The a-wave, b-wave, OPs and c-wave were not deteriorated by 1.0 mM FOM . The results of the present study on the human retina were comparable to those on the albino rabbit retina in our previous studies.

Antibiot Khimioter, 1988 Dec, 33(12), 903 - 5
{DNA liquid crystals as a possible system of testing the interactions between DNA and biologically active compounds of platinum (II) and various antibiotics}; Evdokimov IuM et al.; DNA liquid crystals forming in water-salt solutions containing polyethylene glycol were used as a system for testing consequences of reactions of antitumor compounds belonging to two different groups with molecules of nucleic acids . It was found that with due account of the level of DNA molecule filling with daunorubicin it was possible to form two cholester phases characterized by the textures of "finger prints" and CD spectra with intensive bands of unlike signs, as well as the nematic phase characterized by the texture of the "black twisted fiber" system and the absence of the CD spectrum intensive band . Modification of the DNA molecules resulting from the reaction with cysdichlorodiamine platinum (II) led to formation of a new liquid crystalline phase with properties differing from those of the liquid crystalline phases of the cholester or nematic type.

J Antibiot (Tokyo), 1988 Dec, 41(12), 1785 - 94
Aranorosin, a novel antibiotic from Pseudoarachniotus roseus . II . Structure elucidation; Fehlhaber HW et al.; Aranorosin, a new antifungal antibiotic, has been isolated from the culture filtrate and mycelium of a strain of Pseudoarachniotus roseus Kuehn . The antibiotic, C23H33NO6, contains a novel 1-oxaspiro{4,5}decane ring system . The structure (I) has been elucidated on the basis of spectroscopic and chemical analysis.

J Antibiot (Tokyo), 1988 Dec, 41(12), 1758 - 62
Taxonomic studies on Kitasatosporia cystarginea sp . nov., which produces a new antifungal antibiotic cystargin; Kusakabe H et al.; Taxonomic studies on a new species, Kitasatosporia cystarginea are presented . Among the several species already described in this genus, this strain is characteristic in forming distinct spirals of spore chains . A significant properties of the species is the production of a new antifungal antibiotic, cystargin.

Can J Microbiol, 1988 Dec, 34(12), 1297 - 303
Induction of tyrosinase by L-methionine in Streptomyces antibioticus; Katz E et al.; Investigations were carried out to establish conditions favorable for the formation of tyrosinase, an inducible metalloenzyme synthesized by Streptomyces antibioticus . It was determined that the size of the inoculum and age of the culture as well as the temperature of incubation were important factors for enzyme synthesis . Induction of tyrosinase by S . antibioticus appears to be specific for L-methionine with maximal enzyme synthesis observed at 0.1 mM . Addition of CuSO4 and D-glucose at the time of induction also are important for increased enzyme activity . Inhibition of tyrosinase synthesis was observed with actinomycin D, rifampicin, and chloramphenicol suggesting that both transcriptional and translational events are required for tyrosinase induction.

J Antibiot (Tokyo), 1988 Dec, 41(12), 1812 - 22
Chemical modification of the antitumor antibiotic glidobactin; Oka M et al.; A variety of glidobactin analogs modified at the fatty acid, L-threonine and nucleus moieties of the molecule were synthesized and their structure-activity relationships examined . The antitumor and antifungal activity was greatly influenced by modification of the fatty acid glidobactin, with the dodecanoyl and tetradecanoyl analogs exhibiting better antitumor activity than the parent antibiotics . Replacement of the L-threonine with other amino acids greatly reduced the activity and reduction of the double bond of the nucleus completely eliminated the biological activity of glidobactin.

Farmaco {Sci}, 1988 Dec, 43(12), 1005 - 18
Isolation and structure determination of the main related substances of teicoplanin, a glycopeptide antibiotic; Cometti A et al.; Teicoplanin is a complex formed by five closely related glycopeptides and by a small amount of a hydrolysis product . Minor quantities of related substances are also present . Two of them (named RS-1 and RS-2) were isolated and purified starting from the tailing fractions of a teicoplanin batch . Preparative reversed-phase liquid chromatography on large low-pressure and medium high-pressure scales, concentration, desalting, and freeze-drying steps were applied . 300 mg of RS-1 and 900 mg of RS-2 were obtained in a purity grade (about 90%) sufficient for structural investigation . Starting from considerations on the HPLC retentivity and on biosynthesis, the structures were assigned on the basis of 1H-N.M.R . spectra and homonuclear CO-SY 2D experiments, FAB-MS spectrometry, and GC-MS of the esters of the fatty acids obtained by hydrolysis . RS-1 and RS-2 are teicoplanins having 10-methyl-undecanoic acid and n-dodecanoic acid, respectively as fatty acid chains . No major difference in the in vitro activity of these teicoplanins emerged in comparison with teicoplanin complex.

J Bacteriol, 1988 Dec, 170(12), 5416 - 22
marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli; Cohen SP et al.; Mar (multiple antibiotic resistant) mutants of Escherichia coli express chromosomally mediated resistance to a variety of structurally unrelated hydrophilic and hydrophobic antibiotics . Insertion of transposon Tn5 into the marA locus at min 34.05 on the chromosome completely reverses the Mar phenotype (A . M . George and S . B . Levy, J . Bacteriol . 155:531-540, 1983) . We found that among changes in the outer membrane of Mar mutants, porin OmpF was greatly reduced, although Mar mutants were more resistant than cells lacking only OmpF . Transduction of the marA region from a Mar strain, but not a wild-type strain, led to loss of OmpF . P1 transduction of marA::Tn5 into a Mar mutant partially restored OmpF levels . Therefore, OmpF reduction required a mutation in the marA region . Mar mutants of an ompF-lacZ operon fusion strain expressed 50 to 75% of the beta-galactosidase activity of the isogenic non-Mar parental strain, while Mar mutants of a protein fusion strain expressed less than 10% of the enzyme activity in the non-Mar strain . These changes were completely reversed by insertion of marA::Tn5 . The responsiveness of OmpF-LacZ to osmolarity and temperature changes was similar in Mar and wild-type strains . Although some transcriptional control may have been present, OmpF reduction appeared to occur primarily by a posttranscriptional mechanism . The steady-state levels of ompF mRNA were twofold lower and the mRNA was five times less stable in the Mar mutant than in the wild-type strain . Expression of micF, which lowers ompF mRNA levels, was elevated in Mar strains, as revealed by a micF-lacZ fusion . Studies with strains deleted for the micF locus showed that the marA-dependent reduction of OmpF required an intact micF locus . Our findings suggest that the marA locus directly or indirectly increases micF expression, causing a posttranscriptional decrease in ompF mRNA and reduced amounts of OmpF.

Proc R Soc Lond B Biol Sci, 1988 Nov 22, 235(1279), 121 - 38
The Leeuwenhoek lecture, 1987 . Towards an understanding of gene switching in Streptomyces, the basis of sporulation and antibiotic production; Hopwood DA; Streptomycetes are soil bacteria that differ from the genetically well-known Escherichia coli in two striking characteristics . (1) Instead of consisting of an alternation of growth and fission of morphologically simple, undifferentiated rods, the streptomycete life cycle involves the formation of a system of elongated, branching hyphae which, after a period of vegetative growth, respond to specific signals by producing specialized spore-bearing structures . (2) The streptomycetes produce an unrivalled range of chemically diverse 'secondary metabolites', which we recognize as antibiotics, herbicides and pharmacologically active molecules, and which presumably play an important role in the streptomycete life cycle in nature . This 'physiological' differentiation is often temporally associated with the morphological differentiation of sporulation and there are common elements in the regulation of the two sets of processes . In the model system provided by Streptomyces coelicolor A3(2), the isolation of several whole clusters of linked antibiotic biosynthetic pathway genes, and some key regulatory genes involved in sporulation, has made it possible to study the basis for the switching on and off of particular sets of genes during morphological and 'physiological' differentiation . Genetic analysis clearly reveals a regulatory cascade operating at several levels in a 'physiological' branch of the differentiation control system . At the lowest level, within individual clusters of antibiotic biosynthesis genes are genes with a role as activators of the structural genes for the pathway enzymes, and also resistance genes . It is attractive to speculate that the latter play a dual role: protecting the organism from self-destruction by its own potentially lethal product, and forming an essential component of a regulatory circuit that activates the biosynthetic genes, thus ensuring that resistance is established before any antibiotic is made . A next higher level of regulation is revealed by the isolation of mutations in a gene (afsB) required for expression (probably at the level of transcription) of all five known secondary metabolic pathways in the organism . At a higher level still, the bldA gene, whose product seems to be a tRNA essential to translate the rare (in high {G + C} Streptomyces DNA) TTA leucine codon, controls or influences the whole gamut of morphological and 'physiological' differentiation, because bldA mutants fail to produce either secondary metabolites or aerial mycelium and spores, while growing normally in the vegetative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Vet Rec, 1988 Nov 19, 123(21), 542 - 3
Infection rates in clean surgical procedures with and without prophylactic antibiotics; Klein WR et al.; One hundred calves with an uncomplicated umbilical hernia were included in a prospective study . The frequency of wound infection and recurrence of herniation were compared in animals operated on either with or without prophylactic antibiotics . In 90 calves operated on for the first time (60 without antibiotics and 30 with antibiotics) there were no infections and only one hernia recurred . In 10 calves operated on for the second time (seven without antibiotics and three with antibiotics) there were two infections and one hernia recurred in the group not receiving antibiotics.

Biochem J, 1988 Nov 15, 256(1), 271 - 8
1H- and 13C-n.m.r . studies of the antitumour antibiotic luzopeptin . Resonance assignments, conformation and flexibility in solution; Searle MS et al.; The depsipeptide DNA-intercalating antibiotic luzopeptin was studied in solution by n.m.r . methods . Two-dimensional 1H double-quantum-filtered correlation spectroscopy (DQF-COSY) and nuclear-Overhauser-effect spectroscopy (NOESY) confirm the primary structure and twofold symmetry of luzopeptin and provide details of its three-dimensional conformation in solution . Trans-annular hydrogen bonds between the glycine NH groups and carbonyl oxygen atoms have been identified in the crystalline state {Arnold & Clardy (1981) J . Am . Chem . Soc . 103, 1243-1244}, and are important in maintaining an antiparallel beta-sheet conformation . The n.m.r . data indicate that the glycine NH protons are appreciably shielded from the solvent molecules, which suggests that these hydrogen bonds are maintained in solution . The orientation of the quinoline chromophores is defined by two-dimensional NOE cross-peaks that position the N-methyl group of the L-beta-hydroxyvaline residue close in space to both the quinoline H-8 and serine NH proton . This pattern of NOEs is in accord both with the chromophore configuration found in the crystal and one where the quinoline rings are aligned in a parallel manner at right-angles to the depsipeptide ring . The n.m.r . data are consistent with a hydrogen bond between the quinoline hydroxy groups and the quinoline carbonyl oxygen atoms . The pyridazine acetylmethyl groups give NOEs to the C(alpha)H groups of the beta-hydroxy-N-methylvaline residues, showing that the acetyl groups, for at least some of the time, stretch over the depsipeptide ring, occluding one face of the molecule . Both of the latter features are also found in the crystal structure . Resonances in the 13C-n.m.r . spectrum of luzopeptin have been assigned by transferring 1H assignments to their covalently bonded carbon atoms via a heteronuclear shift-correlation experiment (HETCOR) . The measurement of spin-lattice relaxation times and 1H-13C NOEs at specific sites in the molecule has led us to conclude that segmental motions within the depsipeptide ring are restricted and that the 13C relaxation data for luzopeptin's protonated carbon atoms are adequately described by isotropic tumbling in solution . Furthermore, relaxation data for the carbon atoms of the quinoline chromophores show that these rings exhibit similar motion to the depsipeptide ring and are not rotating rapidly with respect to it . Taken together all the data imply that luzopeptin is fairly rigid in solution, on the time scale of molecular tumbling, and has, or can readily attain, a staple-like structure suitable for bisintercalation.(ABSTRACT TRUNCATED AT 400 WORDS)

Biochim Biophys Acta, 1988 Nov 10, 951(1), 213 - 9
DNA sequence analysis of the Olir2-76 and Ossr1-92 alleles of the Oli-2 region of the yeast Saccharomyces cerevisiae . Analysis of related amino-acid substitutions and protein-antibiotic interaction; Ray MK et al.; Petite deletion mapping helped to generate a fine-structure genetic map of the Oli-2 region of the mitochondrial genome of Saccharomyces cerevisiae . Here we report the DNA sequence analysis of the Oli-2 region from two drug-resistant alleles (Olir2-76 and Ossr1-92) which are located in the gene for subunit-6 of mitochondrial ATPase, in agreement with their genetic locations on the mitochondrial genome . An analysis of the corresponding amino-acid substitutions is also presented in the context of protein-antibiotic interactions.

Hosp Formul, 1988 Dec, 23 Suppl D, 32 - 5
An approach to cost-effective antibiotic utilization; Venezio FR et al.; For the past several years, the P & T Committee at the Loyola University Medical Center has conducted an extensive, ongoing review of antibiotic utilization . The program has led to the development of more specific drug use guidelines and tighter formulary control, which in turn has resulted in considerable cost savings to the institution . Drugs evaluated to date include vancomycin, antipseudomonal penicillins, aminoglycosides, and broader-spectrum beta-lactams, including the third-generation cephalosporins . A discussion of the review procedures, along with a brief analysis of the therapeutic and cost-effectiveness of each phase of the program, is presented.

Can J Hosp Pharm, 1988 Dec, 41(6), 295 - 301, 307
Assessment of the need for a home intravenous antibiotic program; Lee K et al.; Home intravenous antibiotic programs (HIAP) have been in existence for more than 12 years . The feasibility of such a program at the UBC-HSCH was assessed . The health records of all patients discharged between April 1, 1985 to March 31, 1987 with a diagnosis of septic arthritis, osteomyelitis, pyelonephritis, skin and soft tissue infections in the diabetic, prostatitis or infective endocarditis were reviewed retrospectively . Selection criteria to determine eligibility of patients for a HIAP were derived from the literature and grouped into three areas: patient, disease, and treatment criteria . From a total of 184 patients identified, 14 diabetic patients were excluded . The exclusion of patients with hospital stays of less than five days or those that did not have the appropriate diagnosis resulted in 77 patients available for more extensive review . Sixteen of 77 patients (20.8%) were judged eligible for a HIAP: 1 of 22 with pyelonephritis; 4 of 12 with septic arthritis; 5 of 21 with prostatitis; 2 of 12 with infective endocarditis; 4 of 10 with osteomyelitis . A total of 81 hospital bed days ($20,250.00) might have been saved if a HIAP was in place.

Antibiot Khimioter, 1988 Nov, 33(11), 838 - 42
{Effect of antibiotics on indices of immunologic reactivity in mice}; Artsimovich NG et al.; The effect of ristomycin, chloramphenicol, kanamycin, benzylpenicillin, streptomycin, and cephaloridine on the indices of cellular and humoral immunity was studied comparatively on intact animals and on animals with secondary immune deficiency . The study of the antibiotic effect on the count of rosette-forming lymphocytes (RFL) and the total count of lymphocytes showed that all the antibiotics except streptomycin induced a significant decrease in the count of RFL . The most active was kanamycin . It lowered the count of RFL 5-fold as compared to the control . The total count of lymphocytes was lowered after administration of ristomycin, chloramphenicol and kanamycin . In the animals with immune deficiency induced by cyclophosphamide benzylpenicillin potentiated the inhibitory effect of cyclophosphamide on the weight of the lymphoid organs, while streptomycin lowered the effect of cyclophosphamide . No such effect was observed with the use of the other antibiotics . The data indicated the necessity of taking into account the effect of various antibiotics on the immune system, especially under conditions of immune deficiency.

Antibiot Khimioter, 1988 Nov, 33(11), 806 - 10
{Coefficients of distribution of cyclic polyether macrotetrolide antibiotics between hydrophobic and hydrophilic solvents}; Sverdlova AN et al.; Dependence of distribution of 14C-macrotetrolide antibiotics between water and chloroform on the presence of various additives in the aqueous phase was studied with the radioindicator procedure . It was shown that in comparison to distilled water aqueous solutions of chlorine salts of ammonium, potassium and sodium increased the content of macrotetrolides in chloroform as a result of forming strong hydrophobic complexes . This is especially applied to the ions of ammonium whose addition to the aqueous phase led to an increase of macrotetrolide level in chloroform up to 98.4 per cent . Addition of weak hydrochloric acid or alkaline agents resulted in marked transfer of the ionophores into the aqueous phase at the expense of hydrolysis of the antibiotic cyclic molecules . The highest hydrolysis levels were induced by potassium hydroxide, the content of the ionophores in the hydrophobic phase decreasing up to 90.6 per cent . The effect of picric acid on distribution of the macrotetrolides between water and chloroform was different and depended on its concentration.

Am J Hosp Pharm, 1988 Nov, 45(11), 2341 - 5
Cost analysis of a home intravenous antibiotic program; Chamberlain TM et al.; A cost analysis of a home intravenous antibiotic program was performed, and the feasibility of the program was evaluated . All fiscal data related to the antibiotic therapy of the 10 study patients were collected from the patients' billing records and charts . Inpatient charges for antibiotics, supplies, laboratory tests, and the hospital room were identified from the patient's bill . Personnel costs were obtained from a log maintained by the home antibiotic team members . Charges accrued were converted to costs using the cost-to-charge ratio for each cost center . Fiscal analysis was performed using a subgroup of six patients with osteomyelitis . For all the patients, the mean duration of home therapy was 26 days . Inpatient treatment averaged 15.9 days . No major catheter-related problems were identified . For the osteomyelitis patients, the total cost of therapy, both inpatient and outpatient, was $57,854 . If all of the therapy for this subgroup of patients had been provided on an inpatient basis, the total cost would have been $98,314 . The home intravenous antibiotic program was determined to be feasible and cost-effective.

Methods Find Exp Clin Pharmacol, 1988 Nov, 10(11), 687 - 90
Interaction of aminoglycoside antibiotics and calcium channel blockers at the neuromuscular junctions; Paradelis AG et al.; Aminoglycoside antibiotics (mmol.l-1) gentamicin (0.74), streptomycin (1.02), netilmicin (1.24), amikacin (2.23), sisomicin (2.74), dactimicin (2.75), kanamycin (3.43), kanendomycin (3.45), tobramycin (3.53) and dibekacin (4.35) produce a complete neuromuscular blockade at the isolated phrenic nerve-hemidiaphragm preparation of the rat, which is only reversed by calcium chloride . On the other hand, verapamil (2.04 mmol.l-1), a calcium channel blocker, also produces a complete neuromuscular blockade at the above preparation which is reversed by calcium chloride . Aminoglycoside antibiotics are potentially capable of interacting with verapamil and produce a complete neuromuscular blockade at concentrations significantly reduced . The neuromuscular blockade which is produced by the concurrent administration of the aminoglycoside antibiotics and verapamil is obtained with the usual therapeutic blood concentrations of the individual agents . Furthermore, the neuromuscular blockade which is produced during verapamil-aminoglycoside antibiotics interactions is completely reversed after calcium chloride administration . The mechanism by which aminoglycoside antibiotics and verapamil produce neuromuscular blockade must be the same . Both classes of drugs interfere with calcium ions movements through the calcium channels of the membrane of the motor nerve-endings inhibiting acetylcholine release at the synaptic cleft . The interaction of aminoglycoside antibiotics and calcium channel blockers is of clinical significance because when these agents are given concurrently during the perioperative period they may lead to respiratory depression or prolonged apnoea . These respiratory disturbances can be managed by slow intravenous infusion of 50 to 200 mg of calcium gluconate.

Anticancer Res, 1988 Nov-Dec, 8(6), 1381 - 5
Preclinical pharmacokinetics of the antitumor antibiotic deshydroxy-sparsomycin in beagle dogs; Zylicz Z et al.; Sparsomycin (Sm) is a well known inhibitor of protein synthesis with anticancer potential . In order to minimize toxicity of this drug and increase its activity, several analogues were synthesized . Deshydroxy-Sm (dSm) appeared to be a good candidate for further investigations because of its lower toxicity and significantly higher antitumor activity in several ascitic tumors in mice . Pharmacokinetic evaluation in beagle dogs was performed using either single iv bolus or continuous infusion administrations . The drug was eliminated with a terminal t1/2 beta of 0.8 +/- 0.08 hours (48 +/- 5 minutes) . The mean volume of distribution was 0.4 +/- 0.06 l.kg-1 . The mean total body clearance was 6.4 +/- 0.8 ml.min-1.kg-1 . The drug is eliminated mainly by the kidneys (54%) . Active tubular secretion and active tubular reabsorption of the drug were observed . The pharmacokinetics was linear until the lethal dose . The results of this study provided additional data useful in selection of potentially useful analogues for further preclinical studies.

Jpn J Antibiot, 1988 Nov, 41(11), 1635 - 49
{A clinical trial of astromicin, a new aminoglycoside antibiotic, in thoracotomized patients and astromicin concentrations in the lung tissue}; Imaizumi M et al.; There have been no report on concentrations in human lung tissue of aminoglycoside antibiotics which are frequently used in combination with cephem antibiotics in the treatment of severe respiratory infections . The authors examined lung tissue concentration of astromicin (ASTM) during clinical trials in thoracotomized patients using intravenous drip infusion just before operation . And the following conclusions have been obtained: 1 . The average peak serum level obtained upon intravenous drip infusion of ASTM 200 mg for 1 hour just before operation was 11.2 micrograms/ml at 1 hour after starting the administration and half-life of ASTM in beta phase was 2.90 hours . 2 . ASTM concentrations in the lung tissue upon 1 hour intravenous drip infusion just before operation at a dose level of 200 mg reached a maximum at 2 hours after the start of the administration averaging 7.7 micrograms/ml and were 27.7-68.8% of serum peak level . 3 . Bronchiolar concentrations of ASTM 200 mg upon 1 hour intravenous drip infusion just before operation were 33.0-72.3% of peak serum level . These concentrations appear to be sufficient for the treatment of target infections . 4 . The 1 hour intravenous drip infusion of ASTM 200 mg appeared to be clinically safety and useful as was the intramuscular injection of ASTM 200 mg.

J Antimicrob Chemother, 1988 Nov, 22(5), 759 - 63
Response rates to a staged antibiotic regimen in febrile neutropenic patients; Barnes RA et al.; In a prospective study of 50 patients with prolonged neutropenia, we observed a 75% response rate to a staged empirical antibiotic regimen used to treat 101 episodes of fever . Additions or modifications to the protocol were rarely necessary . The use of an approach such as this improves the management of febrile neutropenic patients.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1659 - 67
Studies on the biosynthesis of the antibiotic crisamicin A and carbon-13 magnetic resonance assignments; Nelson RA et al.; The biosynthesis of crisamicin A, a novel dimeric isochromanequinone antibiotic from Micromonospora purpureochromogenes subsp . halotolerans has been investigated by {1-13C} and {2-13C} labeled acetate precursor feeding experiments . Analysis of the proton noise decoupled and off resonance 13C NMR spectra of 13C enriched and unenriched crisamicin A and their acetate derivatives indicated the biosynthesis via the polyketide pathway, as expected . Further analysis of the enriched spectra allowed the complete assignment of the carbon signals . Of particular interest was the establishment of the linkage between the two monomeric halves of the molecule and determination of the location of the phenolic hydroxyls.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1649 - 58
Biosynthesis of the macrolide antibiotic patulolides by Penicillium urticae S11R59: identification of the origin of carbon atoms by 13C NMR spectroscopy; Rodphaya D et al.; Patulolides are 12-membered macrolides produced by Penicillium urticae S11R59, and they are the simplest macrolide antibiotics . All carbon signals, including six methylene signals of patulolides A (1), B (2), and C (3), were completely assigned by use of the 13C two-dimensional INADEQUATE . The biosynthesis of patulolides was investigated with 13C labeled acetate . Feeding of {1-13C}acetate to a culture of P . urticae S11R59 gave patulolides A (1), B (2), C (3), each of which showed enrichment at carbons 1, 3, 5, 7, 9, and 11; enrichment at carbons 2, 4, 6, 8, 10, and 12 was observed upon feeding of {2-13C}acetate . These results showed that patulolides A (1), B (2), and C (3) are pure acetogenic hexaketides derived from six acetate units coupled in head-to-tail fashion.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1580 - 5
A new macromolecular antitumor antibiotic, C-1027 . II . Isolation and physico-chemical properties; Otani T et al.; A new macromolecular antibiotic C-1027 was obtained from the broth filtrate of Streptomyces globisporus C-1027 by precipitation with ammonium sulfate, DEAE-cellulose column chromatography and gel filtration chromatography on a Sephadex G-75 column . This antibiotic, prepared as a white powder, is an acidic polypeptide having an isoelectric point of pH 3.5-3.7 and a molecular weight of 15,000 as determined by SDS-polyacrylamide gel electrophoresis and gel filtration chromatography . The acid hydrolysate of the purified antibiotic C-1027 contained no methionine or tryptophan . From the physico-chemical data, it may be considered to possess a very labile non-protein chromophore.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1533 - 41
Novel antifungal antibiotics octacosamicins A and B . II . The structure elucidation using various NMR spectroscopic methods; Dobashi K et al.; The structures of octacosamicins A and B, two new antifungal antibiotics, were studied by spectrometries and chemical modifications . The 2D NMR techniques including 1H-detected heteronuclear multiple bond correlation method were successfully applied to this study . These antibiotics have unique linear chain structure possessing N-hydroxyguanidyl group at the terminal.

J Thorac Cardiovasc Surg, 1988 Nov, 96(5), 746 - 55
Cryopreserved and fresh antibiotic-sterilized valved aortic homograft conduits in a long-term sheep model . Hemodynamic, angiographic, and histologic comparisons; Jonas RA et al.; There is a paucity of clinical and experimental data regarding the fate of cryopreserved valve aortic homografts . Fifteen lambs (mean age 4 months) underwent insertion of a valved aortic homograft between the right ventricle and pulmonary artery . In eight animals, the homografts were treated with antibiotics for 48 hours followed by up to 4 days of 4 degrees C storage (group A) . In the other seven animals, the homografts were treated with antibiotics and cryopreserved at -196 degrees C (group B) . The 12 long-term survivors were catheterized at 6 weeks and 4 months after implantation, at which time three animals from each group were killed . The remaining six animals were catheterized and killed at 9 months . There was no significant difference in transconduit gradient (p = 0.67) or resistance indexed to weight (p = 0.81) between groups A and B . The mean increase in transconduit gradient for both groups between catheterization at 6 weeks and 4 months was 73%, and weight increased by 51% . Histologic analysis focusing particularly on valve leaflet architecture and changes in the aortic wall revealed greater differences between individual animals and according to duration of implantation than differences between groups A and B . However, focal intracuspal thrombus of unknown significance was seen only in animals from group B . Although conduit valve leaflets generally remained free of calcification, calcification was prominent within the conduit wall of all animals . In conclusion, cryopreservation does not appear to adversely affect leaflet integrity and conduit function in this accelerated animal model relative to fresh homografts . This is in contrast to past clinical experience with homografts treated by freeze-drying and irradiation.

J Assoc Off Anal Chem, 1988 Nov-Dec, 71(6), 1101 - 5
Electrophoretic methods for screening for antibiotics in animal feeds; Salvatore MJ Jr et al.; A new system for screening antibiotics in animal feeds involves washing antibiotic-containing animal feeds with a series of organic solvents to eliminate interferences and partially separate the antibiotics . Antibiotics are then determined by using paper electrophoresis and thin-layer bioautography . This approach enables the separation and qualitative identification of 17 antibiotics currently used in animal feeds and provides the ability to detect low-level cross-contamination.

Biochem J, 1988 Nov 1, 255(3), 937 - 41
Purification and characterization of pentagalloylglucose, and alpha-glucosidase inhibitor/antibiotic from the freshwater green alga Spirogyra varians; Cannell RJ et al.; An alpha-glucosidase inhibitor/antibiotic was purified from the freshwater green alga Spirogyra varians and was determined to be the pentagalloylglucose 3-O-digalloyl-1,2,6-trigalloylglucose.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1568 - 74
Thrazarine, a new antitumor antibiotic . II . Physico-chemical properties and structure determination; Takahashi A et al.; A new antitumor antibiotic thrazarine was soluble in water and positive to anisaldehyde-sulfuric acid and ninhydrin color reactions . The absolute structure of thrazarine was determined to be O-{3R)-2-diazo-3-hydroxybutyryl)-L-serine by acid hydrolysis, spectroscopic analysis and X-ray crystallographic analysis . Structurally, thrazarine was a new member of azaserine group antibiotics.

Genetika, 1988 Nov, 24(11), 1940 - 6
{Fusion of protoplasts in Streptomyces antibioticus}; Shevchenko AA et al.; The analysis of Streptomyces antibioticus recombinants isolated under non-selective conditions for stability of inheritance of parental properties demonstrated the existence of non-stable diploids and stable haploid recombinants . Also, genetic analysis of heteroclones isolated on selective medium after plating spores of regenerants was conducted . The results of analysis of haploid recombinant and heteroclones pointed to linkage of genetic loci and the possibility to use the technique of protoplast fusion for establishment of genetic map of S . antibioticus.

Br J Hosp Med, 1988 Nov, 40(5), 385 - 90
Clinicians' guide to antibiotics . Tetracycline; Pallett AP et al.; Tetracyclines have a broad range of activity against many organisms and remain the antibiotics of choice for some diseases, including brucellosis, chlamydial infections and severe acne vulgaris . However, because of their side effects, increasing resistance and the alternative antibiotics now available, their clinical usefulness is limited.

Rev Infect Dis, 1988 Nov-Dec, 10(6), 1163 - 70
Twelve-year review of recurrent native-valve infective endocarditis: a disease of the modern antibiotic era; Baddour LM; Recurrent cases of native-valve endocarditis have been seen for only the past four decades . In a review of the English-language literature over the past 12 years, 281 cases of recurrent infective endocarditis were found . Males were more than three times more commonly identified than females . Intravenous drug use was a designated risk factor for endocarditis in 43% of patients . Compared with patients with other risk factors for endocarditis, patients with intravenous drug use were significantly more likely (P less than .005) to suffer a recurrent bout of native-valve endocarditis within 12 months after the primary (or previous) episode . A greater variety of organisms were isolated from patients with recurrent endocarditis than from those with primary endocarditis . Valvular involvement was evenly distributed among the aortic, mitral, and tricuspid valves for both primary and recurrent episodes of infection . While complications of recurrent native-valve endocarditis were relatively common, the mortality rate associated with the recurrences was less than 30%.

Surgery, 1988 Nov, 104(5), 853 - 8
Factors involved in antibiotic selection in elective colon and rectal surgery; Coppa GF et al.; During a 24-month period, 350 patients were prospectively studied in an effort to determine the perioperative factors in the development of infections after colon and rectal resections . All patients received standard mechanical bowel preparation; perioperative parenteral cefoxitin (group A) or preoperative oral neomycin and erythromycin, in addition to perioperative cefoxitin (Group B), were also given . Both groups were comparable with respect to age, sex, associated diseases, and primary diagnosis . Wound infections developed in nine of 169 (5%) group B patients and in 15 of 141 (11%) group A patients . Stratification by type of operative procedure revealed that the rectal resections involved the highest rate of infection in group A (22%) and in group B (11%) . In patients requiring intraperitoneal colon resection, the rates of wound sepsis were similar (3% in both groups) . Analysis of length of operation revealed that in operations lasting 215 minutes or more the infection rate was 12%; in those lasting less than 215 minutes the rate was 4% . Patients with rectal resection and operative times of 215 minutes or more had a wound infection rate of 19% compared to 2% (p less than 0.05) in those with shorter nonrectal operations . Group B patients with the longer rectal operations had lower infection rates (11%) than group A patients (27%), while there was no difference among those who had shorter operations . Intra-abdominal abscesses (p less than 0.01) and anastomotic dehiscence (p less than 0.05) were also significantly reduced in group B patients . Postoperative wound infection is associated with length of operation and location of colon resection and can be significantly lowered by a combination of oral and parenteral antibiotics.

J Neurosurg, 1988 Nov, 69(5), 687 - 91
A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery; Bullock R et al.; In this study, 417 patients undergoing "clean" elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart . Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study . Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection . Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis--a statistically significant difference (p less than 0.05, Fisher's exact test) . Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.

J Biol Chem, 1988 Oct 25, 263(30), 15626 - 33
Two distinctive O-methyltransferases catalyzing penultimate and terminal reactions of macrolide antibiotic (tylosin) biosynthesis . Substrate specificity, enzyme inhibition, and kinetic mechanism; Kreuzman AJ et al.; S-Adenosyl-L-methionine:demethylmacrocin O-methyltransferase catalyzes the conversion of demethylmacrocin to macrocin as the penultimate step of tylosin biosynthesis in Streptomyces fradiae . The O-methyltransferase was purified to electrophoretic homogeneity by a conventional chromatographic procedure . The purified enzyme appears to be trimeric with a molecular weight of 122,000-126,000 and a subunit size of 42,000 . Its isoelectric point was 6.0 . The enzyme required Mg2+ for maximal activity and was catalytically optimal at pH 7.8-8.5 and 42 degrees C . The O-methyltransferase catalyzed conversion of demethylmacrocin to macrocin at a stoichiometric ratio of 1:1 . The O-methyltransferase also mediated conversion of demethyllactenocin----lactenocin . The corresponding Vmax/Km ratios for the two analogous conversions varied only slightly . Both enzymic conversions were susceptible to an extensive and identical range of metabolic inhibitions . Steady-state kinetic studies for initial velocity, substrate analogue, and product inhibitions are consistent with Ordered Bi Bi as the reaction mechanism of demethylmacrocin O-methyltransferase . Except for an identical kinetic mechanism, demethylmacrocin O-methyltransferase can be readily differentiated from macrocin O-methyltransferase by its physical and catalytic properties as well as metabolic inhibitions.

Surg Gynecol Obstet, 1988 Oct, 167(4), 315 - 8
Value of subcutaneous and intraperitoneal antibiotics in reducing infection in clean contaminated operations of the colon; Salvati EP et al.; A prospective study of 443 patients undergoing clean contaminated operations of the colon was undertaken to determine the efficacy of subcutaneous and intraperitoneal antibiotics in reducing infection . All of the patients received a mechanical intestinal preparation as well as preoperative antibiotics taken orally and preoperative and postoperative antibiotics administered intravenously . The over-all wound infection rate was 2 per cent . The routine additional use