Experimental study of the action of the antitumor antibiotic reumycin on the macroorganism]

The side effect of reumycin, an antitumor antibiotic was studied experimentally. The average lethal dose for mice and rats on intravenous administration of the drug was 45.5 and 42.2 mg/kg respectively. When reumycin was administered to rats and dogs for prolong periods of time, an increase in the levels of total protein, urea nitrogen and inorganic phosphorus in the blood was observed, while the levels of hemoglobin and thrombocyte counts decreased, the process of the blood coagulation being slower. The changes in the ECG were similar to those observed in the myocardium dystrophy. The morphological changes in the organs were characterized by perivascular edema, swelling of the vessel walls and edema of the interstitial tissues.     

Differential Antibiotic Excretion in Unilateral Structural Pyelonephritis

Differential antibiotic excretion studies in eight patients with unilateral structural pyelonephritis showed that in all instances there was impairment in antibiotic excretion on the affected side compared with the normal kidney. Both peak and mean urinary concentrations were decreased on the structurally abnormal side. The degree of defect in antibiotic concentration was proportional to the amount of unilateral medullary damage, as measured by differential renal function studies. While the antibiotic concentrations achieved had an inconsistent relationship to cure in three patients with proven unilateral infections, the striking decreases in urinary antibiotic levels may argue against oral penicillin-G treatment of unilateral pyelonephritis in which there is renal parenchymal damage.     

Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults

Objectives: To assess whether antibiotic treatment for acute cough is effective and to measure the side effects of such treatment. Design: Quantitative systematic review of randomised placebo controlled trials. Data sources: Nine trials (8 published, 1 unpublished) retrieved from a systematic search (electronic databases, contact with authors, contact with drug manufacturers, reference lists); no restriction on language. Main outcome measures: Proportion of subjects with productive cough at follow up (7-11 days after consultation with general practitioner); proportion of subjects who had not improved clinically at follow up; proportion of subjects who reported side effects from taking antibiotic or placebo. Results: Eight trials contributed to the meta-analysis. Resolution of cough was not affected by antibiotic treatment (relative risk 0.85 (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re-examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic were more common in the antibiotic group when compared to placebo (relative risk 1.51 (0.86 to 2.64)). Conclusions: Treatment with antibiotic does not affect the resolution of cough or alter the course of illness. The benefits of antibiotic treatment are marginal for most patients with acute cough and may be outweighed by the side effects of treatment.

Key messages

• Acute cough, with or without sputum, is a common reason for consulting a general practitioner
• Although antibiotic treatment is common for this condition, its likely benefits and side effects have not been measured
• This systematic review reports the outcome of nine randomised controlled trials that compared antibiotic with placebo in patients with acute cough
• Resolution of cough and clinical improvement at follow up was no different in the two groups
• The benefits of antibiotic treatment seem to be marginal for most patients with acute cough and may be outweighed by the side effects of treatment

     

Differentiation of the degree of bioavailability of peroral drug forms of tetracycline hydrochloride in experiments on laboratory animals]

Difference in the levels of bioavailability of 4 types of tetracycline hydrochloride tablets was shown on rabbits and guinea pigs. The rates of the antibiotic absorption into the blood of the laboratory animals and volunteers were the same. Relation between the rate of disintegration of various types of tablets of tetracycline hydrochloride and the antibiotic blood levels in the rabbits after administration of the same tablets was found.     

Gentamicin level in the prostate and its pharmacokinetics in patients with benign prostatic hypertrophy]

The study involved 15 male patients with periurethral prostatic adenoma without complete anuresis. The patients were given 80 mg of gentamicin intramuscularly one day before surgery and 80 mg in a one-hour infusion immediately before an operation. Gentamicin blood concentrations were measured. Pharmacokinetic parameters were calculated and dosage schemes for each patient basing on the antibiotic blood levels. Gentamicin levels in removed adenomas were also determined. Adenomas weighed between 18.0 and 45.8 grams while gentamicin concentration ranged from 1.31 to 3.8 micrograms/mL. It was found that gentamicin concentration in adenomas depend upon their weight. Moreover, pharmacokinetic parameters of this antibiotic exert negligible effect on its levels in adenoma.     

Study of the Use of Lincomycin Aerosols in Dogs

This paper reports studies on different aspects of the administration of lincomycin by aerosol in dogs.The purpose of the study was to determine the depth of penetration of the drug into the lungs and its transfer into the blood, urine and tissues when administered as an aerosol.Special consideration was given to the possibility of side effects at the level of the bronchial mucosa, since this study was viewed as preliminary to the use of the antibiotic in humans.     

移植BMSCs对乳腺炎大鼠血清中自由基和抗氧化酶水平变化影响的研究

目的：探讨乳房基底部移植大鼠骨髓间充质干细胞（BMSCs）对实验性乳腺炎大鼠血清中自由基和抗氧化酶水平变化的影响。方法：将70只SD雌性大鼠,其中的60只随机分为3组：对照组、抗生素组和移植BMSCs组,每组20只。通过乳头管灌注内毒素的方法建立实验性大鼠乳腺炎模型,对照组基底部注射生理盐水;抗生素组基底部注射抗生素（5000 U/侧）;移植BMSCs组乳房基底部移植BMSC 50μL（1×106个）,试验0 d时灌注内毒素,1 d时注射BMSCs、抗生素及生理盐水,-1、0、3、5、7 d分别采血样,制备血清,检测血清中丙二醛（MDA）、一氧化氮（NO）、超氧化物歧化酶（SOD）、谷胱甘肽氧化还原酶（GSH-Px）、过氧化氢酶（CAT）水平。结果：移植BMSC组能显著降低乳腺炎大鼠血清中7 d时MDA、NO水平（P〈0.05）,且MDA水平显著低于抗生素组（P〈0.05）;移植BMSCs组7 d时血清中GSH-Px水平和1、3、5 d时CAT水平显著高于对照组和抗生素组（P〈0.05）。结论：BMSC能显著降低乳腺炎大鼠血清中后期NO和MDA水平,提高血清中前期CAT和后期GSH-PX,从而提高机体清除自由基的能力。     

Side effects of antibiotics in patients with thermal burns]

The possibilities of antibacterial therapy in the clinics of burn diseases has at present decreased because of increasing microflora resistance to antibiotics. This phenomenon is one of the most often causes of antibacterial drug side effects in burn patients. For control of infections complications in burn patients which are most often lethal it is necessary to use biologically active subtance, such as prodigiozan and lysozime in addition to the directed antibiotic therapy. The use of specific antitoxic antistaphylococcal drugs, such as antistaphylococcal plasma and antistaphylococcal gamma-globulin in combination with the antibiotics of the direct action provided effective control of infectious complications and sepsis of staphylococcal genesis in burn patients. Decamine proved to be effective along with the usual use of nystatin in cases with dysbacteriosis as a result of the antibiotic side effects. In the patients treated with decamine the sings of candidosis disappeared by the 5th--7th day. Therefore, for decreasing the side effects of antibiotics in the clinics of burn patients it is expedient to use antibiotics in combination with the biologically active and immune preparations which increases the efficacy of antibiotic therapy, impfoves the treatment results and decreases the antibiotic side effects.     

Bioavailability of tetracycline hydrochloride capsules (an in vivo study)]

Blood absorption of tetracycline hydrochloride of various dispersity levels from capsules containing tetracycline alone or in combination with additives, such as magnesium carbonate and calcium salts was studied on humans. It was found that higher dispersity levels of tetracycline hydrochloride powder in capsules was not accompanied by increased blood absorption of the antibiotic. Addition of magnesium carbonate and calcium salts to the antibiotic in the process of capsulation markedly retarded the blood absorption. Clear correlation between the antibiotic dissolution rate in vitro and intensity of its blood absorption in volunteers was shown.     

Use of florfenicol in non-human primates

Studies were undertaken to determine if florfenicol, an antimicrobial agent structurally similar to chloramphenicol, could be used as an effective broad spectrum antibiotic for the treatment of bacterial infections in primates. Florfenicol was developed as an injectable antibiotic for use in cattle on an every other day dosing schedule. Its broad spectrum activity, long duration of action following i.m. administration, and its safety as compared with chloramphenicol made it an attractive antibiotic for use in non-human primates. Previous studies had shown that florfenicol is effective against common primate pathogens such as Salmonella, Klebsiella, Escherichia coli, Bordetella bronchiseptica, Streptococcus pneumoniae, Staphylococcus spp., and Yersinia pseudotuberculosis. We performed experiments on a total of 15 macaques. The animals were given florfenicol at 50 mg/kg i.m. and blood samples taken at various time points. Serum was evaluated for florfenicol absorption. Necropsies were also performed to determine if major organs were affected and to determine the effects of i.m. injection of florfenicol. We determined that florfenicol given every 48 hours in rhesus macaques results in blood levels that were acceptable for therapeutic use. The effect on muscle tissue of i.m. injection was similar to ketamine and normal saline. There were no gross lesions observed and no changes with tissues submitted for histology. Our work shows that with further studies, florfenicol may be useful when injectable antibiotic therapy is required in non-human primates.     

Evolving Roles of Probiotics in Cancer Prophylaxis and Therapy

In nutraceutical science, the ingestible live microbes ‘probiotics’ are regarded for their ability to confer multiplicity of health benefits on the consumers. Wide spectrum impact of these friendly microbes on the host health has been proved very frequently. They have been confirmed to boost immunity, aid in digestion, eliminate pathogens, curb inflammatory bowel diseases, moderate side effects of antibiotic therapy, lower cholesterol and blood glycemic index and produce vitamins. This review, however, focuses on the incipient, but promising area of probiotic diet-based prevention and remedy of cancer. Researchers are in universal agreement with the critical role of probiotics in getting rid of mutagens, delaying the onset of tumors, alleviating the side effects, pepping up chemotherapy, easing the postoperative complications, foiling remission and lifting the spirit of survivors. The key findings in the emerging roles of probiotics in onco-care have been summarized; the biological pathways discussed and anticipated developments in coming times are presented.     

Pharmacokinetic prediction of the efficacy of using sisomicin in wound infections

The pharmacokinetics of sisomicin in the blood, infection foci and urine of patients with wound infections was studied comparatively. Higher blood levels of the antibiotic after intravenous injection as compared to those after intramuscular injection provided its more intensive penetration into the tissues of the wound edges and bottom. After intravenous injection the sisomicin concentration in the tissues was sufficient for inhibition of the strains of Staphylococcus, E. coli and Ps. aeruginosa detected in the patients, while after intramuscular injection the antibiotic levels were sufficient only for inhibition of the first two causative agents. Comparison of the data on the sisomicin pharmacokinetics in the blood and tissues of the wounds provided the characteristics of the level of the drug penetration into the focus of the infection ("therapeutic availability"). Since the levels of sisomicin in the blood and infection foci were highly variable in different individuals. It is recommended that the antibiotic be used under the control of its concentrations in patients. It was shown that the data on the sisomicin renal excretion might be used for the purposes of the pharmacokinetic control.     

Effect of a modified terrilytin on ampicillin pharmacokinetics in experimental peritonitis

The effect of modified terrilytin, a new enzyme of the microbial origin on the pharmacokinetics of ampicillin in experimental peritonitis was studied on 16 pubertal rabbits. Peritonitis was caused by laparotomy and administration of a 15 per cent fecal suspension into the abdominal cavity. The drugs were injected intramuscularly: the enzyme in a dose of 5 PU/kg and the antibiotic in a dose of 10 mg/kg. The ampicillin levels in the blood and peritoneal exudate were determined with the agar-diffusion method. The specimens were collected 30 minutes, 1, 1.5 and 2 hours after administration of the drugs. The animals were divided into 2 groups: control (not treated with the enzyme) and experimental. An increase in the antibiotic levels in the blood and peritoneal exudate by 50--54 per cent was observed. The maximum increase was recorded 30 minutes after simultaneous administration of the drugs.     

Pharmacokinetics of rifamycin

Rifamycin pharmacokinetics was studied on experimental animals after the antibiotic administration by various routes. Parenteral use of the antibiotic resulted in its high levels in rats and rabbits. Irrespective of the administration route, i. e. intravenous, intramuscular or oral rifamycin satisfactorily penetrated into the rat tissues. The highest antibiotic levels were found in the animal liver. In small amounts the antibiotic was excreted with the urine (about 6 per cent for 4 hours). The extrarenal clearance of rifamycin was lower than the plasmic clearance only by 3 per cent and higher than the kidney clearance almost by 40 times. Rifamycin was bound in close amounts by the blood serum of humans, oxen and rabbits, i. e. by 68, 64 and 56 per cent respectively. The rat organ homogenates bound the antibiotic by 34--72 per cent.     

Antihypertensive profile of the angiotensin-converting enzyme inhibitors CI-906 and CI-907

CI-906 and CI-907, new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors, were examined for antihypertensive effects in unanesthetized hypertensive rats and dogs. In two-kidney, one-clip Goldblatt hypertensive rats, single oral daily doses (0.03-30 mg/kg) produced dose-dependent decreases in blood pressure; a single 3 mg/kg oral dose lowered blood pressure to normotensive levels. In spontaneously hypertensive rats, 30 mg/(kg X day) orally administered for 5 consecutive days achieved the same blood pressure decrease as that obtained on the first day in the renal hypertensive rats. In diuretic-pretreated renal hypertensive dogs, a 10 mg/kg oral dose decreased blood pressure by 25%. No adverse side effects were observed with CI-906 and CI-907 in any of the conscious animals. These studies indicate that CI-906 and CI-907 are potent, orally active antihypertensive agents without any apparent limiting side effects.     

Benzonidazole levels in blood vary with age in rats

Benznidazole (Bz) exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg). We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals.     

Bioavailability of peroral drug forms of oxacillin]

Bioavailability of experimental tablets and capsules of oxacillin was studied. Significant differences in absorption of the antibiotic from the above dosage forms were found. By the amount of the antibiotic absorbed the capsules were 3 times more effective than the tablets containing the same amount of oxacillin. The therapeutic concentrations of oxacillin in the blood after the use of the capsules persisted by an hour longer than after the use of the tablets. The results of the study on oxacillin absorption in rabbits allowed a prediction of the antibiotic absorption levels in humans.     

Erythromycin and oleandomycin concentration in the body of angina patients taking the preparations orally]

The antibiotic levels in patients suffering from angina were studied with the agar-diffusion method. The drugs were used orally in single and multiple doses (every 6 hours): erythromycin in doses of 4000 and 6000 gamma/kg and oleandomycin in doses of 4000 and 8000 gamma/kg. When erythromycin was used in a single dose of 4000 gamma/kg, its levels in the objects tested, i.e. the blood serum, saliva, mucus from the tonsil surface and tissue did not reach the concentrations corresponding to the sensitivity levels of the microbes to the antibiotic (0.75 gamma/ml). When the drug was used every 6 hours, the concentration increased. Still, it reached the above level only in the blood and tonsil surface mucus. Only when the antibiotic was used repeatedly in doses of 6000 gamma/kg, its levels in the examined objects reached 0.75 gamma/ml. When oleandomycin was used in single and repeated doses of 4000 gamma/kg, its levels were always lower than those providing sensitivity of beta-hemolytic streptococci to it (1.0 gamma/ml). The antibiotic use in doses of 8000 gamma/kg provided the required level in all the object examined.     

Comparative pharmacokinetics of erythromycin target cell-associated transport and intravenous administration in patients with pneumonia]

The method of cell-associated antibiotic therapy consists of extracorporal exposure of the autoblood formed elements to antibiotic solution followed by their reinfusion. Pharmacokinetics of erythromycin after its intravenous and cell-associated administration in patients with community-acquired pneumonia and the clinical efficacy of the method were evaluated. HPLC of the erythromycin pharmacokinetic pattern in 20 patients showed that after the antibiotic target transport the pharmacokinetic model changed from one-compartment to two-compartment one and the antibiotic maximum concentration and elimination rate were lower vs. the intravenous administration. It was also shown that the clinical efficacies of the erythromycin intravenous administration and target transport did not significantly differ, whereas after the cell-associated transport of the antibiotic the therapeutic effect was observed earlier and the side effects were less frequent.     

Hemodialysis Properties of Clindamycin (7-Chloro-7-Deoxylincomycin)

The effect of hemodialysis (Kolff-type machine) on clindamycin blood levels in anuric patients was studied. At 1 hr after oral ingestion of drug, blood levels ranged from 1.23 to 5.17 mug/ml and fell thereafter. Half-times for peripheral removal were 3.36 mug/ml +/- 0.22 when subjects were "off" dialysis and 3.14 mug/ml +/- 0.09 during dialysis. Their difference was not statistically significant, indicating that hemodialysis does not affect the blood level of clindamycin. In all studies, significant levels of the antibiotic were present at 12 hr.