Effect of proteolytic enzymes on antibiotic distribution when the preparations are administered by different routes]

The effect of proteolytic enzymes, such as terrilitine and chymotripsin on pharmacokinetics of morphocycline and streptomycin in rats after their administration by various routes was studied comparatively. The oral use of the enzymes or their introduction directly into the duodenum simultaneously or 30 minutes before the antibiotic administration did not increase the morphocycline and streptomycin levels in the biosubstrates tested. A tendency to a decrease in the serum and organ levels of the antibiotics in animals when used orally in combination with the enzymes was noted. When the drugs were administered intramuscularly, the morphocycline serum and organ levels in the rats increased insignificantly, while the streptomycin levels increased significantly. Administration of formalin as a stressor had an analogous effect which provided a supposition of a possibility of non-specific effect of the enzymes of distribution of the antibiotics on intramuscular injection of the enzymes in large doses having a local irritating effect.     

Intracellular distribution of tetracyclines in rat hepatocytes

Distribution of tetracyclines, such as oxytetracycline, morphocycline, tetracycline, doxicycline and methacycline in the liver cells of rats was studied. The ratio of the subcellular structures, i. e. nuclei, mitochondria and microsomes and the liquid phase containing the drugs in the dissolved state in the system studied was close to the natural ratio of the hepatocyte organoids and cytoplasm. Distribution of tetracyclines in the subcellular fractions was not uniform. The nuclei did not absorb the drugs. The role of microsomes in drug absorption was insignificant. The mitochondria bound the highest amounts of the drugs and defined the characteristics of their intracellular distribution. The amounts of the drugs in the active form remaining in the cytoplasm after their contact with organoids were low. At the same time there was observed a a definite activating effect of the cytoplasm components on the antibiotics contained in it.     

Olemorphocycline treatment of calculous and noncalculous pyelonephritis]

40 patients suffering from calculous and non-calculous pyelonephrits were treated with olemorphocycline administered intravenously in a dose of 250 00 Units 2 times a day for 5--7 days. The clinical effect was observed in 62.5 per cent of the cases. In 54.7 per cent of the cases the isolates were resistant to oleandomycin and morphocycline. The kidney tissue and urine from the kidney pelvis taken during surgical operations of 20 patients were plated out. Staphylocci were most often detected in the platings of the kidney tissue. The microflora of the urinary bladder before the treatment and that of the urine from the kidney pelvis and the kidney tissue taken during the surgical operation was mainly ident     

Comparative study of the biological activity of tetracycline hydrochloride and morphocycline by using reverse turbidimetry]

The method of back turbidimetry was used for determination of the biological activity of the antibiotics, since high turbidity of the nutrient medium with Staph. aureus as the testculture prevented from direct measurements. Broth containing phosphate buffer, Staph. aureus and definite concentrations of the antibiotic was used as the reference solution. The experiments showed that the differences in the biological activities of tetracycline hydrochloride and morphocycline may be found with the method of back turbidimetry 6-8 hours after the microbe cultivation on media with the antibiotics.     

Effect of the physiological activity of Clostridium cells on their sensitivity to antibiotics]

Actively multiplicating cells of C1. perfringens proved to be more sensitive to 7-chlor-7-desoxylincomycin and rifampicin than the cells in the phase of the population dying. The bactericidal effect of the antibiotics on Clostridia vegetating at a temperature range within 37--4degrees was studied. Determination of the content of higher fatty acids in the cultivation medium with the method of gas chromatography showed that the metabolic processes in the bacterial cells went on at a temperature of 4degrees. Sensitivity of Clostridia to antibiotics at 20 and 4degrees lowered. However, all antibiotics inhibited the cell viability under such conditions. The inhibitors of the intracellular protein synthesis, i. e. rifampicin, 7-chlor-7-desoxylincomycin and morphocycline proved to be most active. The effect of beta-lactame antibiotics, i. e. cephaloridine and benzylpenicillin was reliable though lower.     

Antibiotic resistance of Pseudomonas aeruginosa strains isolated from patients with infected burns

Sensitivity to 15 drugs of 248 P. aeruginosa strains isolated from patients with infected burns was studied by the method of agar dilution. All of the strains were resistant to polymyxin M, ceporin, erythromycin and oleandomycin. Most of the strains were resistant to streptomycin, monomycin, ampicillin and rifadin. Moderate resistance of the strains to carbenicillin, morphocycline, vibramycin, kanamycin, tetraolean and tetracycline was observed: the maximum concentrations of these antibiotics (128 microgram/ml) inhibited the growth of 85, 69, 63, 51.8, 43.6 and 41.2 per cent of the strains respectively. Gentamicin proved to be most active against the strains of P. aeruginosa and inhibited 87 per cent of the strains when used in the therapeutic doses. The study provided recomendation of the drugs for parenteral and local use in treatment of burns infected with P. aeruginosa.     

Interaction of morphocycline with beryllium ions]

Behaviour of morphocycline (H5R) and its complex with beryllium ions in acqueous solutions was studied fluorimetrically. The ionization constants of H5R were estimated at pH 1.5-15 according to the data of fluorimetric determination with respect to OH-group: pK1 6.40, pK2 8.25, pK3 10.65, pK4 11.30. Two constants characterizing the deprotonization process with respect to the carbonylic group and nitrogen were also estimated: pK01--1.0 (greater than C = 0) and pK02 4.75 (--N=). Formation of an intensively fluorescing compound less than [Be3(OH)3(H2O2)5]2HR greater than 2+ was observed at pH 6.0-7.0. The cause of such intensive fluorescence was deformation of ion [Be3(OH)3(H2O)6]3+ because of its exclusion from the coordinating sphere of one molecule of water during the complex formation and decreasing of level H comes from II as compared to the morphocycline level II comes from n. A procedure for detecting morphocycline in the blood of humans and animals was developed.     

Results of using morphocycline for the treatment of fresh, uncomplicated gonorrhea in men]

A total of 30 males suffering from fresh non-complicated gonorrhea were treated with morphocycline (N-morpholinmethyltetracycline). The diagnosis in all cases was confirmed by bacterioscopic and cultural tests. The drug was administered intravenously in a dose of 0.15 mg 2 times at an interval of 12 hours. Stable recovery was observed in 17 patients. Resistance to the treatment was found in 4 patients and relapses of the disease within 1 to 9 days after the treatment discontinuation were registered in 9 patients. It was concluded that morphocycline in the usual doses was not sufficiently effective.     

土壤温度和湿度对长白松林土壤呼吸速率的影响

2003年6月17日、8月日和10月10日,研究了长白山长白松林地内土壤呼吸速率和断根土壤呼吸速率日变化,并于2004年5～9月对其季节变化进行了测定.结果表明,土壤总呼吸速率和断根土壤呼吸速率的日变化均呈单峰型,峰值一般出现在12:00～14:00,8月份土壤呼吸速率的日变化幅度小于6月份和10月份.土壤总呼吸速率、断根土壤呼吸速率和根系呼吸速率具有明显的季节变化,6～8月份较高,5月份和9月份较低.2004年5～9月份,土壤总呼吸速率、断根土壤呼吸速率和根系呼吸速率的平均值分别为3.12、1.94和1.18 μmolCO₂·m^-2·s^-1,根系呼吸对土壤总呼吸的贡献为26.5%～52.6%.土壤呼吸速率与土壤温度之间呈显著的指数相关,与土壤湿度之间呈线性相关.土壤总呼吸速率、断根土壤呼吸速率和根系呼吸速率的Q10值分别为2.44、2.55和2.27,断根土壤呼吸速率对温度的敏感程度大于土壤总呼吸速率和根系呼吸速率.土壤总呼吸速率对土壤湿度的敏感程度大于根系呼吸,断根土壤呼吸速率对土壤湿度的敏感程度最差.     

The effect of certain antibiotics on reproduction of the black bean aphid, Aphis fabae Scop.

The antibiotic terramycin at 0.2% concentration was consistently effective in greatly reducing the populations of Aphis fabae on Vicia faba when sprayed on larvae on and off the plant. The insects were not killed, but their fertility was decreased by over 97% in the first generation, leading to total sterility in the second generation. At 0.01% concentration, terramycin was not effective and only moderately so at 0.1% Larval development was invariably delayed by 1 day and the weight and size of the resulting adults were significantly reduced. After the most effective treatments, the adults were very inactive in their feeding and excretion, and sometimes became completely sterile. Even when the aphids reproduced, they ceased to do so after 6–10 days in different terramycin treatments and frequently the larvae were born dead. The affected insects could not, apparently, regain their reproductive capacity even after their transfer to untreated plants. When the insects were sprayed on the plants, terramycin in water was as effective as with surfactants: but when the insects were sprayed off the plants an oxyethyl phenol derivative (NP 10) greatly increased the efficiency of terramycin: surfactants alone had no effect on the insects. The other four antibiotics, namely tetracycline, aureomycin, chloramphenicol and reverin were not effective at the 0.2% concentration when the plants alone were sprayed before introducing the apids. The addition of glycerin to the antibiotics and keeping plants in a high humidity for 24 hr. after the treatment also had no effect.     

Myeloinhibitory effect of the action of some antitumor antibiotics and its comparative assessment]

General toxic and myeloinhibitory effects of some antitumor antibiotics, such as rubomycin, olivomycin, bruneomycin and karminomycin administered intraperitoneally in a single LD50 to mice were studied. It was found that the general toxicity of bruneomycin and karminomycin was almost the same and 5 to 8 times higher than that of rubomycin and olivomycin. The use of the above antibiotics resulted in definite shifts in the blood systems of healthy mice. The most significant suppression of hemopoesis accompanied by a pronounced depression of the number of the myelocariocytes was observed after the use of olivomycin. The effect of karminomycin was characterized by suppression of erythro-, myelo- and lymphopoesis and depression of the number of the granulocytes and lymphocytes of the blood. Bruneomycin and rubomycin had a short-time myeloinhibitory effect. The erythroid cords of the bone marrow proved to be most sensitive to the inhibitory effect of the antibiotics. However, inhibition of the erythropoesis accompanied by deep reticulocytopenia did not induce the respective depression of the erythrocyte number. The lymphoid cords was in the 2nd place by its sensitivity to the antibiotics and the myeloid and megocariocytal cords were in the 3rd and the 4th places respectively. Complete reduction of hemopoesis in the animals was observed by the 10th day of the drugs use.     

Acute and chronic hypoxia in rats. II. Effect on oxidative phosphorylation and in vitro protein synthesis in liver mitochondria and its subpopulations.

The objective of this investigation was to examine liver mitochondrial functions in rats exposed to 0.4 atm for 0, 5 and 27 days, Liver homogenates were fractionated by rate-zonal centrifugation utilizing iso-osmotic Ficoll-sucrose gradients; this eliminates loss of large and small mitochondria and makes possible the separation of mitochondria into subpopulations according to sedimentation coefficient. After pooling all mitochondrial fractions for obtaining composite determinations of the entire population, large diminutions in states 3 and 4 respiration (succinate as substrate) were obtained in day-5 and day-27 rats but no changes were evident with regard to ADP:O ratios, respiratory control indices or the capacity for in vitro protein synthesis. By examination of subpopulations of mitochondria, it was found that mitochondria are heterogeneous with regard to ADP:O ratios, respiratory control indices, states 3 and 4 respiration and the capacity for in vitro protein synthesis. The heterogeneity for each of these parameters was altered in day-5 and day-27 animals. Although states 3 and 4 respiration were depressed throughout the entire mitochondrial population for day-5 and day-27 rats, a subpopulation of mitochondria from day-27 rats showed respiratory control indices and ADP:O ratios which were higher than any subpopulation of mitochondria of either day-5 or day-0 animals.     

DIE WIRKUNG VERSCHIEDENER, ÜBER DIE PFLANZE ZUGEFÜHRTER ANTIBIOTICA AUF ENTWICKLUNG UND FERTILITÄT DER SCHWARZEN BOHNENBLATTLAUS APHIS FABAE

Zusammenfassung Unter dem Einfluss verschiedener Antibiotica wird die Larvalentwicklung von Bohnenblattläusen stark gehemmt. Diese Substanzen bedingen ausserdem geringere Größe und vermindertes Gewicht der Aphiden im Vergleich zu unbehandelten Kontrolltieren. Je nach Art und Konzentration des verwendeten Antibioticums bleiben die Aphiden entweder völlig steril oder ihre Reproduktionsfähigkeit wird unterschiedlich stark herabgesetzt. Bereits eine einbis zweitägige Terramycinaufnahme durch Aphiden während des ersten Larvenstadiums ist ausreichend, um beim adulten Tier völlige Sterilität hervorzurufen.

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Summary A considerable delay in larval development of black bean aphids was observed when they were kept permanently on Vicia faba plants in solutions containing antibiotics. The reduction in the weight and size of the aphids on treated plants were also marked in comparison with those on untreated plants. Furthermore, total sterility was observed in certain cases and reduced reproductive rate in others. This effect was related to the chemical constitution, and the concentration of the antibiotics tested. The most effective substances were: terramycin, aureomycin, tetracyclin, chloramphenicol, and reverin. All other antibiotics had none or only a slight impact on reproduction. Even when young larvae fed for a short period (one or two days) on terramycin treated plants, total sterility resulted. The relation between the larval development and reproductive rate of aphids, and the destruction of their symbiotes by antibiotics is discussed.

     

The effect of DMCM and diazepam on the behavior of rats subjected to ethanol exposure in the prenatal period]

White rats were given 4 g/lag daily of 40% ethyl alcohol from the 5th till the 20th day of pregnancy. Males of the off-spring from the 5th till 19th day were subjected to treatment with 0.6 mg/kg DMCM (4-ethyl-6, 7-dimethoxy-beta-carboline-3-carboxylate methyl ether) or 2.5 mg/kg of diazepam daily. It has been shown that both drugs normalize increased locomotor activity; treatment with DMCM corrects passive avoidance conditioned reflex retention; both drugs restore active avoidance conditioned reflex elaboration in rats alcoholized prenatally. Moreover, treatment with DMCM or diazepam restores correlations between behaviour indices and binding of 3H-diazepam which have been altered by prenatal alcoholization.     

Rifampicin effectiveness in experimental anaerobic gas infection]

The inhibitory effect of rifampicin against most of 82 strains of pathogenic Clostridia was evident at a concentration of less than 0.1 gamma/ml. The bactericidal concentrations were close to the bacteriostatic ones with respect to 74 strains. The protective effect of rifampicin in mice with experimental anaerobic gaseous infaction caused by different species of pathogenic Clostridia was evident at doses of 0.5 mg/kg. In infections caused by associations of Clostridia and Staph. aureus resistant to other antibiotics, rifampicin was effective, while ampicillin had no protective effect. Rifampicin administered 24 to 96 hours before the infection prevented the specific process. A number of other antibiotics, such as ampicillin, cephaloridin, morphocycline and 7-chlor-7-desoxylincomycin had no such a capacity. The prolonged prophylactic effect of rifampicin was associated with maintenance of low antibiotic levels in the blood and muscle tissues which were higher than the minimum inhibitory concentrations. The effect of rifampicin against the background of a rapidly developing process was less pronounced and limited in time.     

Anaerobic shift of energy metabolism in the mouse brain during the recovery period in acute radiation sickness

Three months after whole-body irradiation of mice with a sublethal dose of 5 Gy a study was made of some indices of energy metabolism like tissue respiration, oxidative phosphorylation, and formation of lactic acid in the survived brain homogenate. Revealed were the diminution of coupling of tissue respiration of oxidative phosphorylation, the rate of oxygen consumption and the level of cyano-resistant respiration being constant, the increase in the rate of glycolysis in anaerobic and particularly, in aerobic conditions, and reduction of the Pasteur and Crabtree effects. The above mentioned changes in the brain energy metabolism seem to be a manifestation of the process of the reduced metabolism formation in the nervous tissue at the remote times after irradiation.     

Changes in the matching of somato-autonomic rhythms in the human operator during learning]

In subjects during the 1st through 15th day of training of the assemble job, before and during the work, the changes of concordance between the heart rate and respiration rhythm were studied in comparison with the dynamics of the activity results and of psychophysiological characteristics. In subjects with bad results of learning higher indices of respiratory-cardiac concordance and tremor were initially observed, what may serve as a criterion for professional selection for this kind of activity. In well learning subjects during transition from rest to work the initial desynchronization of somato-vegetative rhythms ("stress" type of reaction) was changed by an increase of their concordance. The relation of the training success to the type of working capacity of the subject ("morning", "evening") was also revealed.     

Effect of rubomycin (daunorubicin) and its nitroxyl analog on the functioning of rat heart mitochondria

Changes in the functional parameters of the rat heart mitochondria were studied in time after a single intraperitoneal administration of rubomycin, the rubomycin combination with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO-OH) and ruboxyl, a nitroxyl derivative of rubomycin. The administration of rubomycin resulted in inhibition of the heart mitochondria bioenergetic functions (a decrease in the respiration control coefficient, RCC, and the respiration rate, RR, on phosphorylation) during respiration in the presence of NAD(+)-dependent substrates 6 to 24 hours after the administration. Later the mitochondria functions recovered while in 2 to 3 weeks a secondary decrease in the RCC and RR was observed. During respiration in the presence of succinate the inhibitory effect on the antibiotics was higher. The combined administration of rubomycin and TEMPO-OH eliminated the primary inhibition. In the presence of ruboxyl the inhibitory effect in regard to the NAD(+)-dependent substrates was not detected. The mechanisms of the toxic action of the anthracycline antibiotics are discussed.     

The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) have reduced bone mineral density (BMD). Although pHPT causes high bone turnover, the exact metabolic bone markers useful for predicting changes in BMD after parathyroidectomy (PTX) remain elusive. The present study was performed to examine the relationship between bone metabolic indices and BMD changes after PTX in 29 pHPT Japanese patients, which received PTX successfully. BMD values were measured by dual-energy X-ray absorptiometry in the lumbar spine and distal one third of radius. As for bone metabolic indices, serum bone-type alkaline phosphates (BAP), serum osteocalcin (OCN), urinary deoxypiridinoline (Dpd), and urinary type I collagen cross-linked N-telopeptides (NTX) were measured. The study included 10 male and 19 female patients (17 postmenopausal). Urinary Dpd, but not NTX was significantly correlated with serum BAP and OCN. Either bone formation or bone resorption indices were significantly and highly correlated with Z-score of BMD in the radius, but not at lumbar spine. Urinary Dpd was significantly correlated with BMD changes at both lumbar spine and radius and at all time points over the two years after PTX. These correlations were most potent among bone metabolic indices in this study. The measurement of urinary Dpd would be useful for predicting long-term changes in BMD at radial and lumbar spine after PTX than other bone metabolic indices.     

The action of certain antibiotics on mitochondrial, erythrocyte and artificial phospholipid membranes. The role of induced proton permeability

1. The action of the antibiotics enniatin A, valinomycin, the actin homologues, gramicidin, nigericin and dianemycin on mitochondria, erythrocytes and smectic mesophases of lecithin–dicetyl hydrogen phosphate was studied. 2. These antibiotics induced permeability to alkali-metal cations on all three membrane systems. 3. The ion specificity on each membrane system was the same. 4. Enniatin A, valinomycin and the actins did not induce permeability to protons, whereas nigericin and dianemycin rendered all three membrane systems freely permeable to protons. 5. Several differences were noted between permeability induced by nigericin and that induced by gramicidin. 6. The action of all these antibiotics on mitochondrial respiration could be accounted for by changes in passive ion permeability of the mitochondrial membrane similar to those induced in erythrocytes and phospholipid membranes, if it is assumed that a membrane potential is present in respiring mitochondria.