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Mol Biol Rep, 1975 Jul, 2(2), 167 - 73
Interaction between membrane properties and proteins synthesis in reticulocytes - a two step inhibition of protein synthesis by valinomycin; Breitbart H et al.; In this work we consider the differential effect of Valinomycin used at different concentrations both on the protein synthesis of reticulocytes and on 42K exchange . We demonstrate that there is a two step action of this antibiotic . At 10(-6)M and below the drug has no effect on the 42K exchange, but it stops, however reversibly, protein synthesis . At 10(-5)M the drug has a very sharp action on the 42K exchange and stops protein synthesis in an irreversible way . Ribosomal population checked by two ways, sucrose gradient and direct counting on E.M . sections shows that at low concentrations of Valinomycin (10(-8)M to 10(-6)M) there is no breakdown of the polysomes which can be detected by either one of these methods . On the contrary, after short incubation with 10(-5)M of Valinomycin the breakdown of ribosomes is very clear, as evidenced by sucrose gradient analysis . By direct ribosomes clusters counting on E.M . sections this breakdown is seen only after long incubation.

Nucl Med (Stuttg), 1975 Jun 30, 14(2), 163 - 71
Labeled metronidazoles as potential new agents for amebic hepatic abscess imaging; Tubis M et al.; Two new radiopharmaceuticals were developed as possible agents for demonstrating the presence of hepatic amebic abscesses by selective accumulation of these agents in the abscess contents . These agents are: 131I-labeled Bromometronidazole, that has been shown to possess some of the antibiotic activity of metronidazole or Flagyl; and a Technetium 99m-penicillamine-Flagyl complex . A method of radioiodination has been devised which can be performed in radiopharmaceutical laboratories . Both radiopharmaceuticals are of very low toxicity . Distribution studies in animals show accumulation in the liver and elimination by way of the gallbladder . Scintillation camera studies depict a rapid uptake by the liver with subsequent biliary excretion . Animal models for the study of hepatic amebic abscesses are not available . A human patient with suspected amebic abscesses has been studied with negative findings that were confirmed at surgery . Collaborative studies are now in progress in several areas of the world where amebiases is endemic.

J Am Vet Med Assoc, 1975 Jun 15, 166(12), 1164 - 9
Treatment of discospondylitis in the dog; Gage ED; A combination of spinal cord decompression, spinal column immobilization, and systemic antibiotic therapy was used to treat discospondylitis in 30 dogs . Recovery was complete in 7 of 9 dogs with cervical involvement and in all 21 dogs with thoracolumbar involvement.

Z Hautkr, 1975 Jun 15, 50(12), 499 - 505
{Haloprogin . Its effects in the presence of glucocorticoids and neomycin}; Raab W et al.; The problem was studied whether the activity of haloprogin is decreased in the presence of glucocorticoids (6-methyl-prednisolone hemisuccinate sodium; hydrocortisone) or in the presence of a bacteriostatic antibiotic (neomycin) . Antifungal activity was determined by measuring changes in oxygen consumption of Saccharomyces cerevisiae in the resting phase . The results revealed that neither glucocorticoids in concentrations which activate yeast metabolism, nor neomycin impair the antifungal activity of haloprogin . Therefore, haloprogin may safely be used together with glucocorticoids and neomycin in topical therapy.

Sem Hop, 1975 Jun 14, 51(28), 1941 - 8
{Septicemic complications of venous perfusion catheterization . 4 years' experience in an intensive care unit}; Leclerc P et al.; Septicemia is a complication of prolonged venous catheterisation; although rare, is at present important owing to the severity of the condition and the possibility of prevention . The severity should lead one to very careful precautions to avoid sepsis, which antibiotic therapy and emergencies often lead one to neglect . The development of research on the prophylaxis of septicemia suggests that in the future, prolonged intravenous fluid may be given less dangerously . They are usually essential during the initial stages of intensive care.

Science, 1975 Jun 4, 189(4196), 51 - 3
Induced adhesion in Crassostrea virginica larvae; Ukeles R et al.; Normal motile veliger larvae of the oyster, Crassostrea virginica, were observed swimming in pairs or trios . Adhesion between animals is firm and has a specific orientation . This adhesion can be induced in low frequencies by culturing larvae at high densities, and in much higher frequencies by inclusion of an antibiotic mix in the seawater culture medium.

No Shinkei Geka, 1975 Jun, 3(6), 495 - 9
{False aneurysm due to mycotic angitis-case report (author's transl)}; Sakaki T et al.; Cerebral mycotic angitis takes place as a secondary disease to inflammation which is precipitated on the arterial wall to the artery, most frequently the vasa vasorum, as a result of settlement of infectious embolus into there, and it is usually seen in the patient with cardiac disease . The middle cerebral artery is a major region where the lesion takes place in multitude, and it is only rarely seen in the patient having infection in the brain or dura mater . We have recently experienced a very rare case in which false aneurysm was induced in the internal carotid artery by angitis due to Aspergillus, and this report deals with case . A 26-year-old office-man: He was attacked by loss of consciousness, aphesia, right hemiparesis during work in his office . As left CAG demonstrated evidence of arteriovenous malformation, redical operation was performed . He took a favorable course postoperatively, but developed meningitis on 10th day, when massive antibiotic therapy was started . During treatment, however, his consciousness rapidly decreased, and it was found on left CAG that there was false aneurysm in the cisternal segment of the left internal carotid artery which has previously been completely healthy . Operation was practiced once again to reinforce the wall of the left internal carotid artery, but the patient died of aggravated meningitis . Autopsy demonstrated a very fragile left internal carotidartery associated with perporation which was surrounded byprominent coagula . Histological examinations indicated that the perforation of the vascular wall had been caused by angitis due to Aspergillus infection.

Antibiotiki, 1975 Jun, 20(7), 649 - 52
{Chlorlincocin kinetics in animals with a disordered hormonal balance}; Dumova AM et al.; Distribution of chlorlincomycin in intact rats and animals with an impaired hormonal balance was studied . Estradiol or hydrocortizon acetate were administered repeatedly to the animals in large doses with a purpose of inducing pathological conditions . Chlorlincomycin was administered intravenously for 11 days in a dose of 15 mg/kg . The antibiotic levels in the blood serum and organs of the rats were determined at various intervals after the drug administration . The hormones induced changes in the sexual cycle . Hydrocortizon acetate markedly changed the animal weight and the weight coefficient of the internal organs . The kinetics of chlorlincomycin in the animals with hormonal impairments induced by estradiol or hydrocortizon acetate changed insufficiently as compared to that in the intact rats . Individual fluctuations in the antibiotic distribution was observed in the animals treated with hydrocortizon acetate . The levels of chlorlincomycin in the blood of the weakest animals were higher . No cumulation of the drug was noted.

Antibiotiki, 1975 Jun, 20(7), 658 - 64
{Study of the action of nystatin on the plasmatic membranes of the liver of rabbits}; Kravchenko LS et al.; The effect of mystatin on the plasmic membranes of the rabbit liver after intravenous administration of the antibiotic to the animals in a dose of 5 mg/kg was studied . It was found that intravenous administration of nystatin had no effect on the quantitative content of protein, lipids and nucleic acids in the plasmic membranes of the liver . The method of electrophoresis in polyacrylamide gel revealed significant changes in the composition of the liver membrane protein due to the treatment with nystatin . The effect of nystatin on the composition of lipids and fatty acids contained in the membrane lipids was also investigated . The data of the thin layer chromatography showed that nystatin did not affect the qualitative composition and the content of separate lipid fractions in the lipids of the liver plasmic membranes . However, the fatty acid analysis of the membrane lipids after intravenous administration of nystatin revealed a number of qualitative and quantitative differences in the composition of the lipid fatty acids of the membranes tested . The results showed that nystatin affected the membrane structures of the rabbit liver cells.

Antibiotiki, 1975 Jun, 20(7), 646 - 9
{Comparative study of the circulation of semisynthetic cephalosporins in the blood of rabbits}; Klimov VS et al.; Circulation of 4 semisynthetic cephalosporins, such as cephaloridin, cephalotin, cephradin and cephacetryl in the blood of rabbits after their intramuscular administration in single doses of 5 or 20 mg/kg was studied . The above antibiotics were satisfactorily absorbed into the blood reaching the maximum level within 15 to 30 minutes . The blood levels of cephalotin were the lowest and the rate of its elimination from the blood was higher than that of the other drugs . A four-fold increase in the doses of cephalosporins was not accompanied by a proportional increase in their levels in the rabbit blood, the time of the antibiotic circulation in the blood being not significantly changed.

Antibiotiki, 1975 Jun, 20(6), 494 - 6
{Acid-base properties and the thermodynamics of amphotericin B ionization in aqeous solutions}; Etingova NI et al.; Acid-base properties of amphotericin B, polyenic antibiotic in aqueous solutions was studied . A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of the water-insoluble substance . The ionization constants of the carboxylic and amine groups of the antibiotic were determined at several temperatures . It was found that ionization of the acid group did not depend on the temperature . At the same time the heat effect of the amine group ionization was significant and amounted to about 10 kcal/mole . Thermodynamic analysis of the ionization process of amphotericin B in aqueous solutions was performed . Integral components defining the process energetics were calculated.

Res Commun Chem Pathol Pharmacol, 1975 Jun, 11(2), 233 - 43
Comparative bioavailability of anhydrous griseofulvin and its chloroform solvate in man; Bates TR et al.; Using a crossover experimental design, the absorption profile of griseofulvin was assessed in human volunteers after oral administration of a 500 mg dose of the antifungal antibiotic as capsules of the anhydrous (nonsolvated)-and monochloroform solvate forms of the drug . The maximum body level of drug and the rate and extent of griseofulvin absorption (or bioavailability) were significantly increased after administration of the chloroform solvate as compared to that observed after administration of the nonsolvated form of the drug . The enhanced absorption of griseofulvin chloroformate correlated well with its enhanced solubility and dissolution rate at 37 degrees C in simulated intestinal fluid (20 mM sodium deoxycholate, pH 7.5) . This is the first demonstration of a drug-organic solvate displaying improved gastrointestinal absorption characteristics over the anhydrous form of a drug.

Jpn J Antibiot, 1975 Jun, 28(3), 335 - 40
{Clinical experience with ampicillin-cloxacillin (Rectocillin 'Kyowa') in uroloigcal field (author's transl)}; Nakano N et al.; Ampicillin-cloxacillin (Rectocillin 'Kyowa') was administered either orally (capsules) or by intravenous drip infusion to a total of 40 patients and the following results were obtained: 1 . Effectiveness obtained in the group received Rectocillin capsules (1,500 mg/day) was 80% . 2 . Effectiveness obtained in the group received Rectocillin intravenous drip infusion (3 similar to 10 g/day) was 64.7% . 3 . Side effects were encountered in 2 of 40 patients, but none of them were serious, and clinical abnormalities due to this antibiotic were not observed.

J Antibiot (Tokyo), 1975 Jun, 28(6), 434 - 41
I . Isolation and characterization of the transformation products of maridomycin III; Shibata M et al.; Three transformation products of maridomycin (MDM) III, a macrolide antibiotic, by Streptomyces lavendulae were isolated by silica gel and alumina chromatography, and designated as spots 1 (starting MDM III), 2, 3 and 4, in the order of their decreasing Rf values on thin-layer chromatogram . By mass- and NMR-spectrometry and thin-layer chromatography, spot 2 was identified as 18-dihydro-MDM III, spot 3 as 4''-depropionyl-MDM III, and spot 4 as 18-dihydro-4''-depropionyl-MDM III . The relationship between starting MDM III and these transformation products were also discussed.

Can J Microbiol, 1975 Jun, 21(6), 911 - 9
Streptomycin resistance in chloramphenicol-producing strains of Streptomyces species 3022a; Francis MM et al.; Resistance to low (5 mug/ml) concentrations of streptomycin in agar media was not inherited by all of the surviving population . Outgrowth of cultures in liquid media supplemented with the antibiotic depended upon inoculum size . Antibiotic titers in the supplemented cultures decreased during incubation, and an inactive radioactive product was detected when {14C} streptomycin was used . This low-level resistance is, therefore, attributed to enzymic inactivation of the antibiotic . Growth 10 mug/ml or higher concentrations of streptomycin on agar media was due to selection of resistant variants present in the parent strain . A range of such variants existed, decreasing in frequency as their degree of resistance increased . Examination of one that was resistant to moderate concentrations of streptomycin, (25 mug/ml) and a second that was resistant to high (100 mug/ml) concentrations of streptomycin suggested that both possed ribosomes which had lower affinity for the antibiotic than those of the parent strain, and that tolerance to high levels of streptomycin was due to a resistant ribosomal system for protein biosynthesis.

Thorax, 1975 Jun, 30(3), 266 - 70
Effect of preservation on the elasticity of human aortic valve homografts; Ng YL et al.; The elastic properties of preserved human aortic homografts after different storage times in antibiotic-nutrient medium solution have been measured . There was a definite loss of elasticity within nine months leading to a rapid decrease after a year of preservation . It is likely that satisfactory valve function depends on its elasticity, and these studies indicate that aortic valves which have been exposed to antibiotic media for more than nine months should not be used in valve replacement surgery.

Obstet Gynecol, 1975 Jun, 45(6), 609 - 13
Death from pseudomembranous enterocolitis; Ledger WJ et al.; During the past 2 years at the Los Angeles County-University of Southern California Medical Center (LAC-USC), there have been 2 deaths from pseudomembranous enterocolitis . Each of these deaths occurred postoperatively in previously healthy women who received pronlonged antibiotic prophylasix . The implications of these poor therapeutic results are discussed . The distinctive clinical symptology of a patient with pseudomembranous enterocolitis is described, and current treatment recommendiations are presented.

Clin Pharmacol Ther, 1975 Jun, 17(6), 692 - 700
Carbenicillin therapy in patients with normal and impaired renal function; Latos DL et al.; Optimun therapy with carbenicillin entails the use of high serum concentrations and the risk of significant dose-related toxicity . We report a study of serum clearance method of dose adjustment of carbenicillin patients with normal and imparied renal function . This method was found to provide serum concentrations considered to be satisfactory in every instance, by either constant-rate or intermittent infusion, and should enable greater precision in the use of the antibiotic . Implications of these findings aimed at providing dosage schedules for patients with renal failure are discussed.

Ann Surg, 1975 Jun, 181(6), 881 - 7
Cholangitis with acute renal failure: priorities in therapeutics; Bismuth H et al.; Obstructive cholangitis with acute renal failure is a dramatic syndrome which merits individual definition . Twenty-one patients with acute suppurative cholangitis complicated by rapidly developing renal insufficiency were studied, and the severity of the renal failure, an acute interstitial tubulopathy, bore no significant relationship to the serum bilirubin level . The mechanism of renal damage was clearly related to episodes of septicemia . Increasing experience has modified the approach to treatment . The dominant septic problem can often be controlled by vigorous antibiotic and fluid therapy, allowing time for spontaneous improvements in renal function . All patients thus operated at a distance from the septic episode survived . If emergency operation is required because of persistent or recrudescnet sepsis, the necessity for dialysis should be considered first; the circumstances demanding dialysis are defined . The priorities in therapy are then: 1) treatment of the infection, 2) treatment of the renal failure, and finally 3) operation . The amount of the operation depends on the evolution of the sepsis, but should be preceded by dialysis when required.

Arch Intern Med, 1975 Jun, 135(6), 850 - 2
Nephrotoxicity of combined cephalothin-gentamicin regimen; Cabanillas F et al.; Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy . Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity . High doses of this antibiotic combination should be avoided especially in elderly patients . Patients with renal insufficiency should not be given this regimen.

Arch Ophthalmol, 1975 Jun, 93(6), 429 - 31
Expandable silicone implants for scleral buckling . IV . Experiments with an explant for macular breaks; Huamonte F et al.; A new expandable silicone rubber explant used to indent the sclera at the macula was tested experimentally in rabbits . The device consists of a Dacron-reinforced silicone rubber strip that has an expandable portion (or balloon) at its midpoint connected to a silicone filling tube . The explant was expanded with 0.03 to 0.06 ml of an antibiotic solution . Smooth, round buckles that exerted even indentation were produced . A decrease in height of 20% to 50% was observed ophthalmoscopically during six months of follow-up . The degree of buckling can be easily controlled during operation and may be modified postoperatively.

Br J Vener Dis, 1975 Jun, 51(3), 210 - 12
Natamycin in genital candidosis in men; Masterton G et al.; In a trial of natamycin, an antifungal antibiotic in a vanishing cream base, assessment was possible in 66 men with genital or anal candidosis . The overall cure rate was 82 percent, In 43 patients with culturally proven candidosis it was 98 percent . but in 23 patients treated solely on clinical impression it was only 52 percent . Symptoms were rapidly relieved in those who responded and there were no side-effects . In our hands, natamycin 2 per cent cream has proved to be a valuable preparation in the treatment of candidal balanitis.

P N G Med J, 1975 Jun, 18(2), 113 - 8
Infections of the hand; Gray FJ; In this paper the importance is stressed of the dangers associated with neglecting hand infections in Paua New Guinea, where, for understandable reasons, there is a tendency for people to be slow in seeking treatment . The prevention of hand infections is emphasised, and the principles in regard to rest, antibiotic therapy, and surgical decompression are discussed . The more common types of hand infection are described, with particular reference to surgical anatomy and surgical drainage . Some of the more complicated infections such as middle palmar and thenar space infections, suppurative tenosynovitis, osteomyelitis and septic arthritis are of sufficient importance to warrant the attentions of the specialist surgeon when this is possible.

Proc Natl Acad Sci U S A, 1975 Jun, 72(6), 2170 - 4
Alamethicin-mediated fusion of lecithin vesicles; Lau AL et al.; It was recently shown that alamethicin greatly facilitates the fusion of small, sonicated, lecithin bilayer vesicles . In the present work the details of this fusion process have been followed by monitoring the inner and outer choline methyl signals separately by proton magnetic resonance spectroscopy . It is shown that during the alamethicine-induced fusion some of the antibiotic molecules become translocated from the extravesicular aqueous medium into the enclosed intravesicular space, and these alamethicine molecules were found to affect the choline methyl signals from the inner half of the bilayer only . No evidence was obtained for transmembrane coupling of the two halves of the bilayer in the presence of alamethicin or for any effects that might be construed as due to incorporation of alamethicin molecules into the hydrophobic core of the bilayer.

Antibiotiki, 1975 Jun, 20(6), 529 - 32
{Comparative study of the antibiograms as well as serotype and virulence of Ps . aeruginosa cultures}; Sobolev VR et al.; Seven antibiotics, such as gentamycin, kanamycin, streptomycin, polymyxin M, carbenicillin, tetracycline and rifampicin were studied with respect to their effect on 260 strains of Ps . aeruginosa isolated from various sources within 1945-1971 . Gentamycin and polymyxin M proved to be most active in vitro . Carbenicillin showed moderate activity . The sensitivity levels of the cultures of Ps . aeruginosa isolated from various sources within 30 years were identical . Serological typing of 59 cultures of Ps . aeruginosa was performed and their virulence was studied in parallel with their antibiotic sensitivity testing . No correlation between the antibiograms, serotypes and virulence of Ps . aeruginosa was found.

J Clin Pathol, 1975 Jun, 28(6), 453 - 6
A study of the agglutinin response in 40 cases of bacterial pneumonia; Nicholls AC et al.; Comparison of the results of cultures from blood and sputum with those of agglutinin response in 40 cases of bacterial pneumonia and 36 controls suggests that a provisional identification of causal bacteria, for purposes of antibiotic therapy, may be made by the serological tests with much greater rapidity and comparable accuracy . A combination of these methods is recommended.

Am J Cardiol, 1975 Jun, 35(6), 866 - 71
Tissue valves; Wallace RB; The search for an ideal replacement for diseased intracardiac valves has resulted in the use of many tissue valves, including homografts, heterografts and valves of autologous and heterologous fascia lata and of pericardium . Operative mortality in experienced hands has been comparable to that of other operations using prosthetic valves . Sterilization and preservation techniques probably render the graft nonviable in all instances . Although early function has been satisfactory, late deterioration of leaflet tissue has led to valve failure in a high percentage of cases . At present, glutaraldehyde-prepared heterografts and fresh antibiotic-sterilized homografts appear to have the longest durability of the various tissue grafts used for valve replacement . The primary advantage of tissue valves has been the essential elimination of thromboembolic complications, and the primary problems have been infectious endocarditis and late graft deterioration.

Exp Hematol, 1975 Jun, 3(3), 197 - 204
Evaluation of biologic activity of ferric chloride-treated endotoxin in mice; Galley CB et al.; Endotoxin (lipopolysaccharide, LPS) treated with ferric chloride was tested for its potential as a non-toxic agent for enhancement of non-specific host resistance . A 1 mg dose of untreated endotoxin, injected i.p . into mice, resulted in 100 per cent mortality, whereas the same amount of chemically-treated endotoxin resulted in less than 35 per cent lethality . The radio-protective potential of the treated endotoxin was similar to that of untreated endotoxin, as 70 per cent of each group of mice tested with either substance survived a dose of 850 rad x-ray . Irradiated mice, challenged 8 days after 850 rad x-irradiation, died when injected with 25 mug of either untreated or treated endotoxin . Antibiotic decontamination of the intestinal tract of host animals reduced the possibility of toxicity from endogenous endotoxin after challenge . This treatment resulted in 100 per cent survival from a 25 mug challenge at 8 days post-irradiation . The ferric chloride-treated proved to be a more effective B-lymphocyte mitogen . At a dose of 100 mug, treated endotoxin resulted in a 50 per cent greater mitogenic stimulation of B-lymphocytes as compared with that found after exposure to untreated endotoxin . Several lines of evidence support the contention that tolerance to untreated endotoxin was induced by repeated injections of either endotoxin preparation 1) 100 per cent of all endotoxin-tolerant mice survived a 1 mg challenge dose of untreated endotoxin, 2) there was a reduced mitotic response of splenic B-lymphocytes after re-exposure with untreated endotoxin as compared with that observed for cells derived from saline-treated mice, and 3) all antibiotic decontaminated mice engrafted with spleen cells from mice made tolerant to either endotoxin preparation survive graft-versus-host disease . In conclusion, based on survival data from normal mice, ferric chloride-treated endotoxin is safer to use than normal endotoxin . Also, treated endotoxin can elicit biologic responses similar in magnitude to those found after injection of mice with untreated endotoxin.

Biochem Genet, 1975 Jun, 13(5-6), 283 - 300
Biochemical genetic studies of cycloheximide resistance in Neurospora crassa; Rothschild H et al.; Genetic analysis of a number of cycloheximide-resistant mutants of Neurospora crassa has shown that resistance is controlled by several genes . Two of these appear to be located on linkage group V . Resistance to the antibiotic is dominant in wild-type-mutant heterokaryons . Two types of cycloheximide-resistant mutants were isolated: one type exhibited colonial morphology only when grown in the presence of cycloheximide and the other type maintained normal morphology even at high concentrations of the antibiotic . Reconstitution experiments with supernatant solutions and 80S monosomes prepared from wild-type and resistant mutant strains indicated that the property of cycloheximide resistance most likely is associated with the ribosomes . No electrophoretic or serological differences were found between the ribosomal proteins of the wild-type and resistant mutants.

Antibiotiki, 1975 Jun, 20(7), 653 - 7
{Toxicological characteristics of ampicillin}; Khosid GM et al.; Toxocity of ampicillin trihydrate was studied in acute and chronic experiments . It was shown that the antibiotic had low acute toxicity, did not cumulate and had no skin-irritating effect . On its inhalation in concentrations of 5 mg/m3 for 4 months, ampicillin induced allergization of albino rats, decreased their immunity . The general toxic effect of the drug was slightly pronounced . Ampicillin in a concentration of 0.1 mg/m3 induced tension of the immunological reactivity of the organism . The maximum permissible concentration (MPC) of ampicillin in the working premises equal to 0.1 mg/m3 is recommended . Mark "Allergen" is necessary.

Antibiotiki, 1975 Jun, 20(7), 591 - 5
{Study of the effect of the oxytetracycline crystallization conditions on the process indices}; Lin'kov GI et al.; Such factors as the rate of the changes in pH, temperature, mixer speed and the nature of the anions present in the solution has a significant effect on the indices of oxytetracycline dihydrate crystallization, i . e . residual content of the antibiotic in the mother solution and the specific surface of the crystalls . In this connection the effect of the above factors on the main indices of the process were studied . On the basis of the experimental data dependences were found which provided determination of the crystallization conditions securing the process indices.

Schweiz Med Wochenschr, 1975 May 31, 105(22), 719 - 24
{Paget's deforming osteodysttophy}; Cottier P et al.; The present clinical aspects of Paget's osteodystrophy are reviewed . The nosological definition, localiztion, natural course and signs are described and the recent description of "rheumatoid manifestations" in Paget's disease by FRANCK et al . is mentioned . The same authors revealed a positive correlation between the grade of extenstion of Paget's disease in the whole skeleton and the concentration values for alkaline phosphatase and uric acid in the serum . Among the complications of Paget's disease the orthopedic, neurological, haemodynamic, oncologic, hematological and dermatological are reviewed X-ray of the involved skeleton, which in most cases is diagnostic, may be supported by isotope scanning with 18F or 87mSr and bone biopsy for establishment of diagnosis . Current drug therapy is confined to diphosphonate and calcitonin . The antibiotic mithramycin, which is cytotoxic, reduces bone turnover and may improve the course in Paget's disease . However, toxic side effects on kidney, liver and hemopoiesis do not allow its further therapeutic use in this disease . A case is described which demonstrates that a spontaneous or traumatic fracture in the area of osteodystrophy exhibits almost the same potential for conso lidation as normal bone tissue following both conservative and osteosynthetic treatment of the fracture . In a further instance corrective osteotomy with osteosynthesis (plate) because of serious varisation and antecurvature of the femur due to Paget's disease were performed sucessfully without assisting drug therapy . A third patient displayed extensive osteodystrophy of the whole pelvic skeleton, which was discovered by X-ray as rehabilitation following CVA failed to progress due to severe bilateral reduction of hip joint function . In view of the age and general status of the patient and the absence of pain, no medication or surgical therapy was performed in this case.

J Biol Chem, 1975 May 25, 250(10), 3655 - 9
Identification of a chloroplast ribosomal protein altered by a chloroplast mutation in Chlamydomonas; Ohta N et al.; Direct evidence is presented that a chloroplast gene mutation in Chlamydomonas reinhardi alters one of the chloroplast ribosomal proteins . Proteins of 30 S subunits of chloroplast ribosomes from mutant strains, carrying maternally inherited antibiotic resistances, were compared with those from the wild type strain by CM-cellulose column chromatography and gel electrophoresis . When 30 S ribosomal proteins from a {3H}arginine-labeled streptomycin-resistant strain and a {14C}arginine-labeled wild type strain, or vice versa, were cochromatographed on a CM-cellulose column, one peak (Peak 17) was absent from the mutant profile . Instead, a pronounced peak was observed to elute at a slightly lower ionic strength than Peak 17 in the region of Peak 16 . The molecular weights in both Peak 16 and Peak 17 regions determined by discontinuous sodium dodecyl sulfate polyacrylamide gel electrophoresis were indistinguishable, approximately 18,000 . Thus, a chloroplast gene mutation to streptomycin resistance has altered the chromatographic behavior of a chloroplast ribosomal protein of the 30 S subunit . We interpret the additional protein in the mutant eluting at Peak 16 as most likely the mutationally altered form of the Peak 17 protein.

J Biol Chem, 1975 May 25, 250(10), 3666 - 71
Deoxycytidine transport in the presence of a cytidine deaminase inhibitor and the transport of uracil in Escherichia coli B; von Dippe PJ et al.; Tetrahydrouridine, a cytidine deaminase inhibitor, prevents periplasmic degradation of deoxycytidine by Escherichia coli B . It does not inhibit deoxycytidine transport and therefore allows an accurate determination of deoxycytidine transport . Data obtained using tetrahydrouridine show that deoxycytidine is transported in E . coli B as the intact nucleoside by an active transport process, with a K-m of 6 times 10-minus 6 M . Cytidine and deoxyadenosine inhibit transport competitively, whereas guanosine has no effect on transport . Arsenate or KCN greatly reduces transport . In a mutant resistant to the nucleoside antibiotic, showdomycin, the active transport of deoxycytidine is lost, and residual slow uptake occurs by passive diffusion . Uracil is accumulated in E . coli B by an active transport process with a K-m of 5 times 10-minus 7 M.

Biochemistry, 1975 May 20, 14(10), 2051 - 7
The action of colicin E2 on supercoiled lambda DNA . I . Experiments in vivo; Saxe LS; A lambda DNA supercoil system has been developed to study the effects of colicin E2 on DNA in vivo . Colicin E2, a protein antibiotic synthesized by strains of coliform bacteria that carry the Col E2 plasmid, had as its most conspicious effect damage to the DNA of sensitive strains . Colicine E2 attacks the supercoiled molecul formed by labeled lambda DNA in superinfected cells as well as it attacks the bacterial DNA . The rate and extent of acid solubilization of the lambda supercoils and of host bacterial DNA induced by E2 treatment are nearly identical . Treatment of superinfected cells with colicin E2 results in the progressive conversion of lambda DNA supercoils to open circles and/or linear full lenght molecules, and subsequently to fragments less than full lambda in size . The first endonucleolytic reactions are single-strand and or double-strand breaks . The rate of supercoil breakdown as well as the final percent supercoils remaining unconverted, the size of the final lambda fragments, and the extent of solubilization are dependent on the multiplicity of colicin used . Additions of trypsin to E2-treated superinfected cells results in a cessation of further breakdown of the lambda molecules, presumably as a result of digestion of accessible colicin molecules . Energy is essential for an early event in colicin E2 action . The host enzymes, endonuclease I and Rec BC, may be instrumental in the nucleolytic process caused by colicin E2: endonuclease I in reaction preceding cell killing and Rec BC in a secondary degradation of the bacterial DNA.

Biochemistry, 1975 May 20, 14(10), 2138 - 45
Stopped-flow kinetic studies of actinomycin binding to DNAs; Bittman R et al.; Stopped-flow kinetic studies of the association of actinomycins with narural and synthetic DNA duplexes are presented . The actinomycins examined were D (C1), D lactam (in which the pentapeptide rings are closed by lactam instead of lactone linkages), X2, XObeta, and actinomine . The DNAs used included claf-thymus DNA, PM2, DNA, and two synthetic d(A-T)-lide copolymers containing 2,6-diaminopurine (DAP) in place of adenine residues, poly{d(DAP-T)}-poly{d(DAP-T)} and poly{d(DAP-A-T}-poly{d(DAP-A-T)} . Apparent equilibrium constants indicate that the DAP-containing polynucleotides bind actinomycin strongly . Comples formation of actinomycins D, D lactam, X2 and XObeta with these DNAs can be deconvoluted into five rate processes . These steps do not necessarily proceed to completion . The rates of two of these steps display a firstorder dependence on DNA concentration . The large negative entropies of activation of these steps suggest a high degree of restriction to freedom of motion on the respective transition states . The rates of the remaining three steps are independent of DNA concentration . Kinetic parameters of actinimycin binding to DNAs are presented and suggestions are made about some of the molecular evente believed to be responsible for the appearance of the five rate processes . For example, for DNA, poly{d(DAP-A-T)}, and poly{d(DAP-T)}, the observed order of apparent second-order rate constants, normalized to the concentration of actinomycin binding sites, suggests that binding of the antibiotic occurs most rapidly at binding sites (G-C of d DAT-T) near d(A-T) base pairs, where weakening of the double-helical conformation requires the least energy . Results obtained from studies of actinomycin D binding to heat-denatured poly{d(DAP-A-T)} and of actinomine and actinomycin D lactam binding to DNA suggest that the slow rate processes are related to an actinomycyl-pentapeptide-induced unwinding of the sugar-phosphate backbone of DNA accompanying insertion of the cyclic peptides into DNA.

Ann Thorac Surg, 1975 May, 19(5), 585 - 8
Balanced drainage of the contaminated pneumonectomy space; Miller JI et al.; The patient who needs a pneumonectomy but has an infected pleural cavity faces the probability of an empyema of the pneumonectomy space . Balanced drainage of a contaminated space may avoid this very serious complication . A patient with obstructing bronchogenic carcinoma associated with distal parenchymal suppuration and empyema is discussed . A pneumonectomy with balanced drainage of the pleural space was performed . After three weeks the mediastinum was stable, and daily irrigation of the space with antibiotic solution was begun . Following foourteen days of irrigation, the cavity was filled with antibiotic solution and closed . Follow-up has shown no subsequent space problems or infection . Balanced drainage is a useful method of dealing with a contaminated pneumonectomy space.

Cancer Res, 1975 May, 35(5), 1218 - 24
Antipyretic effect of cycloheximide, and inhibitor of protein synthesis, in patients with Hodgkin's disease or other malignant neoplasms; Young CW et al.; Infusion of cycloheximide i.v., an antibiotic known to inhibit synthesis of protein, at a rate of 0.2 mg/kg/hr, reliably caused lysis of fever in 15 chronically febrile patients with Hodgkin's disease who did not have detectable bacterial, fungal, or viral infection . Antipyretic effects were also seen in some patients with reticulum cell sarcoma, lymphosarcoma, acute leukemia, histiocytic medullary reticulosis, plasma cell myeloma, carcinoma of the lung, and carcinoma of the cervix . The drug failed to produce defervescence in four patients with normal granulocyte reserves, who were febrile due to bacterial infection . When infused at a rate of 0.2 mg/kg/hr, the drug apparently caused an acute alteration of protein metabolism in man in that plasma amino acid nitrogen rose acutely while plasma levels of muramidase and ribonuclease fell during the period of the infusion . The data suggest that continuing synthesis of protein may be involved in nonbacterial fever of neoplastic disease . Mammalian granulocytes and monocytes are known to elaborate a pyrogenic protein following appropriate stimulation; it is suggested that in some types of neoplastic disease, particularly Hodgkin's disease, tumor cells may produce and release a pyrogenic protein and that drug-induced inhibition of its synthesis is responsible for the observed lysis of fever.

Antibiotiki, 1975 May, 20(5), 433 - 7
{Effect of amphotericin B and its combination with 5-fluorouracil on the development of transplantable rat lymphosarcoma}; Iaremenko KV et al.; The studies were carried out on rats with subcutaneously transplanted metastizing Pliss lymphosarcoma . The animals were treated with amphotericin B administered intravenously in complex with sodium desoxycholate in doses of 336 and 20 Units/kg for 7 days beginning from 24th hour after the tumor transplantation . The treatment resulted in a statistically reliable inhibition of the tumor metastasizing as compared to the control animals . When the animals with the tumors were subjected to combined therapy with 5-fluoruracyl and amphotericin B, the antitumor and antimetastatic effect of 5-fluoruracyl significantly increased . Determination of amphotericin B binding with the organ homogenates showed that the antibiotic bound with the homogenates or the organs of the rats with the tumors to a greater extent than with those of the intact animals . The levels of the antibiotics in the tumor metastases were higher than those in the primary tumors.

Antibiotiki, 1975 May, 20(5), 458 - 62
{Efficient use of a combination of ampicillin and chymotrypsin}; Butylina LV et al.; The effect of chimotripsin on the level and duration of the ampicillin concentration increase in rats, as well as the effect of the enzyme on the in vitro antibiotic detection in the blood serum and organ homogenates of the animals was studied . It was found that rational combined use of ampicillin and chimotripsin required the enzyme administration not later than 1 hour before the antibiotic injection . Chimotripsin provided increased ampicillin levels in the blood serum and liver of the rats for at least 5 hours and in the kidneys and lungs for at least 4 hours . The enzyme present in the rats for 2 hours had no effect on determination of ampicillin activity in vitro in the presence of the blood serum and organ homogenates of the animals.

Antibiotiki, 1975 May, 20(5), 429 - 33
{Study of the antiviral action of gentamicin}; Novokhatskii AS et al.; Experimental data on the effect of various concentrations of gentamycin on reproduction of VEE and Sindbis viruses in tissue culture are presented . It was found that gentamycin had no cytotoxic effect on the primary tripsinized chick embryon fibroblasts (CEF) when used in doses of 10, 20 or 30 mg/ml and only when used in a dose of 50 mg/ml it induced 50 percent destruction of the cell layer . Multiplication of the VEE and Sindbis viruses in the culture of CEF was inhibited in the presence of gentamycin by 1.5--3.5 lg PFU/ml . Two stages in the virus inhibiting effect of gentamycin were determined on the model of VEE, i . e . the stage of inhibition in the absence of visible damages of the cells and the stage associated with their destruction . The doses of gentamycin higher than 3 mg/ml inhibited in parallel the virus specific synthesis and synthesis of the cell proteins and nucleic acids . At the same time, when gentamycin was used in a dose of 10 mg/ml, no impairement of the cell viability was observed and the cell capacity to produce high titers of the model virus was reduced after incubation without the antibiotic for 24 hours . The antiviral activity of gentamycin were therefore determined by revers inhibition of the cell metabolic activity.

Antibiotiki, 1975 May, 20(5), 397 - 403
{Polymorphism of a culture of the chromomycin producer, Actinomyces aburaviensis var . verrucosus}; Vinogradova KA et al.; Polymorphism of the chromomycin-producing orgnaism Act . aburaviensis var . verrucosus 144--3 was studied . The stable variants differed in the morphologo-cultural properties, assimilation of the carbon sources, the component composition of the luminescence substances and the quantitative property of the antibiotic production . A substance with violet luminescence was found in the culture of varient I in addition to chromomycin . Similarity of the phenotypes observed in variants 1 and 2 when grown on complex organic media is explained by intensive chromomycin production by variant 1 on such media . Active colonies may be selected according to the colour due to chromomycin . Forms with an activity almost 4 times higher than that of the initial culture were found among the colonies of variant 2.

Antibiotiki, 1975 May, 20(5), 393 - 7
{Production of active mutants of a new species of rifamycin producer resistant to specific actinophage}; Lapchinskaia OA et al.; Selection of a phage-stable strain of a new species of the rifamycin-producing organism was carried out . The phage-stable mutants were selected with respect to the virulent phage 2739 isolated from a lysogenic culture of the rifamycin-producing organism . Spontaneous phage-stable mutants formed at a rate of 0.8 per cent . Most of them belonged to the morphological colony type with a decreased activity level . No shifts in variation with respect to the property of the antibiotic production were noted under the action of phage 2739 . 62 per cent of the phage-stable variants isolated from the secondary growth colonies after infection with the phage were lysogenic and liberated phage 2739 to the culture fluid . Induction of mutations with MNNG, UV and gamma(Co30) rays increased the frequency of the phage-stable mutanta by 1.5 times . Active phage-resistant mutants stable to the phage because of its adsorption and liberating no phage 2739 into liquid media during its cultivation were selected.

Antibiotiki, 1975 May, 20(5), 389 - 93
{New producer of carminomycin, Actinomycer cremeospinus sp . nov.}; Gauze GF et al.; An actinomycete strain No . 85 was isolated from a soil sample on media with bleomycin . It was described as a representative of a new species . Actinomyces cremeospinus sp . nov . An antibiotic substance identical with carminomycin, an antitumor antibiotic was isolated from the culture fluid of the strain.

Ukr Biokhim Zh, 1975 May-Jun, 47(3), 295 - 8
{Peculiarities of RNA synthesis in sections of rat liver tissues and cells of chicken embryos under conditions of protein synthesis inhibition}; Halkin AP et al.; Kinetics of radioactive predecessors incorporation into RNA and proteins of the rat liver and chicken embryos cells was studied as affected by different doses of cycloheximide . In both cases a definite dependence is established for changes in the specific radioactivity of nuclei and cytoplasm RNA on the antibiotic concentration: the doses of cycloheximide which cause an insignificant inhibition of protein biosynthesis do not evoke an increase in the intensity of RNA biosynthesis . Intermediate doses of cyclohemide in certain periods of incubation stimulate incorporation of 2-14C-orotic acid into RNA both in experiments with the tissue sections and with cell culture . A dependence is supposed to be between the intracellular bond of the changes in RNA biosynthesis on a degree of protein biosynthesis inhibition.

Zh Mikrobiol Epidemiol Immunobiol, 1975 May, (5), 29 - 33
{RNA biosynthesis in the microsomes of splenic cells during the inductive phase of the immunological response}; Perelygin NL et al.; RNA labeled with 3H-uridine was extracted from the microsomes of the spleen of the intact and antigen-stimulated mice . A study was made of the composition of this RNA by electrophoresis in polyacrylamide gel . Apart from rRNA, there were revealed in the microsome composition up to 10 RNA components in the mol wt range of from 0.4-10(5) to 7-10(5) dalton and 2 componnents - between 7-10(5) and 1.7-10(6) dalton . Incorporation of 3H-uridine into the rRNA was the maximal 24 hours after the administration of the antigen, whereas the RNA with the mol wt between 0.4-10(5) dalton remaining practically unchanged for a period of three days after the immunization . 3H-uridine incorporation into these RNA was resistant to the action of low antibiotic (actinomycin D) doses . Immunization was not accompanied by the appearance of new, by molecular weight, RNA components.

J Neurosurg, 1975 May, 42(5), 593 - 6
Cerebral mucormycosis following open head trauma . Case report; Ignelzi RJ et al.; The authors describe a case of human cerebral mucormycosis following open head trauma and craniotomy, and discuss possible roles of steroids and antibiotic therapy in its pathogenesis . They suggest that the common usage of prolonged broad-spectrum chemoprophylaxis in head trauma may require critical review.

J Exp Med, 1975 May 1, 141(5), 1101 - 13
Subcellular platelet factor VIII antigen and von Willebrand factor; Nachman RL et al.; Subcellular membrane and granule fractions derived from human platelets contain factor VIIII antigen and von Willebrand factor activity but not factor VII procoagulant activity . Circulating platelets constitute a significant reservoir of plasma factor VIII antigen, containing approximately 15% of the amount of factor VIII antigen present in platelet-poor plasma . The antibiotic ristocetin, which aggregates human platelets in the presence of von Willebrand factor, nonspecifically precipitates platelet membrane factor VIII antigen . Thus normal platelets contain surface-bound as well as internally stored von Willebrand factor, a protein synthesized by endothelial cells which is necessary for normal platelet function in vivo.

Mikrobiologiia, 1975 May-Jun, 44(3), 465 - 9
{Intrinsic luminescence and differentiation in Actinomyces lucensis--producer of etruscomycin}; Poltorak VA et al.; The luminescence of Actinomyces lucensis producing etruscomycin was found to be caused not by the antibiotic but by additional luminescent substances . No direct correlation has been established between the content of the luminescent substances and the intensity of the luminscence . The latter depends on the differentiation of the colonies, i.e . on the presence of a dark layer that screens the luminescence of the colonial mycelium and is localized under the aerial mycelium . The dark layer contains pigments of the melanin type.

J Neurol Neurosurg Psychiatry, 1975 May, 38(5), 429 - 35
Cerebellar abscess . A review of 47 cases; Shaw MD et al.; Forty-seven cases of cerebellar abscess have been reviewed, 93% of which were secondary to otogenic disease . There has been little change in the annual incidence during the period of time under review . The overall mortality was 41%, but with successive decades the mortality has increased . Three factors appear to be of importance in determining survival: the patient's ability to control his infection; reduction of the effect of the posterior fossa mass, preferably by complete excision of the abscess under antibiotic cover; and, in the case of otogenic abscess, an adequate radical mastoidectomy with bone removal to the site of attachment of the abscess to the dura mater.

Arch Ophthalmol, 1975 May, 93(5), 354 - 6
Expandable silicone implants for scleral buckling . III . Experiments in vivo; Huamonte F et al.; Experimental scleral buckling was obtained in rabbits by using expanded silicone rubber implants under scleral trap doors . Buckle heights ranged from 2.3 to 4mm after injection of 0.05 to 0.15 ml of fluid into the implants . Therate of decrease in buckle height followed up opthalmoscopically for five months, was found to be slow and continous and was caused mainly by loosening by the scleral flaps rather than by the diffusion of fluid from the implants . Implants expanded with chorampenicol solutions provided sustained release of the antibiotic in the area of the operation . This was confirmed in agar plantes by inhibition of the growth of Sarcina lutea around subimplant tissues and the expanded implants that were recovered post mortem . These implants provided an opportunity of modify the buckle height easily, either during the procedure or postoperatively.

Am J Gastroenterol, 1975 May, 63(5), 414 - 9
Barium peritonitis; Vieta JO et al.; A case of generalized peritonitis, secondary to a rupture of the rectosigmoid portion of the colon is presented . The surgical management is discussed, a basic part of which is the use of a Baker tube to splint the small intestine while adhesions form in a pattern along the tube, as a substitute method for a Nobel plication, to prevent chronic small intestinal obstruction . Extensive lavage of the peritoneal cavity should also be carried out . Energetic fluid replacement with careful monitoring of the fluid and electrolyte balance is essential before, during and after the surgical procedure . Adequate broad spectrum antibiotic coverage is important . We believe that the management of these cases should be by surgical intervention and institution of the above mentioned measures and not by expectant therapy and treatment of complications.

J Clin Pharmacol, 1975 May-Jun, 15(5-6), 401 - 4
Chloramphenicol-containing drugs . A report from Spain; Erill S et al.; The composition of 185 Spanish compounds containing chloramphenicol, along with the information supplied in ther package inserts, were studied . Only 11 of these compounds contained chloramphenicol alone, this antibiotic being associated with other chemotherapeutic agents and/or other drugs in the remainder . Indications listed in the leaflet largely went beyond the limits of the medically established uses of chloramphenicol, and information concerning side effects, contraindications, or precautions was scanty and in some instances even confusing . A change in the availability of drug combinations containing chloramphenicol and an improvement of the information accompanying them is urged.

Arch Surg, 1975 May, 110(5), 481 - 4
Drug-induced colitis mimicking an acute surgical condition of the abdomen; Tedesco FJ et al.; Pseudomembranous colitis secondary to antibiotic therapy has received increasing recognition . During a one-year period, eight of 42 patients with this entity had findings closely resembling an acute surgical condition of the abdomen manifested by fever, leukocytosis, and severe abdominal pain and tenderness . All eight patients received clindamycin and two were also given lincomycin hydrochloride monohydrate . Differentiation from an acute surgical condition of the abdomen was difficult until the characteristic findings of pseudomembranous colitis were noted on proctoscopic examination . Unnecessary celiotomy was averted in all patients . Seven of eight patients responded to discontinuation of the antibiotic and supportive measures; one required a diverting ileostomy . Drug-induced colitis must be an important consideration in any patient recently receiving antibiotics who develops fever, abdominal pain, and diarrhea.

Obstet Gynecol, 1975 May, 45(5), 574 - 8
Prophylactic use of tetracycline for first trimester abortions; Hodgson JE et al.; PIP: An evaluative study of the prophylactic use of tetracycline in 1st-trimester abortions is presented . 2 groups of 1000 patients received 1.5 gm of tetracycline hydrochloride, orally, 2-3 hours before the abortion procedure, followed by 500 mg every 6 hours for 4 days . 2 groups of 1000 patients served as controls . The patient population and operative conditions were relatively uniform . The total complication rates for the antibiotic groups were 3.4% and 2.9%, and 9.1% and 8.8% for the controls . 118 of the control group patients experienced major complications compared with 45 patients in the antibiotic group . The results tend to support the arguments for the use of antibiotics in managing high-risk surgical procedures .

Blood, 1975 May, 45(5), 621 - 9
Some factors affecting fibrinogen precipitation by ristocetin: ultrastructure of precipitates; Ts'ao C et al.; Fibrinogen in aqueous solution is precipitated by the antibiotic ristocetin . This reaction is inhibited by albumin and facilitated by low temperature . Resolubilized fibrinogen clots in the presence of thrombin . Ristocetin-precipitated fibrinogen takes the form of fibrils or clumps, composed of irregularly spaced, structure-less particles . The addition of ristocetin to washed platelets suspended in fibrinogen-containing media produces fibrinogen clumps in both the media and in the surface cannalicular system of the platelets . The changes in light transmission (aggregation curves) are due to both platelet aggregation and fibrinogen clumping . The role of the latter is confirmed by the observation that the addition of ristocetin to inert latex particles suspended in fibrinogen solution produces typical aggregation curves . This phenomenon is prevented by the addition of albumin to the media . We conclude that (1) if fibrinogen is present in any artificial system, albumin should be included in the media to prevent fibrinogen precipitation; and (2) statements about aggregation of any particulated materials by ristocetin should not be based solely on light-transmission changes, but should also include a description of the morphologic appearance.

Mikrobiologiia, 1975 May-Jun, 44(3), 400 - 3
{Effect of heliomycin on protein and nucleic acid synthesis in Escherichia coli}; Korolev PN et al.; Heliomycin at a concentration of 100 mcg/ml had almost no effect on the growth of Escherichia coli, which was inhibited only upon the combined action of heliomycin and ethanol that facilitated the penetration of the antibiotic into the cell . Heliomycin inhibited in these conditions the synthesis of RNA and had no effect on the synthesis of DNA in the three studied strains of E . coli . The synthesis of protein either was not inhibited by heliomycin at all or was inhibited only to a small extent.

J Bacteriol, 1975 May, 122(2), 347 - 51
Insertion of a minor protein into the outer membrane of Escherichia coli during inhibition of lipid synthesis; Randall LL; The antibiotic cerulenin, a specific inhibitor of fatty acid synthetase systems, was used to demonstrate that a minor protein component of the outer membrane of Escherichia coli, which serves as the receptor for the phage lambda, can be synthesized and inserted into the outer membrane during inhibition of lipid synthesis.

Proc Soc Exp Biol Med, 1975 May, 149(1), 299 - 301
Effect of hamycin on plasma cholesterol of rat; Dave CV et al.; Hamycin, a polyene antibiotic, when administered orally with food or by a cannula or administered intraperitoneally produced a dose-dependent hypocholesterolemic effect on normal albino rats . A 50% decrease occurred in serum cholesterol level at 25-50 mg/kg oral dose of hamycin . No further decrease occurred in serum cholesterol level with increase in the oral dosage . Decrease in the serum cholesterol occurring with 0.5-1.0 mg/kg, ip dose of the antibiotic was similar to that observed with oral hamycin and suggest that the effect was possibly mediated through mechanisms other than those involving prevention of absorption of cholesterol through the gastrointestinal tract.

Ann Surg, 1975 May, 181(5), 716 - 21
Giant horseshoe intra-abdominal abscess; Altemeier WA et al.; A study of 12 patients with giant horseshoe abscess of the abdominal and pelvic cavities seen at the Surgical Services of the University of Cincinnati Medical Center has emphasized the complexity and bizarre nature of these lesions . These infections represented a huge abscess or series of communicating abscesses extending from one subphrenic space along the corresponding paracolic gutter into the pelvis, up and along the opposite paracolic space, and into the other subphrenic space . Since these lesions occurred infrequently, they were often not recognized until they had become far advanced and had produced profound effects on the patients . The diagnosis was difficult and obscured by various factors including the postoperative state after laparotomy for complex diseases or serious injuries of the biliary tract, the genitourinary tract, or the alimentary tract . An important etiologic component of the formation of these giant abscesses was the continuing escape and collection of large volumes of fluid resulting from lesions of the biliary tract, postoperative hemorrhage, or an unrecognized large perforated peptic ulcer . Nine patients were treated successfully and 3 died . The many diagnostic and therapeutic problems presented by the patients with this interesting and complex lesion have emphasized the importance of earlier and more accurate diagnosis, early and adequate surgical drainage, intelligently applied antibiotic therapy and appropriate supportive treatment . Failure to recognize and drain effectively each of the component sections of this lesion led to continuing sepsis with prolonged morbidity, progressive debility, and death.

Br J Surg, 1975 May, 62(5), 404 - 6
Recognition of infection associated with intravenous catheters; Freeman R et al.; Four cases are described in which the patients suffered from bacteriaemia due to infected intravenous infusions . Although all the patients were pyrexial, the white cell count was normal in all 4 cases at diagnosis and the infusion site appeared innocent . Following removal of the intravenous catheter and the institution of antibiotic therapy in each case, neutrophilia and localizing signs developed . It is stressed that a normal white cell count and an innocent appearance at the infusion site do not exclude this complication of intravenous therapy . Possible reasons for this presentation for sepsis are discussed.

J Pharm Sci, 1975 May, 64(5), 873 - 5
Ultracentrifugal study of effect of sodium chloride on micelle size of fusidate sodium; Richard AJ; Apparent micellar molecular weights were determined with the antibiotic fusidate sodium by ultracentrifugation in varying counterion concentrations (Na+) . The effects of buffer salts, pH, sodium chloride concentration, and drug concentration were studied . The results strongly support the concept of the formation of primary micelles composed of five monomer units, followed by aggregation of the pentomers into larger micelles as salt concentration increases.

Eur J Biochem, 1975 May, 54(1), 117 - 26
The mitochondrial ATPase . Evidence for a single essential tyrosine residue; Ferguson SJ et al.; 1 . Evidence is presented which indicates that inactivation of the mitochondrial ATPase from bovine heart by the reagent 4-chloro-7-nitrobenzofurazan results from modification of one tyrosine residue per enzyme molecule . Activity can be restored by a variety of sulphydryl reagents . 2 . In sodium dodecyl sulphate, the nitrogenzofurazan group on tyrosine is transfered to newly exposed sulphydryl groups on the enzyme . 3 . The rate of transfer of the nitrobenzofurazan moiety from theenzyme to sulphydryl compounds is compared with that for transfer from the model compound N-acetyl-tyrosine-0(7-nitrobenzo-furazan) ethyl ester, the synthesis and properties of which are also described . 4 . The ligands ATP and ADP exert a protective effect on the rate of reaction between the mitochondrial ATPase and 4-chloro-7-nitrobenzofurazan . The variation in rate of this reaction with change in pH has also been examined and a pKa of 9.5 estimated for the tyrosine residue . 5 . The modification does not prevent substrate binding as judged by changes in the fluorescence of aurovertin, an antibiotic with specific affinity for mitochondiral ATPases . 6 . When the ATPase activity of submitochondrial particles is inhibited by 4-chloro-7-nitrobenzo-furazan, there is a parallel decrease in the extent of the energy-linked fluorescence enhancement of 1-anilino-naphthalene-8-sulphonate induced by ATP hydrolysis . Both ATPase activity and the fluorescence enhancement are restored by sluphydryl reagents.

Postgrad Med, 1975 May, 57(6), 95 - 7
Symposium . ENT for nonspecialists . External otitis; McDonald TJ et al.; Simple treatment usually suffices for the control of acute external otitis, This consists of meticulous cleaning of the ear canal and application of antibiotic-corticosteroid drops . Good local care of the ear can prevent both the chronic and the acute forms of external otitis . Malignant external otitis is an uncommon but lethal type that most often accompanies diabetes . If this condition is diagnosed, hospitalization and aggressive treatment are then a necessity.

Am Fam Physician, 1975 May, 11(5), 80 - 4
Complications of acute frontal sinusitis; Clairmont AA et al.; The bone separating the frontal sinus from the anterior cranial fossa and the orbit is often quite thin . This, plus the interrelated venous drainage system of these areas, forms the anatomic basis for serious orbital and intracranial complications that must be recognized early . These include orbital cellulitis and abscess, cavernous sinus thrombosis, subdural and brain abscess and meningitis . Early hospitalization for intravenous antibiotic therapy and, occasionally, emergency surgical drainage are required.

Biochemistry, 1975 Apr 22, 14(8), 1713 - 8
Some characteristics of and structural requirements for the interaction of 24,25-dihydrofusidic acid with ribosome - elongation factor g Complexes; Willie GR et al.; Fusidic acid inhibits polypeptide chain elongation by binding to the ribosome - elongation factor-G - GDP complex and thereby preventing its dissociation . The experiments reported here quantitate the interaction of the antibiotic {3H}-24,25-dihydrofusidic acid, an active analog of fusidic acid, with the ribosome - elongation factor-G - GDP comples . All components of the complex are essential for {3H}-24,25-dihydrofusidic acid binding . The stoichiometry of the interaction is ca . 1:1, and the Ka apparent, as determined by equilibrium dialysis, is 2.6 times 10-6 M-minus 1 . It is further shown that GTP and GDP are equally effective in forming complexes to which the antibiotic may bind, whereas GMP and beta,gamma-methyleneguanosine triphosphate will not form complexes to which the antibiotic may bind . In order to examine the structural basis of the mode of antibiotic action shown by fusidic acid, we have considered two activities of 21 structural analogs of this antibiotic: ability to bind to the aforementioned ternary complex and ability to stabilize this complex . The comparative binding capability of the analogs were extablished through competition experiments with {3H}-24,25-dihydrofusidic acid . The data obtained from these experiments can be summarized as follows . (1) The C17-20 double bond of fusidic acid appears to be critical for both binding and complex stabilization activities . (2) A carboxyl group in the vicinity of the C20 carbon is also essential for both activities . (3) Modifications of other functional groups in the molecule can lead to significantly decreased stabilization of the ternary ribosome complex and/or ability to compete with {3H}-24,25-dihydrofusidic acid for binding to the complex, but do not demonstrate absolute structural requirements for either activity.

Biochim Biophys Acta, 1975 Apr 21, 389(1), 126 - 36
Showdomycin, a nucleotide-site-directed inhibitor of (Na+ + K+)-ATPase; Tobin T et al.; Showdomycin {2-(beta-D-ribofuranosyl)maleimide} is a nucleoside antibiotic containing a maleimide ring and which is structurally related to uridine . Showdomycin inhibited rat brain (Na+ + K+)-ATPase irreversibly by an apparently bimolecular reaction with a rate constant of about 11.01-mol- minus 1-min- minus 1 . Micromolar concentrations of ATP protected against this inhibition but uridine triphosphate or uridine were much less effective . In the presence of K+, 100 MUM ATP was unable to protect against inhibition by showdomycin . These observations show that showdomycin inhibits (Na+ + K+)-ATPase by reacting with a specific chemical group or groups at the nucleotide-binding site on this enzyme . Inhibition by showdomycin appears to be more selective for this site than that due to tetrathionate or N-ethylmaleimide . Since tetrathionate is a specific reactant for sulfhydryl groups it appears likely that the reactive groups are sulfhydryl groups . The data thus show that showdomycin is a relatively selective nucleotide-site-directed inhibitor of (Na+ + K+)-ATPase and inhibiton is likely due to the reaction of showdomycin with sulfhydryl group(s) at the nucleotide-binding site on this enzyme.

S Afr Med J, 1975 Apr 19, 49(17), 718 - 20
Dogbite injuries in children; Chait LA et al.; An analysis of 50 children suffering from severe dogbites showed that the face was the anatomical site of predilection (75%(, and that the breed of dog most commonly involved was the Alsatian (German Shepherd) . Primary debridement and suture under general anaesthesia is the treatment of choice . Ampicillin has been shown to be the antibiotic giving the widest over-all prophylactic chemotherapeutic cover.

Am J Obstet Gynecol, 1975 Apr 15, 121(8), 1071 - 4
The safety of lincomycin in pregnancy; Mickal A et al.; The progeny of mothers treated with lincomycin during the first, second, or third trimester of their pregnancy were extensively evaluated at various periods extending to 7 years after birth . As compared to a control group (mothers not receiving lincomycin), the study group did not show any more developmental anomalies of the teeth, specific physical defects, general developmental anomalties, or late developing abnormalities in speech, emotional and mental make-up, or ability to adjust to schooling, than would occur in the normal population . The relationship to clindamycin, a closely related derivative, and to antibiotic therapy during pregnancy is discussed.

South Med J, 1975 Apr, 68(4), 413 - 4
Primary peritonitis in adults; Golden GT et al.; Infection within the peritoneal cavity without an identifiable source of contamination is rare . The diagnosis is one of exclusion, and can be made with certainty only after a thorough laparotomy . The response to antibiotic therapy is usually prompt and gratifying.

Br Med J, 1975 Apr 5, 2(5961), 12 - 4
Falciparum malaria semi-resistant to clindamycin; Hall AP et al.; Clindamycin, a semi-synthetic antibiotic of the lincomycin family, at a dose of 450 mg eight-hourly for three days in adults cured five out of 10 patients moderately ill with chloroquine-resistant falciparum malaria . Combination therapy with full-dose quinine and clindamycin for three days cured all four patients so treated who were followed up, and with half dosage three out of five patients were cured . Both combinations, however, caused upper gastrointestinal toxicity and appeared to potentiate both toxicity and possibly antimalarial efficacy . Colitis due to clindamycin was not observed . Sequential therapy was not toxic and could be useful in patients who have relapsed after more conventional treatment.

Biochim Biophys Acta, 1975 Apr 2, 383(4), 427 - 34
Simultaneous ribosomal resistance to trichodermin and anisomycin in Saccharomyces cerevisiae mutants; Jimenez A et al.; A spontaneous mutant of Saccharomyces cerevisiae resistant to trichodermin has been isolated . It displays cross resistance both in vivo and in vitro to a number of sesquiterpene antibiotics (fusarenon X, trichothecin and verrucarin A) and to the chemically unrelated antibiotic anisomycin . The mutation conferring resistance to anisomycin and trichodermin is expressed in the 60-S subunit of the yeast 80-S ribosome . Mutant ribosomes bind {-14C}trichodermin much less efficiently than wild type ribosomes, suggesting that resistance may be due, at least in part, to this property . However, both types of ribosomes bind {-3H} anisomycin equally . These results suggest that anisomycin and trichodermin have different binding sites on the 60-S subunit of eukaryotic ribosomes, even though previous results have shown that both antibiotics bind to mutually exclusive sites.

Vestn Khir Im I I Grek, 1975 Apr, 114(4), 73 - 5
{Pulmonary complications in acute hematogenic osteomyelitis in children}; Sultanbaev TZh; An analysis of treatment in 49 patients has demonstrated that pulmonary complications aggravate the course of the disease and not infrequently are causes of lethal issues . It is considered that an early removal of the primary purulent focus by means of trephination and transosseous perfusion with antibiotic solutions in an acute stage provides for the prophylaxis of pulmonary complications and reduces the mortality.

Arch Sci Med (Torino), 1975 Apr-Jun, 132(2), 79 - 82
{Use of methyl partricin suspension in the oral diseases due to Candida species}; Koranyi G et al.; The effect of a new polyene antibiotic prepared in an oral suspension (SPA methyl-partricin) was studied in 29 nurselings with thrush . The results are compared with those obtained in two uniform groups treated with nystatin and gentian violet respectively . The new substance proved more effective in each case . Local and general tolerance were excellent.

Antibiotiki, 1975 Apr, 20(4), 329 - 32
{Study of the structure of colonies of active and inactive Actinomyces parvullus variants using luminescence and scanning microscopy}; Zaslavskaia PL et al.; The colony structure of the active and inactive proactinomycete-like variants of Actinomyces parvullus producing actinomycin D was studied with luminescent and scanning microscopy . Clear differentiation of the colony profile was shown by the structure and functions of the mycelium layers . A zone of active synthesis and accumulation of the antibiotic was observed in the colonies of the active variant in the upper part of the substrate mycelium with reddish-yellow self luminescence in UV light and characteristic close hyphae "cemented" by the intracellular substance . Formations of the granule type were often noted on the hyphae of that layer . The layer of the aerial mycelium was loosely connected with the substrate mycelium and consisted of sporophores and spore chains partially broken into single spores . The colonies of the inactive proactinomycete-like variant had a slightly differentiated profile with a sponge-like structure, no zones of the antibiotic synthesis being found . The presence of the intracellular substance was observed in the upper part of the colony supersubstrate mycelium.

Antibiotiki, 1975 Apr, 20(4), 324 - 8
{Study of the carbohydrate content in the mycelia of an active strain producing oxytetracycline and in an inactive mutant}; Bryzgalova TE et al.; The content of carbohydrates in the mycelium of the active strain and inactive mutant of the oxytetracycline-producing organism under conditions favourable (starch medium) and unfavourable (glucose medium) for the antibiotic biosynthesis was studied . The mycelium of both organisms was fractionated and carbohydrate distribution according to the mycelium fractions and carbohydrate content in every fraction were investigated . No significant differences were observed between the active strain and inactive mutant with respect to the characteristics studied . The carbon source in the medium had the dominating effect on the chemical composition of the mycelium . The mycelium of both strains grown on the starch medium contained much more carbohydrates than that grown on the glucose medium . The carbohydrates of the mycelium grown on the starch medium were mainly found in fraction III and must be represented by polysaccharides.

Bull Los Angeles Neurol Soc, 1975 Apr, 40(2), 56 - 9
Ventricular perfusion for ventriculitis; Weiss MH et al.; A system of ventricular perfusion of appropriate antibiotic solutions in the management of neonatal ventriculitis is described . The technique of perfusion as well as considerations in the appropriate selection of antibiotics and perfusates is detailed . The procedure was successfully utilized in a consecutive series of nine children refractory to conventional modes of therapy.

J Gen Physiol, 1975 Apr, 65(4), 515 - 26
Pores formed in lipid bilayer membranes by nystatin, Differences in its one-sided and two-sided action; Marty A et al.; Nystatin and amphotericin B induce a cation-selective conductance when added to one side of a lipid bilayer membrane and an anion-selective conductance when added to both sides . The concentrations of antibiotic required for the one-sided action are comparable to those employed on plasma membranes and are considerably larger than those required for the two-sided action . We propose that the two-sided effect results from the formation of aqueous pores formed by the hydrogen bonding in the middle of the bilayer of two "half pores," whereas the one-sided effect results from the half pores alone . We discuss, in terms of the flexibility of bilayer structure and its thickness, how it is possible to have conducting half pores and "complete pores" in the same membrane . The role of sterol (cholesterol and ergosterol) in pore formation is also examined.

Acta Orthop Scand, 1975 Apr, 46(1), 38 - 51
Characterization of bone cements; de Wijn JR et al.; Properties of acrylic bone cements during and after curing were determined for three brands of bone cement . Curing time and consistency were chosen for the characterization of the handling and working behavior of these materials . The performance of bone cements after curing may be related amongst other things to the following properties: water resorption, solubility/disintegration, flexural modulus of elasticity, yield stress, proportional limit, flexural strength and impact strength . Methods to determine these handling and material properties are described . The influence of radiopacifying and antibiotic additives on these properties is evaluated as well as the influence of porosity on flexural strength and impact strength . The results indicate that considerable differences in the handling properties occur . The material properties of the three brands tested do not show marked differences . Radiopacifying and antibiotic additives appear to have a negative effect on material properties; the effect of porosity as it develops during curing under simulated clinical conditions is more pronounced.

Am J Dig Dis, 1975 Apr, 20(4), 295 - 7
Ampicillin-associated diarrhea--A prospective study; Tedesco FJ; A prospective study of 200 consecutive patients receiving ampicillin for various reasons revealed that bowel habits changed in 16% and diarrhea occurred in 4.5% . No case of pseudomembranous colitis was found . The incidence with which bowel habits changed increased with larger total doses of antibiotic . Oral and intravenous routes causedthe same incidence of altered bowel habits . This study provides a proper comparison group to place clindamycin-associated colitis in proper perspective.

J Cell Biol, 1975 Apr, 65(1), 103 - 11
Mitochondrial and cytoplasmic ribosomes and their activity in blood and culture form Trypanosoma brucei; Hanas J et al.; Ribosomes of Trypanosoma brucei, a parasitic, flagellated protozoan (order Kinetoplastida), were identified on sucrose density gradients by their radioactively labeled nascent peptides . Ultraviolet absorption revealed only cytoplasmic ribosomes which served as internal sedimentation markers . Synthesis on cytoplasmic ribosomes was completely inhibited by cycloheximide . In the presence of this antibiotic, nascent peptides were associated with ribosomes of lower sedimentation coefficient than the cytoplasmic ribosomes . Chloramphenicol blocked synthesis on these ribosomes which are probably the mitochondrial ribosomes . These ribosomes differed from the cytoplasmic ribosomes in several ways . Their sedimentation coefficient was about 72S rather than 84S . The stability of the 72S ribosomes was less sensitive to pancreatic ribonuclease and low Mg-++ concentrations, dissociating below 0.1 mM Mg++ . The 72S ribosomes were more sensitive to elevated KCl concentrations, dissociation above 0.25 M . Protein synthetic activity associated with the 72S class of ribosomes was found in trypanosomes grown in rats . Under these conditions no cytochromes or fully active Krebs cycle is present in these cells and respiration is insensitive to cyanide.

Can J Comp Med, 1975 Apr, 39(2), 216 - 23
A pharmacological study of chloramphenicol in horses; Sisodia CS et al.; Pharmacological disposition of chloramphenicol was studied in horses . Minimum levels of the antibiotic (greater than or equal to 5 mu g/ml) in blood or plasma recommended to combat infections could not be achieved by 4.4 and 8.8 mg/kg I.V . or 30 and 50 mg/kg I.M . or 30 mg/kg oral (as palmitate salt) doses of chloramphenicol . Increasing the dose to 19.8 and 26.4 mg/kg I.V . provided such levels for about two and three hours respectively . A combination of 20 mg/kg I.V . and 30 mg/kg I.M . administered simultaneously did not provide more prolonged levels than 26.4 mg/kg I.V . alone . Chloramphenicol succinate produced higher but not more prolonged levels in blood and plasma than those produced by pure chloramphenicol . Succinate salt is very little, if at all, bound to red blood corpuscles . Plasma half life and the apparent volume of distribution of chloramphenicol in horses were determined as 0.98 hours and 0.92 L/kg, respectively . At 5-10 mu g/ml concentrations in equine plasma approximately 30 percent of the chloramphenicol is bound to plasma proteins . From these studies it is concluded that the biological half life of chloramphenicol may be too short for therapeutic application against systemic infections in horses.

J Am Geriatr Soc, 1975 Apr, 23(4), 161 - 4
Pulmonary infections in elderly patients: treatment with cefazolin; Katz D et al.; The effects of cefazolin were studied in 15 hospital patients (average age, 67) with respiratory-tract infections . The infections were chiefly bronchopneumonia caused by organisms such as D . pneumoniae, Staph . aureus, or E . coli . In 13 of the 15 patients the results were excellent to good (eradication of the primary pathogen and clinical improvement); in the other 2 patients the response was fair . Intramuscular injection was well tolerated and only one patient complained of pain at the site of injection; no other adverse clinical effects were observed . In the laboratory determinations, including liver and kidney function tests, the only abnormalities were 2 cases in which the Coombs' test gave positive results without hemolysis . Cefazolin seems to be a safe and effective antibiotic for the treatment of respiratory-tract infections caused by cefazolin-susceptible organisms.

J Reprod Med, 1975 Apr, 14(4), 167 - 70
Male sterilization in El Salvador: A preliminary report; Madrigal V et al.; The expectation that male sterilization would not be an acceptable method of fertility control to the Latin American male has not been upheld in the initial phases of male sterilization programs in Colombia, Costa Rica, Guatemala, and El Salvador . On the contrary, in all of these programs and also at the Asociacion Demografica Salvadorena, a free-standing, non-profit family planning clinic in San Salvador, the initial success has been impressive, with 180 men accepting sterilization during the first two years (February, 1972 to February, 1974) . All sterilizations were performed by excising a 10-15 mm segment of each vas and ligating each vas end . Procedures were performed on an outpatient basis using a local anesthetic . Follow-up examinations were conducted at one week and three months after the procedure . Although complications were reported by 24.0% of the subjects at the one-week follow-up, the complications were minor: most were scrotal infections not requiring antibiotic therapy . Rates of complications were low for subjects returning for a three-month examination and semen test . Only one subject had a positive semen test.

Br J Surg, 1975 Apr, 62(4), 275 - 9
A controlled trial of parenteral prophylactic gentamicin therapy in biliary surgery; Keighley MR et al.; This trial has investigated the value of gentamicin therapy in patients requiring biliary surgery . One hundred consecutive patients were randomly allocated to receive either gentamicin or no antibiotic . Post-operative infection was assessed by an independent observer . Cultures and gentamicin assays were performed on bile and blood sampled during and after operation . The minimum inhibitory concentrations of gentamicin were measured with isolated bacterial . In 80 per cent of patients biliary organisms were inhibited by 2 mug/ml of gentamicin . Twice this concentration was found in the serum at operation in 88 per cent, but in the bile in only 18 per cent . Nevertheless, gentamicin lowered the incidence of bacteria in the bile from 42 to 25 per cent . There was a reduction in wound sepsis from 21 to 6 per cent (P less than 0-05) . Bacteriaemia was demonstrated in only 1 patient receiving gentamicin compared with 5 controls and 1 death occurred from endotoxaemia in the control group . These data suggest that gentamicin will reduce the morbidity of biliary surgery, particularly in patients in whom the bile is infected at operation.

Immun Infekt, 1975 Apr, 3(2), 65 - 71
{Virus infections of the respiratory tract in childhood (author's transl)}; Mietens C; Comprehensive epidemiological studies revealed that every individual is suffering from a respiratory tract infection in the average 6 times a year . 97% of these are caused by viruses . Identical clinical symptoms may be produced by many different agents, thus the etiology of an illness can only be identified by virus isolation and serological tests . The frequency of isolations is varying in adults and in children as well as in ambulatory and in hospitalized patients . The persistently observed susceptibility for new infections is caused by the great variety of possible etiologic agents especially in upper respiratory infections and the peculiarities of local immunity in the respiratory tract . An influence of chilling could not be demonstrated scientifically in spite of controverse clinical observations . It was proved however that allergic individuals succumb more frequently to viral infections . Overweight in infancy increases susceptibility for bronchitis and bronchiolitis . Superinfections by bacteriae are not rarely complications of viral diseases and antibiotic therapy may become necessary eventually . Leucocytosis and an elevated erythrocyte sedimentation rate are only criteria of limited value to distinguish viral and bacterial infections . Specific virostatic therapy is not possible so far for respiratory tract illnesses, but for prophylaxis of infections with influenza A2 amantadine-HCl may be used . Gammaglobulin has a prophylactic effect as well for certain virus infections but is of little use for antiviral therapy.

Arch Neurol, 1975 Apr, 32(4), 235 - 8
Mechanism of colistin-induced neuromuscular depression; McQuillen MP et al.; The effect of a high concentration of the antibiotic colistin sulfate on neuromuscular transmission was examined by recording intracellularly from rat diaphragm blocked with tubocurarine chloride . The presynaptic effect of colistin was different from that of neomycin sulfate, which reduces the probability of acetylcholine release: Colistin reduced that the quantum content of the initial and the last 20 end-plate potentials of a train of 40 stimuli without altering the probability of acetylcholine release . The quantum size was reduced, while the frequency of miniature end-plate potentials was unchanged.

J Biochem (Tokyo), 1975 Apr, 77(4), 745 - 52
Effects of reducing and oxidizing agents on the action of bleomycin; Onishi T et al.; The effects of reducing agents, such as 2-mercaptoethanol, dithiothreitol, L-ascorbic acid, or sodium borohydride, and oxidizing agents, such as hydrogen peroxide or dehydroascorbic acid, on the in vitro action of bleomycin were investigated . After the incubation of DNA with a low concentration of bleomycin and a reducing or oxidizing agent, single strand breaks were mainly caused in the DNA molecules . The degradation of DNA was largely prevented by the removal of oxygen, or by the addition of divalent cations or of S-(2-aminoethyl)isothiuronium bromide hydrobromide, a radical scavenger, to the incubation mixture . Preincubation of bleomycin with these reducing or oxidizing agents reduced the DNA-degrading activity of the antibiotic . However, this reduction in activity was observed even in the absence of oxygen, or in preincubation mixture supplemented with radical scavenger.

Gann, 1975 Apr, 66(2), 141 - 7
Optimum fractionation regimen for bleomycin treatment; Fukuda N et al.; A theoretical analysis was made on the optimum Bleomycin treatment regimen on the basis of the "binding-saturation model" which was proposed for the Bleomycin dose-cell survival relation . The surviving fraction of tumor cells decreased as a function of the number of fractionated treatments up to the optimum fractionation number if the tumor was treated with the same total dose . The effect of cellular sensitivity to the antibiotic, tumor doubling time, treatment interval, and total doses on the optimum regimen was analyzed . The importance of treatment interval and tumor doubling time was emphasized and the short treatment interval was recommended for the clinical use of this antibiotic . The optimum number of fractions increased linearly with the increase of the total dose while the optimum single dose was independent of the total dose . A concept of the tumor control probability of tumors treated with the optimum fractionation regimen was introduced and implications of these analyses in the clinical cancer chemotherapy were discussed.

Biochemistry, 1975 Mar 25, 14(6), 1230 - 5
Binding of manganese(II) to DNA and the competitive effects of metal ions and organic cations . An electron paramagnetic resonance study; Reuben J et al.; The binding of manganese(II) to DNA was studied by monitoring the concentration of free Mn2+ by electron paramagnetic resonance (EPR) . It was found that the association constnat of the Mn-DNA complex depends upon the degree of saturation . The competitive effects of magnesium, calcium, sodium, and a number of organic cations including the antibiotic drug daunomycin were analyzed and the parameters describing the cation-DNA interaction were evaluated . It was found that the association constant as well as the parameter describing its dependence upon the degree of saturation decrease along the series Mn, Mg, Ca, Na . Differences in the extent of interaction with the base nitrogens (N-7) are suggested as the possible mechanisms leading to these observations . The EPR spectrum of the manganese-DNA complex was found to be similar to that of manganese-nucleotide complexes suggesting a similar mode of coordination . A comparison of the results of competitive and direct binding studies reveals some salient features of the small molecule-DNA interaction and leads to the conclusion that manganese binds at the major groove of the DNA helix.

Biochim Biophys Acta, 1975 Mar 21, 383(3), 266 - 73
Steffimycin B, a DNA binding agent; Reusser F; The antibiotic steffimycin B binds to double-stranded DNA as evidenced by difference spectroscopy and an increase of the thermal stability of DNA in the presence of the antibiotic . Salmon sperm DNA-steffimycin B complexes show a drastic decrease in template activity for Escherichia coli DNA polymerase I but not for DNA-idrected RNA polymerase . The differences in template properties of poly{d(A-T)} and poly (dG) - poly(dC)-antibiotic complexes,respectively, for DNA polymerase I and RNA polymerase suggest that the antibiotic interacts primarily with adenine or thymine bases or both in double-stranded DNA.

Biochim Biophys Acta, 1975 Mar 20, 376(3), 533 - 48
Antimycin-insensitive mutants of Candida utilis II . The effects of antimycin on Cytochrome b; Grimmelikhuijzen CJ et al.; 1 . Cytochrome b-562 is more reduced in submitochondrial particles of mutant 28 during the aerobic steady-state respiration with succinate than in particles of the wild type . When anaerobiosis is reached, the reduction of cytochrome b is preceded by a rapid reoxidation in the mutnat . A similar reoxidation is observed in the wild type in the present of low concentrations of antimycin . 2 . In contrast to the wild type, inhibition of electron transport in the mutant has a much higher antimycin titre than effects on cytochromes b (viz., aerobic steady-state reduction; reduction in the presence of substrate, cyanide and oxygen; the 'red shift' and lowering of E'-o of cytochrome b-562) . Moreover, the titration curve of electron transport is hyperbolic whereas the curves for the reduction are sigmoidal . The conclusion is, that in both mutant and wild type, the actions of antimycin on electron transport and cytochromes b are separable . 3 . The red shift in the mutant is more extensive than in the wild type . 4 . Cytochrome b-558 and cytochrome b-566 (that absorbs in mutant and wild type at 564.5 nm) do not respond simultaneously to addition of antimycin, indicating that they are two separate cytochromes . 5 . The difference between the effect of antimycin on electron transport and cytochromes b reduction is also found in intact cells of the mutant . 6 . A model is suggested for the wild-type respiratory chain in which (i) the cytochromes b lie, in an uncoupled system, out of the main electron-transfer chain, (ii) antimycin induces a conformation change in QH-2-cytochrome c reductase resulting in effects on cytochrome b and inhibition of electron transport, (iii) a second antimycin-binding site with low affinity to the antibiotic is present, capable of inhibiting electron transport.

Nippon Naibunpi Gakkai Zasshi, 1975 Mar 20, 51(3), 129 - 47
{Studies on the mechanism of the diabetogenic activity of streptozotocin and on the ability of compounds to block the diabetogenic activity of streptozotocin (author's transl)}; Doi K; The present study was undertaken to clarify the mechanism of the diabetogenic activity of streptozotocin . Experiments were conducted to determine the resistance of animals to the diabetogenic action of streptozotocin; to follow the time course of irreversible beta-cell damage, and to determine the influence on streptozotocin action of certain compounds . Streptozotocin, a broad spectrum antibiotic, with antitumoral properties, was shown to be diabetogenic in rats and mice, but not in cats, rabbits, or guinea pigs . Intravenous or intraperitoneal administration of 65 mg/kg body weight of streptozotocin to male Wistar rats evoked a tri-phasic blood sugar response . It induced an initial hyperglycemic peak with no apparent change in plasma insulin concentrations, followed by profound hypoglycemia caused by liberation of large amounts of insulin from the pancreas . Forty-eight hours after injection, the animals were completely diabetic . Light- and electron-microscopic exadminations during the first forty-eight hours after the injection of streptozotocin showed pyknosis, degranulation and marked degeneration of the beta-cells . 1egenerative and necrotic changes were also seen in a few alpha-cells . These streptozotocin-induced diabetic rats revealed polydipsia, polyuria, polyphagia and glucosuria, and decreased body weight . Blood sugar, plasma FFA and insulin concentrations were examined after oral administration of glucose (OGTT: 3g/kg) . Blood sugar and plasma FFA were significantly elevated but plasma insulin concentrations were markedly decreased, so insulin treatments were most effective in these animals . It has been reported that nicotinamide prevents the diabetogenic activity of streptozotocin and the deformity action of 6-aminonicotinamide and 3-acetylpridine . Pre-treatment with picolinamide, methyl-nicotinamide, and nicotinohydroxamic acid also blocked its diabetogenic action, but nicotinic acid, mannoheptulose and glucose were ineffective . N-nitrosodimethylamin and ethyl-N-nitrosomethylcarbamate were devoid of diabetogenicity . It seems that streptozotocin interfers with NAD formation in the beta-cell . Functioning pancreatic islets cell tumors were observed on the rats both at 407 days after streptozotocin administration and at 473 days after streptozotocin administration with nicotinamide (500 mg/kg, i.p.).

Biochim Biophys Acta, 1975 Feb 24, 383(1), 9 - 15
Replication of mitochondrial DNA . Selective inhibition of the H-strand synthesis in isolated mitochondria by sibiromycin; Gause GG Jr et al.; Sibiromycin, an antitumour antibiotic forming a stable complex with the double-stranded DNA selectively inhibits the incorporation of {3H}thymidine into the H-strand of mtDNA during the incubation of isolated rat liver mitochondria in vitro . A model accounting for this result is presented . It is concluded that the H-strand is a leading strand throughout mtDNA replication adn consequently the replication of rat liver monomer mtDNA is unidirectional.

Antibiotiki, 1975 Mar, 20(3), 235 - 9
{Results of the long laboratory storage of Streptoverticillium hachijoense (Jamaguchi) Baldacci, the producer of trichomycin}; Konev IuE et al.; Viability, morphologo-cultural features and antibiotic properties of Sv . hachijoense, strain LIA-0052 stored for 10 years in a dry state and in the state of a resting culture were studied . Spores and mycelium of 2-week strains most stable to some chemical and physical factors were used for drying . It was found that viability of strain LIA-0052 was maintained for a longer period of time after lyophilization, in garden soil and agar culture under a layer of mineral oil . By the end of the observation period the viability of the soil culture decreased and the morphologo-cultural properties were stabilized . When the strain was cultivated on media with sucrose, the level of its antibiotic activity increased.

Antibiotiki, 1975 Mar, 20(3), 209 - 12
{Effect of the aeration conditions on the biosynthesis of oxytetracycline and the formation of organic acids by a culture of Actinomyces rimosus}; Oblozhko LS et al.; The effect of the aeration conditions on oxytetracycline biosynthesis and production of organic acids by Act . rimosus was studied . Intensive biosynthesis of oxytetracycline in shaken flasks with concentrated complex media was observed at the rate of oxygen dissolution in the liquid ranging from 14 to 25 mg/1/min . Lower rates of the oxygen dissolution up to 7 mg/1/min resulted in decreased rates of the culture growth and the medium component consumption, decreased antibiotic levels, production of significant amounts of pyruvic and acetic acids.

Am J Dig Dis, 1975 Mar, 20(3), 214 - 22
Clindamycin-associated colitis; Unger JL et al.; Four cases of clindamycin-associated colitis have recently been observed at Kansas University Medical Center . There have been a few reports in the literature of colitis associated with this antibiotic, and our 4 cases are similar to those noted previously . All had the onset of diarrhea 7-14 days following the initiation of clindamycin therapy; the diarrhea persisted for weeks after the drug was discontinued . Mucosal changes ranged from focal ulceration to pseudomembrane formation . Diarrhea in a patient on clindamycin should alert the physician to the possibility of antibiotic induced colitis, a condition with significant morbidity and occasional mortality.

Schweiz Med Wochenschr, 1975 Mar 1, 105(9), 257 - 63
{Antiinfectious chemotherapy in pregnancy}; Mosimann W; Antibiotic therapy during pregnancy is generally given to treat infectious diseases of the mother rather than of the fetus . Despite her altered physiology the pregnant woman poses few specific pharmacokinetic problems . The main concern is possible damage to the fetus, depending on its developmental stage at the time of administering the drug . Largely on an empirical basis, antibiotics which can be administered without hazard throughout pregnancy are distinguished from those which should be completely avoided during pregnancy and from others which must be omitted during certain phases of pregnancy . Similar considerations apply in the case of drugs used for the treatment of tuberculosis and mycoses.

Am J Physiol, 1975 Mar, 228(3), 693 - 8
Renal glutaminase adaptation and ammonia excretion in infant rats; Benyajati S et al.; The purpose of this investigation was to determine the role of enzyme adaptation in the response of ammonia excretion to acidosis in developing rats . The response of renal ammonia excretion was low in infant rats (7-12 days old) following administration of a single dose of acidifying salt (5 mmol NH4CL/kg) . However, repeated administration (2 times daily) of the salt increased ammonia excretion two- to threefold within 2 days . This adaptive response was associated with a concomitant rise in renal phosphate-dependent glutaminase (PDG) activity; PDG activity increased from approximately 36% adult level in untreated infants to 79% adult level in infants given NH4Cl for 2 days . Ammonia excretion and PDG activity decreased in parallel following cessation of NH4Cl treatment . Administration of the antibiotic, actinomycin D (100 mug/kg, ip, 2 times daily for 2 days) completely inhibited the response of PDG to repeated NH4Cl administration . In contrast to the situation previously observed in adult rats, actinomycin D treatment prevented the acid-induced rise in renal ammonia excretion . These results suggest that the level of renal PDG plays a more direct role in the adaptation of ammonia excretion to acidosis in infant rats than in adults.

Biokhimiia, 1975 Mar-Apr, 40(2), 263 - 6
{Stimulation of rna synthesis by chloramphenicol}; Shchakupov RC et al.; The influence of different concentrations of chloramphenicol on the RNA synthesis was studied in E . coli strains CP 78 (rel+) and CP 79 (rel-) . In cells growing in the medium with succinate as a carbon source the maximal stimulation of RNA synthesis was obtained in the presence of 5-10 mug/ml of chloramphenicol-that is when the protein synthesis in the cells is decreased to 50-30% . Concentrations of antibiotic 50-100 mug/ml only slightly stimulate the incorporation of 14C-uracil in TCA-insoluble fraction . The high level of RNA synthesis once achieved in the presence of small doses of chloramphenicol was not affected by higher concentrations of antibiotic up to 105 mug/ml . It is suggested that at low doses of chloramphenicol some proteins of positive control of RNA synthesis are synthesized . Under amino acids starvation in the presence of succinate only rel+ cells stopped RNA synthesis . The phenotypic suppression of RNA synthesis with chloramphenicol in these cells is achieved only by high concentrations of antibiotic (50-100 mug/ml) . It is proposed that under amino acid starvation RNA synthesis is independent on the protein formation and is determined by relative contents of programmed ribosomes in cells.

Antibiotiki, 1975 Mar, 20(3), 266 - 71
{Intrauterine sensitization to benzylpenicillin in an experiment on rabbits}; Kovalenko LP et al.; Antibodies of benzylpenicillin in the posterity of various ages of female rabbits were found with reaction of passive hemagglutination (RPHA) and degranulation of the basophiles after their immunization with the antibiotic . This provided an assumption of intrauterine sensitization . Treatment of the sera of the sensitized animals with 2-mercaptoethanol partially decreased their activity in the RPHA which indicated to the presence of the antibodies of classes IgG and IgM.

Nucleic Acids Res, 1975 Mar, 02(3), 391 - 404
(dA-dT) dependent inactivation of the DNA template properties by interaction with netropsin and distamycin A; Wahnert U et al.; The inhibitory effect of the polypeptide antibiotics netropsin and distamycin A on DNA dependent nucleic acid synthesis has been shown to be related to the base composition of the template DNA . A number of natural DNA's of quite different dA-dT content as well as poly (dI-dC)-poly (dI-dC), poly (dA-dT)-poly (dA-dT), poly (dA) - poly (dT) and poly (dG) - poly (dC) has been studied as templates in DNA and in part in RNA polymerase reaction . The highest binding efficiency of netropsin existing for (dA-dT) - containing DNA polymers and the less pronounced interaction with the (dI-dC)-containing polymer shown by the melting and CD spectrral behaviour of the complexes are entirely reflected in the template inactivation . The same is evident for distamycin A . However, in contrast to netropsin the antibiotic distamycin A exhibits some binding tendency to poly (dG) - poly (dC) . Binding effects of a netropsin derivative to DNA and (dA-dT) -containing polymers suggest the importance of hydrogen bonds of the peptide groups in the complex formation.

Am J Ophthalmol, 1975 Mar, 79(3), 502 - 9
Endogenous Aspergillus endophthalmitis occurring after kidney transplant; Naidoff MA et al.; Two months after renal transplantation, a 26-year-old man developed pneumonia that was recalcitrant to antibiotic therapy and proved by biopsy to be due to cytomegalovirus and Aspergillus fumigatus . Ten days later while on amphotericin B therapy, he developed an endophthalmitis proved by smear and culture of a vitreous aspiration to be caused by A . fumigatus . Despite intravitreous and systemic amphotericin B the vision deteriorated and the eye was enucleated . Microscopic examination disclosed an intense endophthalmitis with vitreous and retinal abscesses . The second patient was a 29-year-old woman who developed severe hypertension and graft rejection one month after renal transplant, despite massive immunosuppressive therapy with prednisone, azathioprine, and cobalt 60 irradiation . She developed pneumonia, meningitis, and died . A postmortem examination revealed disseminated aspergillosis . A single choroidal abscess due to Aspergillus with an associated retinal hemorrhage was observed in the left eye.

J Bacteriol, 1975 Mar, 121(3), 1000 - 6
F deoxyribonucleic acid transferred to recipient cells in the presence of rifampin; Hiraga S et al.; When Escherichia coli F+ cells resistant to rifampin and streptomycin are mated with F- cells sensitive to the antibiotics, a large fraction of F factor deoxyribonucleic acid (DNA), which is transferred to the recipient cells in the presence of either of the antibiotics, can be recovered as covalently closed, circular double-stranded DNA, as in the control mating in the absence of antibiotic . Similar results were obtained in the presence of chloramphenicol or chloramphenicol plus rifampin . It is suggested that the transferred single-stranded F DNA can be converted to the covalently closed, circular double-stranded form in the absence of protein synthesis, and that rifampin-sensitive transcription is not required for the conversion.

Rev Rhum Mal Osteoartic, 1975 Mar, 42(3), 153 - 9
{Etiological diagnosis of spondylitis . II . Vertebral puncture biopsy and surgical approach}; Caroit M et al.; The authors tried to determine the ways in which vertebral puncture biopsy and the direct surgical approach can helpin the etiological diagnosis of spondylodiscitis, when the clinical radiological, and laboratory examination leave the clinician in doubt . Out of 28 vertebral puncture biopsies, proof of tuberculosis was obtained in 4 cases, and proof of a non-tuberculous cause was obtained in 1 case as a result of isolating the responsible organism . Thirty-eight cases were submitted to the direct surgical approach . When the indication for surgery was solely in order to investigate the etiology, proof of tuberculosis was obtained in half of the cases, and only exceptionally was a non-tuberculous organism discovered . In almost half the cases, the histological characteristics were non-specific and no organisms were detected . Most of these latter cases were, in fact, non-tuberculous spondylodiscitis, although subsequently some of them exhibited evidence of a tuberculous character . In the present state of knowledge, it seems that, in cases of clearly non-tuberculous spondylodiscitis, the direct surgical approach is not justified if the objective is solely to isolate the organism, so that its sensitivity to antibiotics can be tested . The following reasons are given for this conclusion : the direct surgical approach only rarely leads to isolation of the causal organism; although treatment based on knowledge of antibiotic sensitivity may help to restrict evolution of the disease, it does not reduce significantly, or only rarely, the permanent partial incapacity . If the results published by Seignon and Gougeon are confirmed, early needle puncture of the diskovertebral centre of the disease should be practised more widely.

J Pharm Sci, 1975 Mar, 64(3), 516 - 9
Drug-biomolecule interactions: interaction of gentamicin with lipid monomolecular films; Auslander DE et al.; The interaction of gentamicin with monomolecular films of a series of biologically important lipids spread on an aqueous buffered subphase was studied . The surface pressure, pi, of these films was determined by the Wilhelmy plate method as a function of surface area, A, and pi-A curves were constructed . Changes in the pi-A characteristics in the presence of gentamicin were used as a measure of antibiotic-film interaction . No interaction was observed between gentamicin and films of cholesterol, egg lecithin, dipalmitoyl lecithin, phosphatidyl ethanolamine, stearyl alcohol, and bovine ceramides at all pH values studied . Stearic acid films showed no interaction with gentamicin at pH 5 . At pH 7 and 8, a small increase in pressure (approximately 3 dynes/cm) was noted . A dramatic increase in surface pressure was observed in the presence of stearyl aldehyde films ranging from approximately 9 dynes/cm at pH 7,2 to 23 dynes/cm at pH 8.4 . This effect was attributed to a Schiff-base reaction between the nonprotonated primary amino groups on the gentamicin molecule and the stearyl aldehyde . Further evidence was reported by the fact that the addition of glucose (which has been reported to participate in Schiff-base formation with amines) to the subphase inhibited the stearyl aldehyde-gentamicin interaction . Sucrose did not show a corresponding effect . The addition of sodium bisulfite, which reacts with aldehydes to form alpha-hydroxysulfonic acid, also inhibited the gentamicin-stearyl aldehyde interaction . It is postulated that Schiff-base formation is a step in the in vivo transport of gentamicin across the membrane of sensitive organisms.

Antibiotiki, 1975 Mar, 20(3), 232 - 5
{Action of migillin on its own producer, Asp . fumigatus}; Tu Minh Kuong et al.; Addition of migillin to the nutrient medium at early stages of the fungus development induced at one hand inhibition of the fungus growth during the first 24-48 hours and stimulation of the biomass accumulation during the following hours of the development and on the other hand it induced inactivation of migillin added and inhibition of production of the "own" antibiotic . The migillin effect was accompanied by a delay in liberation of the substance with adsorption at 260nm from the mycelium.

Mycopathologia, 1975 Feb 28, 55(1), 5 - 8
{Antibiosis shown by a strain of Byssochlamys nivea Westling, 1909 . III . Chromatographic characteristics and isolation of the active fraction}; Colin AM et al.; Early papers revealed that culture filtrate of Byssochlamys nivea has antibiotic properties . Active filtrate of B . nivea is extracted with ethyl acetate . Paper chromatography is carried out on Whatman no . 1; thin-layer chromatography is carried out on Kieselgel; visualization with bioautographic technique reveals a single spot . Ethyl acetate extract is passed through silicic acid-celite column . Each isolated fraction is tested for antibiotic activity . Only one supports this activity; a crystallized matter, melting point 109-110 degrees C, thermostable, is obtained.

Eur J Biochem, 1975 Feb 21, 51(2), 579 - 85
Chlorothricin, and inhibitor of porcine-heart malate dehydrogenases, discriminating between the mitochondrial and cytoplasmic isoenzyme; Schindler PW; The macrolide-type antibiotic chlorothricin was found to inhibit both the mitochondrial and the cytoplasmic form of pig heart malate dehydrogenase . Steady-state kinetic measurements revealed that in the direction of oxalacetate reduction chlorothricin is competitive with respect to NADH and non-competitive with respect to oxalacetate . Both the variation of initial velocity with NADH concentration in the presence of antibiotic, and, at several fixed levels of NADH, the variation of initial velocity with chlorothricin concentration deviates from the classical Michaelis-Menten relationship for the two isoenzymes . Since, despite the very similar kinetic behaviour of the mitochondrial and cytoplasmic species of malate dehydrogenase, the concentration of chlorothricin required for half-maximal inhibition of the two enzymes differs by more than a factor of 10 (the mitochondrial isoenzyme being more susceptible to inhibition), it is concluded that the NADH binding sites of the mitochondrial and cytoplasmic form of malate dehydrogenase from pig heart are different.

Biochim Biophys Acta, 1975 Feb 17, 376(2), 249 - 58
Control of proton translocation induced by ATPase activity in chloroplasts; Carmeli C et al.; 1 . Proton uptake was induced by ATP in the dark following light triggering of ATPase activity in chloroplasts . The accumulated protons were released when ATPase activity was inhibited by the energy transfer inhibitor DIO-9 . 2 . Approximately two protons were taken up for each ATP hydrolyzed at pH 8 . A drop in H+/ATP ratio was caused by uncouplers such as NH4Cl and carbonyl cyanide p-trifluoromethoxyphenylhydrazone . These uncouplers caused an increase in the rate of ATP hydrolysis without a corresponding increase in proton uptake . 3 . The energy transfer inhibitor dicyclocarbodiimide inhibited both ATPase activity and the rate of proton uptake without changing the H+/ATP ratio . 4 . The antibiotic valinomycin caused an increase in the rate of both proton uptake and ATP hydrolysis without altering the ratio of H+/ATP . The H+/ATP ratio varied with changes in the external pH . The results were discussed in view of the chemiosmotic theory of oxidative and photosynthetic phosphorylation.

Biochim Biophys Acta, 1975 Feb 10, 378(3), 439 - 49
Effects of extracts of rat tissues on the action of bleomycin; Onishi T et al.; The cell sap (105 000 times g supernatant) of various tissues of rats caused DNA degradation in the presence of bleomycin . The activity was fractionated into two peaks by column chromatography on Sephadex G-25 . The activity in Peak A (excluded fraction) appeared to be due to some proteinaceous entity, while that recovered in Peak B (retarded fraction), constituting about 90% of the total activity, seemed to be due to ascorbic acid, judging by results of further gel filtration and the effect of treatment with ascorbate oxidase . Incubation of bleomycin with Peak A or B caused loss of the ability of the antibiotic to degrade DNA . It is proposed that the action of bleomycin on DNA, and its inactivation by tissue extracts, depend, at least in part, on the presence of ascorbic acid.

J Biol Chem, 1975 Feb 10, 250(3), 939 - 45
Energy coupling in the uptake of hexose phosphates by Escherichia coli; Essenberg RC et al.; Several methods were used to study the source of energy in the uptake of hexose phosphates by Escherichia coli K12 . The uptake was sensitive to inhibition by agents that affect electron transport, such as lack of oxygen, cyanide, and heptylhydroxyquinoline-N-oxide, and by agents that affect ATP utilization, such as dicyclohexylcarbodiimide and arsenate . It was also sensitive to uncouplers in the presence of absence of oxygen . The strain of E . coli used extruded protons during respiration . Uncer anaerobic conditions, the uptake of approximately 1 eg to H+ per glucose 6-phosphate . These observations are consistent with a chemiosmotic mechanism of genergized glucose 6-phosphate uptake . The rate of glucose 6-phosphate uptake was maximal in KC1, but was also stimulated by MgC12 or CaC12 . Inhibition by A217, a nigericin-like antibiotic, was prevented by K+ whereas valinomycin and gramicidin inhibited in the presence or absence of K+.

No Shinkei Geka, 1975 Feb, 3(2), 163 - 9
{Abscess of the brain (2nd report)--special reference to surgical indication of extracapsular excision of brain abscess (author's transl)}; Shinoara T et al.; Brain abscess persists as a serious diagnostic problem and critical therapeutic challenge since pre-antibiotic era . After antibiotic agents has been introduced, abscess of the brain seems to be a surgical curable intracranial suppurative disease, although surgical mortality and morbidity due to brain abscess are still distressingly high . Recently, the incidence of brain abscess are gradually increasing . In this present situation, it is necessary to reevaluate the previous method and surgical results of brain abscess . Even with new surgical techniques and antibiotics, the mortality rate and number of neurological deficits remain high, as previously methods, it is most important how to eliminate these problems . It was undertaken to determine the significant factors affecting the clinical management of patients with this serious problem . The general outlines of our neurosurgical treatment are given, with emphasis on our surgical schedule of brain abscess, especially brain abscess in congenital heart disease . In this paper, a review of the current status of the surgical methods, operative mortality and morbidity, diagnostic methods and the therapy of brain abscess has been discussed.

J Assoc Physicians India, 1975 Feb, 23(2), 161 - 4
Hyperlipidaemia and pancreatitis associated with oral contraceptive therapy; Mehrotra TN et al.; PIP: Case reports of 2 patients who developed pancreatitis and hyperlipidemia while using oral contraceptives are presented . The 1st patient had been taking Ovulen for 2 years when severe abdominal pain suddenly developed . Initially cholecystitis was diagnosed . Symptoms subsided within 1 week but recurred 2 months later, when the white blood count was increased to 16,400/cubic mm . Serum was grossly lipemic with a triglyceride level of 3500 mg% and serum cholesterol 560 mg% . 3 days later triglycerides had fallen to 400 mg% and cholesterol to 270 mg% . Cholecystography was normal . The pain had subsided . Symptoms have not recurred since stopping use of Ovulen . The 2nd patient was admitted with severe abdominal pain of 48 hours duration . Similar attacks of pain had occurred previously but had been of short duration . She had been taking Ovulen for 3 years . White blood count was increased to 18,000 . Serum was grossly lipemic . Serum glyceride concentration was 7000 mg% and cholesterol 1200 mg% . Afer 3 days triglycerides were 500 mg% and cholesterol 475 mg% . Pancreatitis was diagnosed . Therapy was Ryles tube suction, atropine, intravenous saline, and a broad spectrum antibiotic . Symptoms subsided in 10 days . The hyperlipidemia is thought to have been a primary condition causing the pancreatitis . {Patients known to have such a condition should avoid use of oral contraceptives .

Arch Intern Med, 1975 Feb, 135(2), 240 - 3
Brucellosis outbreak attributed to ingestion of umpasteurized goat cheese; Young EJ et al.; In six cases of Brucella melitensis infections the common etiologic factor was the ingestion of raw goat cheese . Presenting complaints were variable, but a constant feature was persistent fevers that frequently were present for months . Evidence of liver cell dysfunction was present in each case, and in two, biopsy disclosed diffuse hepatitis with focal necrosis . The diagnoses were initially based on high titers of Brucella agglutinins and later confirmed by positive blood cultures . A good clinical response was induced by antibiotic therapy ( tetracycline plus streptomycin sulfate), but in two cases a Jarish-Herxheimer reaction occurred during the first 24 hours of treatment.

Eur J Pharmacol, 1975 Feb, 30(2), 272 - 9
Direct myocardial depressant effects of gentamicin; Adams HR; Effects of gentamicin on myocardial contractile performance were examined in isolated, electrically driven, rat left atria . This aminoglycoside antibiotic produced a maintained and concentration-dependent (0.0156-0.25 mM) depression of myocardial contractile tension that was reversible by replacing the incubation media with gentamicin-free solution . Time to peak tension and total contraction time were not discernibly altered by gentamicin . The negative inotropic response elicited by gentamicin was antagonized in a competivitive-like manner by increasing the calcium ion (Ca2+) concentration of the bathing solution, whereas, the depressant effects of gentamicin were antagonized by norepinephrine in a non-competitive-like manner . Present findings demonstrate a direct negative inotropic effect of gentamicin and suggest that this antibiotic interferes with the participation of Ca2+ in the events leading to mecahnical activity of atrial myocardium.

Antibiotiki, 1975 Feb, 20(2), 158 - 61
{Toxic action of morphocycline on pregnant rats}; Slonitskaia NN et al.; Morphocycline was administered intravenously to rats of Wistar line in doses of 100, 50 and 20 mg/kg at various periods of pregnancy . It was found that a single administration of morphocycline in the above doses to the rats on the 9th day of their pregnancy resulted in abortus in some female rats . Death and resorption of the fetus were more frequent after the antibiotic use in doses of 20 and 50 mg/kg . Repeated administrations of morphocycline in doses of 20 mg/kg resulted in abortus and postimplantation death of the fetus most pronounced in the animal groups treated with the antibiotic during the periods of the 7th to the 10th and from the 11th to the 14th days of pregnancy . The teratogenic activity of morphocycline was slightly pronounced . It was observed in some fetus after both single and repeated administrations of the antibiotic.

J Antibiot (Tokyo), 1975 Feb, 28(2), 143 - 8
Neocarzinostatin-induced breakdown of deoxyribonucleic acid in HeLa-S3 cells; Ohtsuki K et al.; Degradation of DNA in HeLa-S3 cells mediated by an acidic antitumor protein, neocarzinostatin (NCS), was examined . The concentration of NCS required for induction of DNA degradation was considerably higher than that which caused inhibition of DNA synthesis . Sedimentation analysis of DNA revealed that HeLa-S3 cell DNA first received single-strand nicks within 60 minutes after exposure to the antibiotic, whereas detectable double-strand scissions eventually gave rise to the accumulation of double-stranded DNA fragments of heterogeneous size . When the cells exposed to NCS were transferred to NCS-free medium at early stages of the degradation, the single-strand nicks caused in DNA were repaired by a process which was sensititive to puromycin.

Genetics, 1975 Feb, 79(2), 175 - 86
A new method for mutant selection in Saccharomyces cerevisiae; Henry SA et al.; A new method for the selection of auxotrophic, antibiotic- and temperature=sensitivemutants in Saccharomyces cerevisiae is reported . The technique is based upon the observation that certain fatty acid auxotrophs of yeast die when deprived of fatty acid only under conditions supporting growth . When macromolecular synthesis is blocked, the fattyacid-starved cells survive . By appropriate manipulation of a fatty acid-requiring strain enrichment as great as 75-fold was achieved for certain classes of auxotrophic mutants . An enrichment of approximately 100-fold is possible for some antibiotic-sensitive mutants . Selection for temperature-sensitive mutants, however, resulted in less than a 2-fold increase in the frequency of such mutants, probably because of the heterogeneity ofthis mutant category . It is likely that only that fraction of temperature-sensitivemutations which rapidly and reversibly blocks macromolecular synthesis is selected by this technique.

Ann Surg, 1975 Feb, 181(2), 213 - 9
Roux-en-Y hepaticojejunostomy: a reappraisal of its indications and results; Stefanini P et al.; A critical evaluation is made of 131 patients submitted to choledocho or hepaticojejunostomy . The main indications for hepaticojejunostomy were iatrogenic strictures of CBD (60 patients), and choledocholithiasis with markedly dilated duct (41 patients) . The overall mortality rate was 4% representing principally renal hepatic failure, bile peritonitis and bleeding . The complications following hepaticojejunostomy included only in one case biliary fistula which required reoperation . The long-term results of 80 patients available for a followup study were as follows: 63 patients (78.7%) were symptom-free at 2-13 years followup; 8 patients had brief episodes of cholangitis which responded to antibiotic and corticosteroid treatment; 9 patients required reoperation for stricture of anastomosis . These overall results are a strong argument for hepaticojejunostomy which, compared with choledochoduodenostomy, avoids the hazards of the so-called sump syndrome and of the reflux of enteric contents in the CBD . An increased incidence of peptic ulcer disease in the patients submitted to hepaticojejunostomy was not observed . In very high strictures and in reinterventions anastomosis between left hepatic duct and Roux-en-Y jejunal limb was carried out . The results achieved with this technique, which was performed in 26 patients, were about the same following hepaticojejunostomy.

J Virol, 1975 Feb, 15(2), 305 - 15
Vaccinia virus infection of HeLa cells . I . Synthesis of vaccinia DNA in host cell nuclei; LaColla P et al.; The replication of vaccinia virus is thought to take place exclusively in the cytoplasm of host cells . However, using DNA-DNA hybridization techniques, it can be shown that a significant fraction of the synthesis of vaccinia DNA takes place in the nucleus as well as the cytoplasm . The (3H) thymiding pulse-labeled vaccinia DNA synthesized in the nucleus reaches a maximum at about 3 h after infection, corresponding to the time of maximal DNA synthesis in infected cells . At this time host DNA synthesis drops to about 25% of the rate of the uninfected cells . Even with short labeling times (2 min) the nucleus is found to contain 60% of the incorporated (3H)thymidine, much of which is in vaccinia DNA . Prior inhibition of host nuclear DNA synthesis with mitomycin C, followed by removal of the antibiotic causes a subsequent inhibition of vaccinia DNA synthesis and complete suppression of mature virus . Purified nuclei, isolated from vaccinia-infected cells, also synthesize vaccinia DNA in vitro . Over 90% of the DNA synthesized in vitro by isolated nuclei contain vaccinia-specific sequences.

Biochim Biophys Acta, 1975 Jan 31, 376(1), 82 - 8
Energy transduction in photosynthetic bacteria . VIII . Activation of the energy-transducing ATPase by inorganic phosphate; Melandri AB et al.; ATPase activity and ATP-induced energization of photosynthetic membranes from Rhodopseudomonas capsulata are stimulated by phosphate; the maximum stimulatory effect occurs at a concentration between 1 and 2 mM . The sensitivity of the ATPase to oligomycin increases in the presence of phosphate since all the Pi-stimulated activity is inhibited by this antibiotic . Aurovertin, which has no effect on ATPase in the absence of phosphate, inhibits completely the activity elicited by this anion . The addition of Pi induces a substantial increase in the V of ATPase activity without changing the affinity of the enzyme for ATP or ADP . Arsenate, at the same concentrations, produces effects very similar to those of phosphate . The stimulation by arsenate of the transfer of energy from ATP to the membrane suggests a non-hydrolytic role of this anion as a modifier of the ATPase activity.

Biochemistry, 1975 Jan 28, 14(2), 420 - 9
Studies of individual amino acid residues of the decapeptide tyrocidine A by proton double-resonance difference spectroscopy in the correlation mode; Gibbons WA et al.; The cyclic decapeptide antibiotic tyrocidine A was studied by two relatively new methods, viz., correlation proton magnetic resonance (pmr) spectroscopy and double-resonance difference pmr spectroscopy . The correlation method of spectral accumulation provided pmr spectra of good resolution, and in addition the signal-to-noise ratio achieved per unit time of accumulation was much higher than that achieved by use of the conventional continuous wave (cw) method . Furthermore, when protonated solvents are used, the correlation mode of accumulation has a distinct advantage over pulse and fast Fourier transform (fft) methods currently in use . Double-resonance difference (drd) spectra of individual amino acid residues in tyrocidine A were obtained by the correlation method when the decoupling frequency was maintained at the center frequency of the appropriate C-alpha proton multiplet and at a level of power that totally decoupled vicinal C-alpha and C-beta protons; the resolution of these spectra was good, and the signal-to-noise ratio was high . The distinct patterns and spectral positions of the drd spectra were characteristic of the particular type of amino acid residue and, therefore, could be used as the basis for making assignments . Furthermore, the drd spectra revealed the spectral positions of individual C-alpha and C-beta proton transitions and therefore, upon spectral analysis, could provide the chemical shifts and coupling constants of these protons . Positions of transitions were revealed even though they were hidden by overlap in the corresponding conventional single- or double-resonance spectra.

Mol Gen Genet, 1975, 137(3), 269 - 76
Cytoplasmic and nuclear mutations to chloramphenicol resistance in Aspergillus nidulans; Gunatilleke IA et al.; Two chloramphenicol resistance mutations out of 123 tested in Aspergillus nidulans are inherited extranuclearly as judged by transmissibility in heterokaryons, lack of segregation at meiosis, and independent segregation from all of the eight nuclear linkage groups . They do not recombine with each other . However, experiments in collaboration with G . Turner and R.T . Rowlands show that they do recombine with cytoplasmic mutations to oligomycin resistance (Rowlands and Turner, 1973) and cold-sensitivity (Waldron and Roberts, 1973) . These cytoplasmic chloramphenicol resistance mutations are stable and do not affect growth or morphology on antibiotic-free media . Nuclear mutations to chloramphenicol resistance map at a minimum of three loci . At one of these loci, most, but not all, mutations lead pleiotropically to cycloheximide hypersensitivity, and most of these, but not all, also confer pleiotropic hypersensitivity to salicylhydroxamic acid.

Vet Rec, 1975 Jan 11, 96(2), 38 - 9
The induction, persistence and loss of framycetin sulphate resistance in enteric E coli of pigs; O'Brien JJ et al.; When framycetin sulphate was fed at prophylactic levels to pigs, resistance to this antibiotic was induced within days in the enteric E coli . The E coli of the gut did not become fully susceptible again until six to seven weeks after the anitbiotic was withdrawn from the diet.

Eur J Biochem, 1975 Jan 2, 50(2), 391 - 402
The binding of tritiated elongation factors 1 and 2 to ribosomes from Krebs II mouse ascites tumor cells; Nolan RD et al.; Tritiated elongation factors 1 and 2 (EF-1 and EF-2) were obtained from Krebs II ascites cells which had been grown in mice injected with radioactive amino acids . The highly purified factors were sufficiently radioactive to be used in a study of the interactions between ribosomes and elongation factors . The following results were obtained . 1 . EF-1 binding to ribosomes requires the presence of a polynucleotide, an aminoacyl-tRNA specified by the latter and a guanosine nucleotide carrying three phosphate groups . The hydrolysis of the GTP molecule involved in the binding reaction leads to the immediate release of EF-1 . If GTP is replaced by Guo-5'-P2-CH2-P the factor remains bound to the ribosome and can be detected by sucrose gradient centrifugation techniques . 2 . Likewise EF-2 binding to ribosomes can only be detected in the presence of GUO-5'-P2-CH2-P . 3 . The affinity of ribosomes for EF-2 appears to be higher than for EF-1: PREINCUBATION OF RIBOSOMES WITH EF-2 inhibits the subsequent attachment of EF-1 almost completely . EF-1 prebound to ribosomes in the presence of GUO-5'-P2-CH2-P, POLY(URIDYLIC ACID) AND Phe-tRNA-Phe is partially removed from the ribosomes together with Phe-tRNA during a second incubation with EF-2 . 4 . Although EF-2 binding to ribosomes precludes any stable association between ribosomes and EF-1 it does not prevent the insertion of aminoacyl-tRNA into the ribosomal A-site . The attachment of aminoacyl-tRNA under these conditions enhances the binding of EF-2 to the ribosome . 5 . The antibiotic showdomycin strongly inhibits the attachment of EF-1 to ribosomes and to a lesser degree impairs the binding of EF-2 . 6 . A-site ribosomes display a strong preference for the attachment of EF-2 and bind EF-1 only very poorly . The reverse is true for P-site ribosomes which are good substrates for the binding of EF-1 and bind EF-2 less efficiently than A-site ribosomes . These results and a number of additional findings made in this and in previous studies are discussed in the general context of the structure and function of mammalian elongation factors 1 and 2.

Eur J Biochem, 1975 Jan 2, 50(2), 317 - 23
The involvement of sulphydryl groups in the peptidyl transferase centre of eukaryotic ribosomes; Carrasco L et al.; Treatment of mammalian ribosomes with N-ethylmaleimide enhances up to 100% the ribosome efficiency in the "fragment reaction assay" for peptide bond formation by increasing the affinity of the substrate C-A-C-C-A-Leu-Ac for the donor site . This stimulation in peptidyl transferase activity was not observed when yeast ribosomes were treated in a similar manner . Stimulation of the peptidyl transferase activity of mammalian ribosomes was also observed by treatment with either p-chloromercuribenzoic acid or 5,5'-dithiobis-(2-nitrobenzoic acid) or 5,5'-dithiobis-(2-nitropyridine) or the maleimide-derived antibiotic showdomycin . N-Ethylmaleimide treatment also enhances C-A-C-C-A-Leu binding to the acceptor site of the peptidyl transferase centre . However, neither binding of N-Ac-Phe-tRNA in the presence of ethanol, nor binding of Phe-tRNA to the ribosomes is stimulated by N-ethylmaleimide . The antibiotic tenuazionic acid (a selective inhibitor of peptide bond formation by mammalian ribosomes) appears to require for its inhibitory effect the ribosome sulphydryl residues, since its inhibitory action on the fragment reaction is greatly decreased in ribosomes treated with N-ethylmaleimide.

Probl Khig, 1975, 1, 165 - 70
{Changes in the liver transport of bile pigments in certain forms of jaundice under the influence of novobiocin and luminal}; Goranov I et al.; The novobiocin and luminal test application increases the possibilities to differentiate premicrosome from postmicrosome jaundice and extends the knowledge on hyperbilirubinemia pathobiochemistry . Novobiocin (an antibiotic) inhibits the conjugation and glucuronidizing of bile pigments . Accordingly, the novobiocin test is strongly positive in any premicrosome jaundice form--Gilberts's disease, posthepatitis hyperbilirubinemia (PHHB) and hemolytic jaundice . It is negative in hepatocellular and hepatocanalicular jaundice, and in Dubin-Johnson's syndrome . In premicrosome jaundice with fluctuating bilirubinemia and normal bilirubin level at the time of examination, the novobiocin test may bring about manifestation of a latent or temporary compensated defect which proves to be most helpful in diagnosing . It is assumed that hemolytic jaundice is caused, apart from bile pigments hyperproduction, also by concomitant disorders in the intrahepatal transport of bile pigments . The latter hypothesis is corroborated by the data of the study . The luminal test is likewise markedly positive in premicrosome jaundice, and negative--in chronic hepatocellular and hepatocanalicular jaundice . In some instances with slight defect in the intrahepatal transport of pigments, the luminal test accounts for normalization of bilirubinemia and of the direct to total bilirubin ratio . The test is moderately positive in the syndrome of Dubin-Johnson . The latter fact supports the hypothesis that luminal, alongside the effect on transport mechanisms, exerts influence on bile pigments excretion also.

Eur Urol, 1975, 1(3), 157 - 8
Doxycycline levels in prostatic tissue and blood; Mathisen W et al.; Doxycycline was administered orally to 23 patients scheduled for prostatectomy or radical cystectomy . Blood and prostatic tissue samples were collected simultaneously during operation and subsequently assayed for doxycycline levels . The concentration of doxycycline in the prostatic tissue was on average 2.75 mug/g which is far above the therapeutic level . The lowest level recorded was 0.85 mug and the highest was 4.81 mug . The findings suggest a tendency for this antibiotic to accumulate in prostatic tissue . This is in agreement with the clinical observations of the good effect of doxycycline treatment in patients with chronic bacterial prostatitis.

Med Pediatr Oncol, 1975, 1(2), 175 - 81
Intravenous catheter infection study: a prospective trial in patients with neoplastic disease; Feld R et al.; This study was designed to determine the frequency and significance of infection at the site of indwelling intravenous catheters . Eligible patients were randomly assigned to have an intravenous infusion utilizing either a plastic cannula or or a short metal needle . Both of these groups were further randomly divided into two groups, one having the intravenous catheter removed every 48 hr and the other having the catheter changed only when necessary . One hundred and eighty-seven catheters from 50 patients were cultured . Eleven (5.9%) of the catheters were found to be colonized by organisms . Metal needles and plastic cannulas were infected with similar frequency . The incidence of local infection was not influenced by concurrent antibiotic therpy, local phlebitis, or the level of the granulocyte count during the period of intravenous infusion . Six of 31 catheter tips in place for longer than 56 hr were colonized by organisms, compared with 5 of 156 catheter tips in place for less than 56 hr (p less than 0.0001) . The study indicates that indwelling intravenous catheters should be changed at least every 48 hr in order to prevent colonization of the tip of the intravenous catheter.

Genetika, 1975, 11(11), 67 - 78
{Characteristics of hybrid strains of actinomycetes, prepared by crossing Streptomyces coelicolor A3(2) and Streptomyces lividans 66 strains}; Danilenko VN et al.; Pecularities of crosses between strains of Streptomyces coelicolor A3(2) and S . lividans 66 are described . Recombinants which contain different contributions from parental chromosomes are shown to arise in these crosses . Due to a low frequency of recombination which seems to be the result of incomplete homology between A3(2) and 66 chromosomes, heteroclone and heterokaryone colonies are formed . These may be considered to be intermediate stages in the process of recombinant formation . Results of crosses between A3(2) derivatives of various fertility types are analysed in view of a suggestion that there exist two modes of genetic material transfer in Actinomycetes: by means of conjugation and via heterokaryone formation stage . The study of recombinant properties reveals that in the presence of sex plasmid SCPI F two substances are formed, one of which (IAM) inhibits airial mycelium and the other (ISM)--substrate mycelium growth . In addition, not only SCPI presence but the involvement of certain A3(2) genes seems to be required for ISM synthesis . A part of recombinants is shown to possess some new antibiotic properties differing from those of original parental strains namely extension of their antimicrobic spectrum for Actinomycetes and bacteria.

Antibiotiki, 1975, 20(12), 1081 - 5
{Trichothecene inactivation by proteolytic enzymes from Trichothecium roseum Lk ex Fr}; Maksimova RA et al.; Trichothecium roseum Lk ex Fr produces simultaneously trichothecin and proteolytic enzymes possessing fibrinolytic, thrombolytic and esterase activity . In addition to the function of splitting and consuming the substrate, the proteolytic enzymes of T . roseum are probably able to hydrolize the other bond in the molecule of trichothecin, which results in partial inactivation of the antibiotic in both the fungus culture and the model experiment on trichothecin contact with the preparations of the proteolytic enzymes . Presence of proteases of T . roseum may be considered as a protective mechanism for detoxication of the metabolites toxic for the organism.

Eksp Med Morfol, 1975, 14(3), 161 - 5
{Gentamicin toxicity to animals of both sexes and different ages}; Mangurova M et al.; Gentamycin acute toxicity in sexually-immature and sexually-mature male and female rats was tested comparatively . DL50 for the female sexually-mature rats was found to be statistically reliable lower than that for the remaining three groups of animals . The greatest differences were observed in the values for the maximum non-lethal and minimum lethal doses of this antibiotic . The authors suggeste the use of a new index for the evaluation of gentamycin acute toxicity called Dose Range Index.

Genetika, 1975, 11(6), 180 - 3
{Hybridization in Actinomycetes}; Lomovskaia ND et al.; Ways of transferring genetic information in Actinomycetes and their use for the transmission of genetic material in intervarietal crosses are discussed . The producing of hybrids is shown to be an efficient method to obtain Actinomycetes strains with new properties . Properties of recombinants obtained in intervarietal crosses Streptomyces coelicolor A3(2)XS . lividans 66 are shown to possess new antibiotic properties differing from those of parental strains: they suppress a number of Actinomycetes and bacterial strains which are not affected by parental strains . It is found that at least two groups of genes located on chromosomes of S . coelicolor A3(2) and S . lividans 66 participate in the synthesis of the antibiotic . The obtaining of recombinants between S . coelicolor A3(2) and S . griseus 15 makes possible to select variants which are capable to produce the antibiotic grisine and are resistant to actinophages, specifically attacking S . griseus . Properties of recombinants between S . coelicolor A3(2) and S . griseus 15 make possible to localize on parental chromosomes regions containing genes which control the synthesis of the antibiotic, the formation of a receptor for the adsorption of actinophages, and genes controlling the restriction and t he modification of actinophage development in S . coelicolor and S . griseus . A sex plasmid (SGP1) is found in S . griseus 15.

Neoplasma, 1975, 22(4), 347 - 54
On the influence of chloramphenicol on the induction of lung adenomas by urethane in mice; Shabad LM et al.; It has been shown by a number of authors that the antibiotic chloramphenicol (CP), produced in the USSE under the name of levomycetin, had considerably inhibited the growth of liver tumors, induced by various carcinogenic compounds {3,7,8,21} . Moreover, it has been found by ourselves and other authors that CP greatly reduces the toxic effect of carcinogenic polycyclic hydrocarbons on cultures of embryonic fibroblasts of mice and the adrenals of rats {5,9,20,23} . As the full extent of the antiblastomogenic activity of CP has so far not been studied, it was important to elucidate its influence on other groups of chemical carcinogens . In experiments described in the present paper we have investigated the influence of CP on the incidence of lung adenomas in mice after administration of urethane.

Basic Life Sci, 1975, 5B, 807 - 11
Radiosensitization of a human cell line lacking repair replication; Lee YC et al.; A human cell line has been isolated that is deficient in X-ray-induced repair replication . The slope of the radiation survival curve is greater in the presence of the anthracycline antibiotic, adriamycin . The results suggest that radiosensitization by DNA-binding drugs is more probably related to DNA strand breakage phenomena than to the polymerase step of excision-repair.

Curr Med Res Opin, 1975, 3(6), 392 - 6
Gastro-intestinal absorption and transplacental transfer of amoxycillin during labour and the influence of metoclopramide; Buckingham M et al.; The absorption of amoxycillin from the gastro-intestinal tract, with or without oral metoclopramide, has been evaluated . Levels of amoxycillin in the maternal blood and liquor prior to the induction of labour were of a therapeutic level against many organisms . However, absorption during labour, as reflected by maternal blood levels at delivery and cord blood levels, suggests that amoxycillin is poorly absorbed and may not reach adequate therapeutic levels in the fetus . Oral metoclopramide did not improve the absorption of amoxycillin . Should a parenteral form of amoxycillin become available, a similar study of blood and liquor levels may indicate that, like ampicillin, intramuscular administration is required for adequate therapeutic use at this stage of pregnancy . Until an oral formulation of an appropriate antibiotic is available which gives rapid absorption may and a sustained level of the chemotherapeutic agent in this situation, parenteral administration of an appropriate antibiotic remains mandatory.

Allergol Immunopathol (Madr), 1975 Jan-Feb, 3(1), 1 - 8
Allergic pathogenesis in chronic bronchitis; Businco L et al.; Chronic bronchitis is a disease related to numerous etiologic factors: infections, climate influence, air pollution, cigarette smoking, etc . From a pathogenetic point of view, chronic bronchitis is generally considered as the phlogistic resultant of various irritative conditions, with a characteristic neutrophil component in the phlogistic pattern . Microbic involvement has up to now been considered a very important factor, with consequent wide utilization of antibiotic agents in basic therapy . Considerations of clinical nature induced us to consider unsatisfactory such pathogenetic concepts based on neutrophil phlogosis, while the involvement of an allergic mechanism became more acceptable . In order to solve this problem, we have carried out hitological studies on postmortem material from the respiratory tract of individuals whose death was attributable to chronic bronchitis or to concurrent chronic bronchitis . Results of our study conducted up to now on 60 cases may be summarized as follows: Bronchitis with lymphomonoplasmacytoid phlogosis of immunoallergic type (60%), bronchitis with neutrophil phlogosis of irritative-infective type (20%); bronchitis with mixed allergic-neutrophil phlogosis (20%) . Lymphocytes, monocytes and plasma cells are directly involved in allergic tissue reactions, both of immediate and delayed type because they release active substances such as hsitamine, bradyquinine, quinine, etc., which will their multiple pharmacodynamic actions are responsible of various anatomic and functional changes in hypersensitivity . Infiltration of the bronchial mucosa with lymphomonoplasmacytary cells in chronic bronchitis, has a pattern of mixed allergic phlogosis of immediate and delayed type . Prophylaxis and management of chronic bronchitis should therefore be set up on new bases, with the various treatments used for hyperactive pathology.

Acta Biochim Pol, 1975, 22(3), 257 - 61
Acyl-CoA pool and acyl-CoA thioesterase in Streptomyces noursei var . polifungini; Rafalski A et al.; The size of acyl-CoA pool in S . noursei var . polifungini was found to be associated with the antibiotic-synthesizing ability, and was negatively correlated with both the thio-esterase activity (acetyl-CoA hydrolase, EC 3.1.2.1) and its affinity towards acetyl-CoA and propionyl-CoA . The apparent Michaelis constants with acetyl-CoA and propionyl-CoA were 33 times 10(-5) and 6.6 times 10(-5) M in the low producing strain, and 8.5 times 10(-4) and 1.2 times 10(-4) M in the high producing strain, respectively.

Folia Microbiol (Praha), 1975, 20(2), 97 - 102
Morphogenic effects of ramihyphin A in filamentous fungi; Barathova H et al.; Ramihyphin A at subfungistatic concentrations stimulates ramification of hyphae of filamentous fungi . Stimulation of terminal ramification of hyphae that can be observed particularly in phytopathogenic fungi is most frequent . Hyphae of Microsporon canis, Trichophyton mentagrophytes, Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum ramify intensively laterally . Stimulation of the lateral ramification was observed in Monilia fructigena, Penicillium marneffei and Penicillium chrysogenum . The antibiotic induces also formation of vesicular structures in phytopathogens . Due to the substantial ramification of hyphae, both terminal and lateral, the growth of colonies is interrupted . The addition of the antibiotic to a growing colony of Botrytis cinerea induces dichotomic ramification of terminal hyphae after 3 h of growth . Lateral hyphae begin to grow later and further ramify dichotomically . Dense bundles of ramified hyphae are formed after 24 h due to the unbalanced ramification and the colony no longer increases its size.

Klin Padiatr, 1975 Jan, 187(1), 71 - 80
{The plasma-protein-binding of Clindamycin Cephazolin and Cephradin in neonates and adults (author's transl)}; Kiosz D et al.; In pooled serum of 12 healthy adults and 12 neonates (blood taken from the umbilical cord) the free and protein-bound parts of Cephazolin, Cephradin and Clindamycin were tested by equilibrium dialysis in relation to the concentration of the antibiotic . In the serum of adults at a concentration of 36 mcg/ml the free part of Cephazolin amounted to 16%, at a concentration of 35 mcg/ml the free Cephradin was 87%, at a concentration of 97 mcg/ml the free Clindamycin was 16% . The binding constant k of Cephazolin was 12.0 (rise-constant 0.58), of Cephradin 0.26 and of Clindamycin 15.8 (rise-constant 0.58) . When concentration of antibiotics rose, the free part of Clindamycin and Cephazolin increased more than with Cephradin . At a concentration of 30--42 mcg/ml the differences between the sera of adults and neonates were 26.4% with Cephazolin, 3.7% with Cephradin and 3.1% with Clindamycin (concentration 92--97 mcg/ml) . In neonates the free part of Cephazolin was 43%, of Clindamycin 19% and of Cephradin 90% . The lower ablumin content in serum of neonates (3.7 g%) does not altogether explain the reduced protein-binding . In neonates a different affinity for binding has to be assumed.

Sov J Dev Biol, 1975 Jan, 5(1), 63 - 5
Effect of antimycin A on sensivitivy of fertilized sea urchin egg cells to embryotoxic analogs of serotonin; Buznikov GA et al.; Antimycin A blocks cleavage divisions in concentrations 1-10-15-1-10-14 g/ml (experiments on Arbacia lixula) or 1-10-11-1-10-9 g/ml (experiments on sea urchins of the genus Strongylocentrotus) . Subthreshold and threshold concentrations of this antibiotic do not affect the sensitivity of fertilized Strongylocentrotus intermedius to 1-benzyl-2, 5-dimethylserotonin, but increase their sensitivity to 5-butyltryptamine by a factor of 3-5 . These data provide the basis for a discussion of the possible nature of the reception of serotonin and other low-molecular-weight regulators of early embryogenesis.

Microbios, 1975, 12(50), 209 - 18
Synergism of amphotericin B and 2-deoxyglucose against Histoplasma capsulatum yeasts in vitro; Berliner MD; The glucose analogue, 2-deoxyglucose (2DG), enhances both the fungistatic and the fungicidal action of amphotericin B in Fungizone (Squibb) against Histoplasma capsulatum yeasts in vitro . This synergistic effect is more pronounced when the test substances are incorporated in double-diffusion agar plates than in liquid medium . Minimum inhibitory concentrations for 2DG and amphotericin B in Fungizone have been established . The effects of components of Fungizone other than amphotericin B as clinically administered were also studied . Neither sodium desoxycholate nor phosphate buffer had any effect on the test organisms when used in recommended clinical concentrations . The 5% glucose infusion solution greatly enhanced the growth of the pathogen and markedly decreased the effectiveness of amphotericin B . H . capsulatum yeasts quickly became resistant to stepwise increases of Fungizone but not of 2DG . Susceptibility to amphotericin B and to 2DG increased with time within certain limits of exposure . The A (albino) phenotype of H . capsulatum is considerably more resistant to amphotericin B than the B (brown) phenotype, but there are no differences in susceptibilities to 2DG . The potential clinical applications of these studies are discussed, since experimental animals and man are reported to tolerate large amounts of 2DG . The incorporation of 2DG in the polyene antibiotic preparation would render it more effective at lower doses and would decrease clinical toxicity.

Scand J Infect Dis, 1975, 7(1), 21 - 8
Temporary skin reactions to penicillins during the acute stage of infectious mononucleosis; Andersen Lund BM et al.; During the acute stage of infectious mononucleosis (IM), 16 out of 19 patients have reacted to skin tests with ampicillin and/or benzylpenicillin or their derivatives . Two thirds reacted to ampicillin and less than half (10/19) to benzylpenicillin, or their derivatives . No reaction was observed with cloxacillin . The lack of reactivity in 3 of 7 patients and the circumstance that the frequency of reactions with the penicilloylated Escherichia coli proteins makes it likely that the greater reactivity to penicillins and in particular to ampicillin in IM is not due mainly to protein impurities, but chiefly to the antibiotic molecule as such . There was no definite relationship between reactivity and clinical involvement . After the acute stage, disappearance of skin reactivity was noted . Intracutaneous testing with penicillins may be used to monitor the increased cutaneous reactivity during acute IM, and it may be helpful when the acute stage is over to determine when a patient may use these antibiotics without side reactions.

J Pharm Sci, 1975 Jan, 64(1), 84 - 7
Antitumor agents II: nitrogen analogs of mycophenolic acid; Beisler JA et al.; Mycophenolic acid, a novel antibiotic of low toxicity containing no nitrogen atoms in its structure, induces tumor regression in several murine solid tumor assays . It has been reported in extensive structure-activity studies that chemical modifications on the antibiotic itself reduce or eliminate antitumor activity . With the objective of antitumor activity enhancement, nitrogen-containing analogs of mycophenolic acid were synthesized according to a program directed toward the ultimate synthesis of close bioisosteres of the antibiotic . Intial efforts reported here describe the terpenoid side-chain degradation of N-geranyl-2(1H)-pyridones and N-geranylglutarimides, where the terminal isopropylidene is replaced with a carboxyl group as it occurs in mycophenolic acid . The resulting nitrogen-containing analogs of the antitumor antibiotic were inactive in the l-1210 and Walker 256 tumor systems.

Vet Med Nauki, 1975, 12(2), 23 - 30
{Administration of streptomycin to the uterus by electrophoresis}; Rizo B et al.; Comparative experimental studies on female dogs and rabbits revealed the extent to which the penetration and deposition of streptomycin in the tissues of the uterus, oviducts, mesometrium, ovaries, the blood serum and other organs take place . The antibiotic is applied i/m, via the uterus through electrohoresis following a method developed by the authors and through simple introduction into the uterus . Results have shown that the electrophoretic introduction of streptomycin is advantageous in terms of a readily achieved depot in the tissues mentioned above which remains active at values above the therapeutic concentrations 24 to 48 hours following the application of the antibiotic.

Dis Colon Rectum, 1975 Jan-Feb, 18(1), 22 - 7
Acute obstruction in cancer of the colon and rectum; Kronborg O et al.; Results after operations for acute obstruction of the large intestine due to cancer were analyzed during a 10-year period and compared with the results after operations for nonobstructive tumors during the same period . The following conclusions could be deduced: 1) Cancer is more often obstructive in the colon than in the rectum . Cancers of the splenic flexure are relatively more often obstructive than cancers in other parts of the colon . 2) Postoperative morbidity (and probably mortality) is higher and the five-year survival shorter in patients with obstructive cancers of the large intestine than in those without obstruction . Obstructive Dukes' A tumors are very few . 3) The early morbidity and mortality after acute cecostomy are probably not higher than after acute transversostomy, if the cecostomy wound is left open . The cecostomy carries a risk of peritoneal contamination . 4) Cecostomy does not relieve obstruction in 5-10 per cent of the patients, while transversostomy seems always to be effective . Emergency exploratory laparotomy for obstructive cancer of the large bowel instead of a blind cecostomy reduces the number of patients who need two operations by 10 per cent . 5) Hernias are frequent at the sites of previous spontaneously closed cecostomies . 6) Antibiotic bowel preparation seems not to be effective shortly after decompressive colostomy.

Antibiotiki, 1975 Jan, 20(1), 36 - 40
{Use of a 2-part model of i pharmacokinetics of gentaniycin for maintaining a constant blood concentration in infusion intravenous (an experimental study)}; Solov'ev VN et al.; Maintenance of constant antibiotic blood levels within the required ranges may be accomplished with mathematical modelling of the antibiotic pharmacokinetics . The problem solvation was illustrated on gentamicin . The kinetic analysis of the curves of the drug excretion from the blood after a one-moment intravenous administration of the antibiotic to cats provided estimation of the constants for a two-compartment model of its pharmacokinetics . The constant values were used for calculation of the intravenous infusion rate for gentamicin and the load dose value providing attainance and maintenance of the drug blood levels within the required ranges . The experimental testing of the regiments of gentamicin infusion showed satisfactory correlation of the theoretically supposed and practically found antibiotic blood levels.

Antibiotiki, 1975 Jan, 20(1), 11 - 5
{Formation of organic acids by an active strain of Act . rimosus and by an inactive mutant in relation to oxytetracycline biosynthesis}; Bryzgalova TE et al.; Formation of organic acids by an active oxytetracycline-producing strain and an inactive mutant under conditions favourable (starch medium) and unfavourable (glucose medium) for the antibiotic biosynthesis was studied . It was shown that the active strain practically produced no organic acids on the starch medium . Under conditions unfavourable for the antibiotic biosynthesis the decrease in the activity level correlated with accumulation of marked amounts of pyruvic and lactic acids . The mutant possessing no capacity for the antibiotic biosynthesis produced significant amounts of pyruvic, acetic and lactic acids, the amounts of the acids markedly increased on the glucose medium . By the composition of keto acids the active strain and the inactive mutant did not differ.

Arthritis Rheum, 1975 Jan-Feb, 18(1), 83 - 90
Treatment of septic arthritis: comparison of needle aspiration and surgery as initial modes of joint drainage; Goldenberg DL et al.; Surgery and needle aspiraton have been evaluated as initial modes of drainage in 59 patients with acute septic arthritis . Full recovery was noted in 42% treated surgically at the outset . On the other hand, 67% of those treated by needle aspiration recovered without sequelae, despite the greater prevalence in this group of adverse host factor-eg, serious underlying illness, concommitant extraarticular infection, prior arthritis in the infected joint, and recent antibiotic or immunosuppressive therapy.

Acta Chem Scand B, 1975, 29(6), 662 - 6
Light sensitive chloramphenicol analogues; Nielsen PE et al.; Some chloramphenicol analogues have been prepared in order to find reagents which could be used in a photoaffinity labelling study of the peptidayl transferase center of the E . coli ribosome . The compounds were tested for antibiotic activity in vitro in the "fragment reaction" assay, and for their ability to generate very reactive species upon irradiation.

Mol Gen Genet, 1975, 137(2), 89 - 99
Lomofungin inhibition of allophanate hydrolase synthesis in Saccharomyces cerevisiae; Lawther RP et al.; The RNA polymerase inhibitor, lomofungin has been used to determine the half life of specific synthetic capacities (invertase and alpha-glucosidase) as well as that for gross protein synthesis . In both cases the studies conclude that cognate messenger RNAs decay with a half life of approximately 20 minutes . This antibiotic has been used to determine the half life of allophanate hydrolase specific synthetic capacity . We find that it decays with a half life of about three minutes; a value that agrees with the decay rates of allophanate hydrolase synthetic capacity following removal of inducer . These observations argue that mRNA may be metabolized by two separate routes in Saccharomyces.

Chemotherapy, 1975, 21 Suppl 1, 76 - 90
Doxycycline in respiratory tract infections . Report of a retrospective study in Spain during the winter 1972-1973; Casado MJ; In the winter of 1972-1973 a multicentre trial of the treatment of upper and lower respiratory tract infections was carried out in Spain using doxycycline . 85 physicians participated in the study and treated 1,653 patients . The infections included acute bronchitis, acute exacerbation of chronic bronchitis, pneumonia, bronchopneumonia, tonsillitis, pharyngitis, trachetis, sinusitis, and otitis media . The majority of the patients were adult out-patients although some children and adolescents were included: 1,011 of the patients were male and 642 female . A number of the signs of respiratory infection such as temperature, cough, pain and inflammatory symptoms were examined . A rapid reduction in intensity and severity was noted in all of these parameters . Tolerance to the antibiotic was excellent . Only minor side-effects were reported and these were mild and mainly limited to the gastro-intestinal tract - in no case was treatment discontinued . The total number of side-effects was 37; they occurred in 31 out of the 1,653 patients . The overall evaluation of results showed a very good or good response in 85% of the patients . It appears from this multicentre study that the efficacy of doxycycline has in no way decreased over the 7 years of its extensive use in Spain . It remains a fast acting and effective antibiotic in upper and lower respiratory tract infections irrespective of age, sex or diagnosis.

Chemotherapy, 1975, 21 Suppl 1, 68 - 75
A comparative trial of doxycycline and ampicillin in the treatment of acute sinusitis; Agbim OG; A double-blind comparative clinical trial of doxycycline (200 mg on the first day followed by 100 mg daily for a total of 7 days) and ampicillin (250 mg 4 times daily for 7 days) was performed in 44 patients with acute or chonic sinusitis . Significantly superior results were observed with doxycycline; 90% of the patients responded to doxycycline and 35% to ampicillin . The incidence of side-effects was low and these were of a minor nature, in no case with either drug was discontinuance of treatment necessary . These results imply that in treating chronic bronchitis an antibiotic should be given which is effective not only against the responsible organisms but which is able also to penetrate those tissues (such as the sinuses) that act as a reservoir for these organisms . Doxycycline meets these requirements.

Chemotherapy, 1975, 21 Suppl 1, 58 - 67
Vibramycin in paediatrics . An evaluation of the onset of action and efficacy; Herz G et al.; The effectiveness of and tolerance to doxycycline (Vibramycin, Pfizer) was investigated in a group of 188 children and the radpidity of both subjective and objective improvement was assessed in a second group of 58 children . Doxycycline was found to be very effective . It was possible to analyse the results of treatment in 245 out of the total of 246 patients . Cure was obtained in 168 patients (68.6%) and marked improvement was seen in 59 (24.1%) . The overall success rate was thus 92.7% . 18 patients (7.3%) failed to respond; these either had a history of relapsing infections or were infected with resistant organisms . Doxycycline also proved to be rapid in its effect . Rapid subjective improvement was seen in 48 out of 58 patients (84.2%) and rapid objective improvement in 41 patients (70.7%) . Tolerance to doxycycline was very good . Treatment had to be interrupted in only one out of 246 patients; there were initial gastrointestinal symptoms in 4 patients . Doxycycline showed itself to be a very suitable antibiotic for use in day-to-day paediatric practice.

Chemotherapy, 1975, 21 Suppl 1, 121 - 9
A multi-centre trial of alpha-6-desoxy-5-oxytetracycline (doxycycline); Serembe M; 23 physicians in Italy took part in a multi-centre clinical trial of doxycycline in the treatment of respiratory tract infections . The case records of 290 patients were assessed with respect to both subjective and objective improvement and clinical cure: most patients were considered improved by the third day and cured by the fifth . The recommended dose of doxycycline was 200 mg on the first day and 100 mg daily thereafter; only 11 of the patients had to continue treatment beyond the tenth day . The antibiotic was extremely well tolerated; gastrointestinal side-effects occurred in 10 patients . Overall, 88.6% of the patients achieved a very good or good result.

Zentralbl Bakteriol {Orig A}, 1975, 230(3), 320 - 35
Frequency distribution of S . typhi-murium phage types in various countries; van Leeuwen WJ et al.; The phage type and antibiogram of 5199 S . typhi murium strains from 13 countries and of 4949 strains from The Netherlands was determined . For a number of countries it could be established that types predominating in pigs or calves predominate also in humans in that country . However, the predominant phage types were not the same in the various countries . Type 505 predominated in The Netherlands and, to a lesser degree, also in Belgium and the German Federal Republic . Type 131 predominated in Poland and was also frequently found in the German Democratic Republic . In the German Democratic Republic, type 450 was the most frequently found type . Phage patterns not accepted as a type and occurring one country only, were found to predominate in Italy, Hungary, Israel and Sweden . The majority of antibiotic-resistant strains belonged to a limited number of phage types only.

Antibiotiki, 1975 Jan, 20(1), 45 - 7
{Study of the effect of nystatin and mycoheptin on the intrauterine development of the rat fetus}; Slonitskaia NN et al.; The effect of nystatin and mycoheptyne on pregnancy and fetus of rats of Wister line was studied after single and multiple oral administrations of the drugs . Nystatin was used in single doses of 3000, 500 and 100 mg/kg . In chronic experiments the dose was 500 mg/kg . It was found that nystatin had a slight abortive effect when used during the whole period of pregnancy . Mycoheptyne was used in single doses of 1000, 100 and 20 mg/kg . In chronic experiments the dose was 100 mg/kg . It was noted that mycoheptyne had a higher toxic effect on the pregnant rats than nystatin . The animal death and abortus were observed more often . The level of the changes depended on the dose, time and period of the antibiotic use . No defects in the rat fetus were found.

Vopr Med Khim, 1975 Jan-Feb, 21(1), 13 - 8
{Metabolic stability of the protein-synthesizing system of the myocardium in compensatory cardiac hyperfunction in actinomycin D block of RNA synthesis}; Iavich MP et al.; Under conditions of complete actinomycin block in rat heart muscle an inhibition of protein synthesis and dissociation of myocardial polyribosome structures were observed (half-life was equal to 6.5 hrs) . In compensatory hyperfunction of heart muscle, caused by stenosis of aorta, the inhibitory effect of actinomycin D on the protein synthesis was manifested earlier than in control and was exhibited more distinctly . In myocardium under compensatory hyperfunction of heart muscle the protein synthesis was decreased by 50% within 4 hrs after administration of actinomycin into animals and it was completely inhibited within 10 hrs after the antibiotic administration . The alteration in stability of polyritobosomes under compensatory hyperfunction of heart muscle was specific for myocardium and was not observed in liver tissue.

J Trauma, 1975 Jan, 15(1), 42 - 62
The burn wound from the surgical point of view; Janzekovic Z; The surgical approach cannot, and should not, be different for a mechanical wound and for a burn wound . Thin autografts applied over an excised burn wound act as the best antibiotic and the best analgetic, and at the same time provide a definite cover . The removal of thin skin grafts does not represent any additional danger to the burned patient . Homografts applied on excised dermal surfaces act as the best protection for potentially damaged layers of dermis, assuring spontaneous epithelization after their rejection . The clinical results obtained by primary necrectomies in extensive deep burns justify the conclusion that more of our effects should be concentrated towards an earlier and more adequate treatment in the early postburn phase . I am sure that the only chance of survival of critically burned patients depends on efficient action . Like Evans, I do believe in the value of whole blood transfusion in badly burned patients . We have to try to save their lives by changing their blood, as we do without hesitation in cases of badly matched blood transfusions.

Antibiotiki, 1975 Jan, 20(1), 18 - 22
{Some patterns in the distribution of free and bound monomycin in the organs and tissues of immunized animals}; Danielova LT et al.; Distribution of unbound and bound monomycin in rabbits immunized against paratyphoid fever and colibacteriosis was studied at various stages of the immunization . The studies showed that the immunological reconstruction had a definite effect on the distribution character and the processes of the antibiotic binding in the vaccinized rabbits . The binding processes in the lymphoid cells increased, while those in the parenchimatose cells decreased . The concentration of the unbound and bound preparation in the organs and tissues at the background of the immunity was 2-3 times lower than that in the non-immunized animals . The bone marrow, where it markedly increased was an exception.

Am J Clin Pathol, 1975 Jan, 63(1), 98 - 105
Elevated titers of serum agglutinators . A serologic indicator of infection; Waller MV et al.; Elevated titers of serum agglutinators (anti-FabIgG) are associated with significant and severe suppurative infection . Immunosuppression and long-term antibiotic therapy, however, may lead to negative tests.

Scand J Infect Dis, 1975, 7(2), 153 - 5
Meningitis developing during cephalothin therapy of septicaemia; Freij L et al.; A 63-year-old woman developed pneumococcal meningitis during cephalothin treatment for pneumococcal septicaemia . The poor penetration of this antibiotic over the blood-brain barrier makes it unsuitable for the therapy of meningitis . If cephalothin is used in other serious infections, the patient should be closely observed for the development of meningitis.

Chemotherapy, 1975, 21 Suppl 1, 130 - 5
Doxycycline in respiratory tract infections . A review of a multi-centre trial; Meier J; A total of 256 patients were admitted in Germany into a Pan-European multi centre trial of doxycycline in the treatment of infections of the respiratory tract . The diagnoses showed a preponderance of lower respiratory tract infections compared with other European countries, due largely to the fact that the participating physicians were pulmonary or internal medicine specialists . Doxycycline was given in a dose of 200 mg initially followed by 100 mg daily for 5-10 days (only the occasional patient varied from this regimen) . Side-effects were uncommon (2.5-3.5%) and affected only the gastrointestinal tract . Four patients had to change antibiotic therapy, not because of side-effects but because of possible bacterial resistance in these patients . The results were comparable with those from the rest of Europe: 88% of patients had a good or very good response . Nine patients were treated for longer than 14 days and only eight patients did not show improvement.

Antibiotiki, 1975 Jan, 20(1), 53 - 8
{Study of oxytetracycline solubility in an aqueous medium}; Lin'kov GI et al.; Solubility of oxytetracycline dihydrate in aqueous media was studied . It was shown that solubility of the drug in bidistillate at a temperature of 20 degrees was 195 gamma/ml, which was much lower than the requirements of some pharmacopoeia with respect to the drug solubility . Dependence of oxytetracycline dihydrate solubility in the aqueous medium on the values of pH and temperature was found . Indigency of the procedure described in the literature for determination of antibiotic solubility according to the dry weight of the filtrate on addition of large excesses of the solid phase to the system was shown.

Vopr Onkol, 1975, 21(6), 112 - 6
{The damaging effect of the sodium salt of nystatin on ascitic tumor cells}; Zhubanova AA et al.; The experiments in vitro have demonstrated that an application of 0.1 mg/ml of nistatine into ascitic cells suspension would result in swelling of cells and 80% loss of intracellular potassium, associated with a considerable reduction of Na+K+-ATP-ase activity, the intensity of respiration and glycosis being changed but insignificantly . Thus, the influence of a polyene antibiotic - nistatine on the water-salt balance of ascitic cells under study is likely to be somewhat related with inhibition of NA+K+-dependent ATP-ase.

Antibiotiki, 1975 Jan, 20(1), 66 - 71
{Experimental effect of bruneomycin on the energy metabolism of liver tissue}; Gol'dberg ED et al.; The effect of an antitumor antibiotic bruneomycin on the energy metabolism in the liver tissue was studied . Four hours after the drug administration the consumption of glycogen and glucose in the liver tissue increased because of glycogenolysis activation, which was evident from increased activity of prosphorylase, phosphofructokinase, hexokinase and summation glycolytic activity . 24 and 48 hours after the antibiotic administration the balance of consumption and resynthesis of phosphate macroergs in the liver tissue impaired, which was evident from decreased levels of ATP, impairement of conjugation of the processes of oxidation due to impairement of permeability and structural integrity of the mitochondrial membranes . Further decrease in the glycogen liver levels was mainly due to suppressed resynthesis of glycogen because of destructive-necrotic processes . Simultaneously the processes of glycolytic splitting of glucose decreased which was evident from decreased activity of the enzymes and summation glycolytic activity.

Int Ophthalmol Clin, 1975 Winter, 15(4), 19 - 35
Diagnosis and management of herpes simplex ocular infection; Pavan-Langston D; The multifaceted nature of ocular herpes simplex has become more clearly defined in recent years, as it has become apparent that it is a disease characterized by both infectious and immune components . Therapy Therapy of infectious epithelial dendritic-geographic disease is generally gentle debridement of the ulcer followed by antimetabolite chemotherapy with IDU or Ara A . Tropic (metaherpetic) ulceration may occur postinfection and is caused by sterile basement membrane damage, which makes it difficult for the epithelium to heal across the damaged ulcer base . Therapy is generally that of recurrent erosion and involves patching, soft contact lenses, and lubricating drops and ointments . Stromal disease may be (1) viral interstitial keratitis, which is slowly responsive to antiviral therapy, or (2) immune disciform reaction, which may or (hopefully) may not necessitate steroid therapy with prophylactic antiviral and antibiotic cover . Herpetic iritis may occur alone or with any form of corneal disease . While it is generally felt to be caused by intact intraocular virus, therapy is still steroid-oriented for lack of more effective and penetrating antiviral drugs . Antimetabolite-induced medicamentosa may mimic almost any form of herpetic disease and should be ruled out in any differential diagnosis of a patient deteriorating under therapy.

Z Mikrosk Anat Forsch, 1975, 89(2), 319 - 26
Effect of streptozotocin on the blood glucose level and histology of the principal islets of Channa punctatus (Bloch); Gill TS et al.; The effect of streptozotocin, an antibiotic and diabetogenic drug, has been studied on the blood glucose level and islet histology of a freshwater fish, Channa punctatus . The drug elicits a triphasic response in the blood glucose level, comprising an initial hyperglycemia followed by a transient fall, and restitution of normal values 3...4 days after the treatment . Significant degenerative changes occur in the islet beta cells . Severity of the beta cell damage is dose dependent and the drug has been found to be beta-cytotoxic to a considerable extent . Unlike mammals, Channa punctatus does not become diabetic following the streptozotocin administration, at doses varying 200-400 mg/kg b.wqnd over a period of 96 hours post-injection.

Bibl Haematol, 1975, (40), 27 - 43
Progress in the chemotherapy of hematologic diseases; Frei E 3rd; Progress in the chemotherapy of Hodgkin's disease and experimental therapeutic, pharmacologic, and clinical studies of the antitumor antibiotic, adriamycin, are presented in this abstract . In patients with disseminated Hodgkin's disease, the combination chemotherapy program (MOPP) produces a significant increase in the complete remission rate . This has been increased to 90% by the addition of low dose bleomycin to the MOPP program . The continuation of MOPP treatment beyond 6 months and to a total of 24 months provides improved results in patients in remission as measured either from time of onset of complete remission or from end of treatment . Finally, the pattern of relapse in patients with Hodgkin's disease provides a rationale basis for the selective use of radiotherapy in patients in complete remission . Adriamycin has a broad spectrum of antitumor activity in man . Its mechanism of action involves intercalation with DNA and inhibition of DNA function . The selective effect against tumors is not understood but may relate to membrane transport . Adriamycin is a highly important new antitumor agent for the treatment, not only of hematologic malignancies, but for a variety of solid tumors as well.

Acta Derm Venereol, 1975, 55(2), 135 - 40
Lipo-atrophy of the ankles and its relation to other lipo-atrophies; Jablonska S et al.; Two typical cases of lipo-atrophy of the ankles are described, one case of atrophy of the ankles with associated atrophy of the whole extremity, and one case of localized atrophy of the knee . For comparison, we present one case of atrophy in a diabetic patient due to insulin injections but developing at distant sites, and in one case, a child in whom atrophy followed antibiotic injections . Primary inflammatory vascular changes in the subcutaneous tissue were demonstrated in atrophy of the ankles, as in the early period of insulin-induced lipo-atrophy . Attention is called to the possible relation of the described lipo-atrophies.

Acta Biochim Pol, 1975, 22(4), 311 - 7
Non-specific acetyl-CoA carboxylase and methylmalonyl-CoA carboxyltransferase in Streptomyces noursei var . polifungini; Rafalski A et al.; 1 . Acetyl-CoA carboxylase (EC 6.4.1.2) and methylmalonyl-CoA carboxyltransferase (EC 2.1.3.1) have been isolated from mycelia of Streptomyces noursei var . polifungini, and purified about 50-fold . 2 . Both enzymes carboxylate acetyl-CoA and propionyl-CoA; the respective Km values are 1.1 and 1.6 mM with acetyl-CoA carboxylase and 2.5 and 1.25 mM with carboxyltransferase . 3 . The activities of both enzymes are inhibited by free fatty acids . Almost total inhibition of methylmalonyl-CoA carboxyltransferase was observed by 0.1 mM-butyrate or 0.1 mM-C14-C18 acids . Acetyl-CoA carobxylase was affected to the same extent by these compounds at concentration of about 1 mM . 4 . The role of both carboxylating enzymes is biosynthesis of the antibiotic is discussed.

Magy Traumatol Orthop Helyreallito Seb, 1975, 18(4), 286 - 91
{Infectious complications of primary osteosynthesis in aged patients}; Andras G et al.; In respect of iatrogenic infections the elderly patients are to be considered as endangered . Modern traumatology increases this danger in consequence of the foreign materials placed in the wounds . The role of the antibiotic and chemotherapeutic prophylaxis is of utmost importance . Regrettably, the resistance of the pyogenics, especially of the strains in the hospitals is increasing, - in consequence, besides the maximal sterility the further improvement of the surgical technique and of the after-treatment are the most important tasks . In the case of infection aimed antibiotic and chemotherapeutic, resp., treatment may be successful.

Rev Inst Antibiot (Recife), 1974 Dec, 14(1-2), 9 - 16
{First observations on the topical use of Primin, Plumbagin and Maytenin in patients with skin cancer}; Melo AM et al.; Eleven cases of patients bearing basic cellular carcinoma, and one case of patient bearing Kaposi's sarcomatosis, all treated with antibiotics isolated by Goncalves de Lima and Co-workers at the Instituto de Antibioticos, are presented by the authors . Primin, an antibiotic extracted from a vegetal named Miconia sp . (Herb . I.A.-1903) with a 2-metoxi-6-n-pentil-p benzoquinone structure, presented a strong antineoplastic action in the cases treated . Plumbagin isolated from Plumbago scandens in local use, was responsible for a complete healing of the injuries treated . Maytenin extracted from Maytenus sp . (Herb . I.A.-1750) showed less activity than the two previous mentioned, but with a low irritant action and late antineoplastic properties . The authors are going on these experiments . They believe that these antibodies, in local use, may advantageously substitute the surgery and the radiotherapy, meanly in those external ear tumidities and back of the nose, owing to a hurtful action in cartilage, provoked by radiotherapy.

Gynecol Oncol, 1974 Dec, 2(4), 441 - 5
Stagnant loop syndrome resulting from small-bowel irradiation injury and intestinal by-pass; Swan RW; Stagnant or blind-loop syndrome includes vitamin B12 malabsorption, steatorrhea, and bacterial overgrowth of the small intestine . A case is presented to demonstrate this syndrome occurring after small-bowel irradiation injury with exaggeration postenterocolic by-pass . Alteration of normal small-bowel flora is basic to development of the stagnant-loop syndrome . Certain strains of bacteria as Bacteriodes and E . coli are capable of producing a malabsorption state . Definitive therapy for this syndrome developing after severe irradiation injury and intestinal by-pass includes antibiotics . Rapid symptomatic relief from diarrhea and improved malabsorption studies usually follow appropriate antibiotic therapy . Recolonization of the loop(s) with the offending bacterial species may produce exacerbation of symptoms . Since antibiotics are effective, recognition of this syndrome is important . Foul diarrheal stools should not be considered a necessary consequence of irradiation injury and intestinal by-pass.

Rev Inst Antibiot (Recife), 1974 Dec, 14(1-2), 73 - 82
{Taxonomic observations on Streptoverticillium griseocarneum}; De Morais JO et al.; A strain of Streptoverticillium (IA-7527) which produces an antibiotic complex formed at least by two substances--one active against fungi and another active against bacteria--has been identified as Stv . griseocarneum . The methods and the results of the International Streptomyces Project were used . By comparing the results obtained, i.e., the description of the sample IA-7527, with ISP standard descriptions of the related species, and attributing percentual values of similarity to each corresponding item, the overall similarity between the strains compared was obtained . The main result of the study is the conclusion that the ISP descriptions of STV . EHIMENSE, Stv . kentuckense, Stv . mashuense, Stv . parvisporogenes, Stv . takataense and Stv . griseocarneum are so similar, that the cited species--and the strain ISP-5464, IMRU 3631, labeled Stv . rubireticuli--should be considered as synonyms of Stv . griseocarneum, the first species described in the group.

Am J Obstet Gynecol, 1973 Apr 15, 115(8), 1157 - 8
Tuboovarian abscess and the intrauterine device (Majzlin Spring); Duckman S et al.; PIP: 2 case histories of severe pelvic infection and tuboovarian abcesses associated with use of the Majzlin Spring intrauterine device are presented . A 30-year-old parous white woman and a 25-year-old parous black woman were admitted to the Brooklyn-Cumberland Hospitals on separate occassions with a history of prolonged fever, diarrhea, pelvic pain and vomiting . After failure of antibiotic therapy, exploratory laparotomies revealed severely infected ovarian cysts and tuboovarian abscesses with the Majzlin Spring device deeply implanted in the endometrium . Total abdominal hysterectomies and bilateral salpingo-oophorectomies were performed . Although preexisting disease conditions could have existed in these women before the IUD insertion, a cause-and-effect relationship between the IUD as a carrier of a superimposed infection and these conditions should be considered . Much greater care should be taken in the insertion, re-insertion, and follow-up of these devices .

Int J Fertil, 1973, 18(3), 156 - 60
Serious pelvic infections associated with intrauterine contraceptive device; Golditch IM et al.; PIP: A study undertaken to discover whether the incidence and types of intrauterine bacterial growth in IUD users differed from those in nonusers is described . The study 1)compared the early development of infection in IUD users and nonusers, and 2) looked for a correlation between known serious pelvic infection and IUD use . Of 235 patients seen for gynecologic examination (131 IUD users and 104 nonusers), 21 users for 6 months or more and 1 user for less than 4 months had foul-smelling leukorrhea, irregular bleeding, or both . Endometrial cultures were positive in 67% of users, and in 62% of the nonusers . 11 long-term IUD users more than 6 months and 1 nonuser had anaerobic organisms (p less than .01) . Of 31 patients admitted for tubo-ovarian or pelvic abcesses, 17 were IUD users, of whom 9 required hysterectomy . Earlier recognition of foul-smelling mucoid discharge on the IUD tail, or abnormal bleeding, or both, as a sign of early pelvic infection, followed by removal of the IUD and institution of appropriate antibiotic therapy, might prevent the more serious sequelae of pelvic inflammation .

J Pediatr, 1971 Nov, 79(5), 760 - 7
Carbohydrate intolerance in infants with diarrhea; Lifshitz F et al.; PIP: Hospitalized infants suffering from acute diarrhea were used to test simple bedside methods of determining reducing substances and pH in multiple fresh stool specimens . 332 infants were tested, and thetests were useful in detecting a reduced capacity to tolerate lactose in 77% of these patients . Lactose intolerance was considered to be present when the stools had a carbohydrate content greater than .25% and/or a pH of less than 6 . 75 of 77 lactose-tolerant patients recovered within 3 weeks of administration of a milk formula, whereas 111 of 195 with mild intolerance and 13 of 60 with severe lactose intolerance recovered while receiving the milk formula . Diarrhea of greater than 3 weeks duration occurred in 27% of those cases with mild and in with untreated severe intolerance; however, with prompt dietary treatment, a 62% of those cases favorable response always occurred . Lactose intolerance was positively correlated with increased severity of malnutrition; there were no correlations with previous episodes of gastroenteritis, with presence of enteropathogens or with associated infections . When antibiotic therapy was instituted, the stool pH increased toward alkaline, but the excretion of carbohydrates was not modified .

J Urol, 1971 Apr, 105(4), 531 - 3
On the etiology of epididymitis; Wolin LH; PIP: An exceptionally high frequency of acute epididymitis has been observed among military recruits in basic training . 28 soldiers presenting with an episode of acute tender swelling of the epididymis were evaluated . Average age was 21 years . 8 patients reported gonorrheal infection within the preceding 2 months . None had a recent history of trauma or prior operation, and no systemic symptoms or upper respiratory infections were noted . Acute tubular destruction with some micro abscesses in the tubules and some degree of interstitial inflammation was observed in 13 of the 24 cases for which laboratory specimens were adequate . Polymorphonuclear leukocytes were the predominant cells and some cases showed vasculitis . In 8 of the specimens with no tubular involvement, a chronic type of interstitial inflammation was noted . Lymphocytes were the main cells found in these cases . Testicular tissue was normal in 8 patients . Depressed spermatogenesis was noted in 20 patients, 9 of whom manifested inflammation . All viral and culture studies were negative . It was concluded that acute epididymitis is not caused by any culturable bacteria or virus; however, a chemical etiology is possible . Epididymitis appears to be mainly a disease of people who have extended periods of unaccumstomed strenuous physical exertion . Reflux up the vas deferens, induced by the physical strain of basic training, may be a major cause of the high rate of acute epididymitis observed among military recruits . Gonorrhea may also be a contributing factor . Antibiotic use is recommended in such cases to prevent secondary testicular atrophy .

Adv Nephrol Necker Hosp, 1971, 1, 207 - 30
Factors influencing immediate prognosis in acute renal failure, with special reference to prophylactic hemodialysis; Kleinknecht D et al.; Five hundred patients with acute renal failure were admitted to the Department of Nephrology of Necker Hospital between 1966 and 1970; 279 of them were treated before and 221 after beginning systematic prophylactic hemodialysis . The frequency of complications and the survival rate between both groups were compared . No significant improvement was obtained in patients with severe pre-existing diseases or extensive extrarenal lesions; such patients usually died from nonuremic complications before, or despite, dialysis . However, adequate treatment of severe septic shock, when present, was an important factor in improving the immediate outcome . Early and frequent dialysis significantly reduced the frequency and intensity of uremic symptoms such as gastrointestinal hemorrhage . The mortality due to gastrointestinal bleeding decreased from 14% before to 5% after prophylactic hemodialysis . The number of deaths due to septicemia was also substantially lowered from 24 to 12% . Overall mortality was reduced from 42 to 29% . The mortality rate decreased significantly in all categories of patients, particularly in surgical cases (from 54 to 38%) and in traumatic cases (55 to 33%) . Simultaneously, the better use of antibiotic therapy, better prophylaxis of sepsis, and better nutritional care were important factors in the overall improvement in prognosis.

Medicine (Baltimore), 1969 Nov, 48(6), 475 - 91
Tropical sprue in expatriates from the tropics living in the continental United States; Klipstein FA et al.; The results of clinical, laboratory and therapeutic observations conducted over a seven year period in 40 expatriates from the tropics who presented in New York City with overt tropical sprue have been described . The majority of subjects presented with symptoms referable to the gastrointestinal tract, weight loss and weakness . Only nine were symptomatic at the time of arrival; the remainder developed symptoms within several months to 14 years after arrival . Thirty-five subjects had a megaloblastic anemia; this was a secondary to a combined deficiency of folate and vitamin B12 in 25 and to deficiency of only one of these vitamins in the other ten . Serum concentrations of albumin, calcium, and cholesterol were subnormal in approximately one-half and the serum carotene concentrations were low in all but two subjects . Serum values of one or more immunoglobulin were reduced in 19 . All 40 subjects had malabsorption of xylose; 12 of 19 tested had malabsorption of a pharmacologic dose of folic acid; 27 of 28 tested had malabsorption of vitamin B12; and 23 of 27 persons tested had steatorrhea . Jejunal morphology was abnormal in 34 of 35 subjects biopsied prior to treatment; villi were completely absent in four and showed changes of moderate severity in 30 . Treatment with pharmacologic doses of folic acid or vitamin B12 produced a clinical remission in 18 of 21 patients . This remission was sustained in all 14 subjects who were followed for periods of from one to four years and reevaluation of intestinal morphology and function in nine showed improvement in all, but return to normal in less than one-half . Treatment with oral tetracycline for three weeks resulted in clinical improvement in 11 of 12 subjects, a hematologic response in nine of the ten cases who had a megaloblastic anemia, increased absorption of xylose and cessation of steatorrhea in all, and improved jejunal morphology in 11 . Vitamin B12 absorption remained subnormal in nine . Continued antibiotic therapy for six months in eight patients was associated with additional weight gain, further improvement in jejunal morphology and xylose absorption in all, and return of vitamin B12 absorption to normal in all except one . Fifty asymptomatic expatriates from the West Indies were surveyed for abnormalities of intestinal function . The absorption of xylose was reduced in six (24%) of 25 subjects who had been resident in a temperate climate for less than one year but in only one (4%) of 25 persons who had been away from the tropics for more than a year.(ABSTRACT TRUNCATED AT 400 WORDS)

N Engl J Med, 1969 May 8, 280(19), 1058 - 60
Use of drugs and intrauterine devices for birth control; Meeker CI; PIP: The current use of oral contraceptives and intrauterine devices for population control is reviewed including the mechanism of their antifertility actions and the use-effectiveness of each method . The use-effectiveness of the IUD has been calculated as 1.5-3.0 pregnancies per 100 woman-years of exposure . The IUD has a high continuation rate (70% after 2 years) and is excellent for poorly motivated population groups . The most serious common side-effect--pelvic infection--can be controlled by more careful screening and modern antibiotic therapy . Other side-effects include irregular bleeding and uterine perforation, but not at significantly high levels . Oral contraceptives have been found to be virtually 100% effective, even in the new lower dose preparations containing around .5 mg progesterone and .05-.15 mg estrogen per tablet . New hormonal contraceptive approaches include pills which progesterone only, high postcoital estrogen administration, and long-acting injectable progestogen (Depo-Provera) . All of these methods are highly effective but have some undesirable side-effects and require further study . Careful examination of the recent research reports connecting oral contraceptive use with increased risk of thromboembolism indicate that whatever the danger in oral contraceptive use, the direct physical hazards of pregnancy after contraceptive failure are much higher and more serious . Though a 100% safe contraceptive is a desirable ideal, the safety of current oral contraceptives and IUDs is higher than most other aspects of modern life .

Am J Obstet Gynecol, 1966 May 1, 95(1), 46 - 54
Septic abortion; Moritz CR et al.; PIP: 118 cases of septic abortion, including 9 cases of septic shock, are reviewed; no deaths were reported . Of those patients with septic shock, 2 had positive blood cultures (E . coli), 4 had negative cultures, and 3 did not have blood work . A logical plan of diagnosis and management is outlined which emphasizes early diagnosis and institution of massive intravenous broad spectrum antibiotic therapy in all cases, conservative afebrile evacuation of infected uterine contents, and no vasopressor or corticosteroid drugs . An addendum shows 22 more admission for septic abortion; 18 were treated by the described regimen, and 1 case developed septic shock . All cases were discharged alive and well, bringing the total to 130 cases of septic abortion including 10 cases of septic shock with no deaths .






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