Effectiveness of the intramuscular administration of high doses of penicillin in treating pneumonia]

Clinical tolerance of benzylpenicillin administered intramuscularly in doses of 2000000--3000000 units every 4--6hours (12000000 units a day) was studied in 253 patients with pneumonia. Satisfactory tolerance of sodium benzylpenicillin and pronounced painfulness at the site of injection of potassium benzylpenicillin were noted. General toxic side effects in the form of asthenia, dizziness, pain in the heart region were observed in a part of elderly patients. The benzylpenicillin serum levels after administration of 2000000 units were 6--10 times higher than those after administration of 200000 units. The efficiency of benzylpenicillin elevated doses was studied in 193 patients. In 101 of them the previous treatment with usual doses of benzylpenicillin, i. e. 200000 units every 4 hours was not sufficiently effective. The elevated doses of benzylpenicillin proved to be effective in 78 per cent of the cases, the effect being observed in all the cases with acute pneumonia, in 88.5 per cent of the cases with neglected state and in 83 per cent of the cases with chronic pneumonia. The therapeutic effect was also observed in most of the patients with benzylpenicillin resistant microflora in the sputum. On the basis of high efficiency of penicillin therapy it was concluded that gram-positive cocci played the main role in pneumonia etiology.     

Comparative characteristics of the antibioticograms and biological properties of the staphylococci isolated from patients with various eye diseases]

A total of 1488 examinations of the conjunctival content of patients with various ophthalmic diseases were performed within 5 years (1973--1977). 989 (66.4 per cent) cultures were isolated. Staphylococci were isolated in 79.2 per cent of the patients irrespective of the diagnosis. The plasma-coagulating strains were isolated in 43.6 per cent of the patients with acute conjunctivitis. The plasma-negative staphylococci were more frequent in chronic conjunctivitis (83.5 per cent). A total of 188 strains were studied according to 18 tests. Determination of the antibiotic sensitivity showed that the number of the benzylpenicillin and tetracycline resistant strains among the plasma-coagulating staphylococci was higher in the patients with acute ophthalmic diseases. In chronic conjunctivitis no differences in the antibiotic sensitivity of the plasma-coagulating and plasma-negative strains were noted. Similar antibiotic sensitivity of all plasma-negative staphylococci irrespective of the diagnosis was found. High biological activity of the plasma-negative staphylococci was shown: 74.1 per cent of the isolates possessed phosphatase, 59.8 per cent possessed protease and 88.4 per cent a lysozyme-like enzyme. The strains isolated in chronic conjunctivitis produced protease more frequently that those isolated in acute ophthalmic diseases.     

Action of penicillin on the erythrocyte membrane

The effect of the therapeutic concentrations of benzylpenicillin on potassium release and osmotic resistance of the red blood cells in healthy children was investigated potentiometrically with the use of a K+-selective electrode. In a concentration of 0.66 mM (370 units/ml) benzylpenicillin increased the total content of potassium in the cells and their resistance to osmotic lysis and lowered the rate of K+ release induced by valinomycin. The membrane stabilizing effect of benzylpenicillin observed in these studies could to some extent stipulate its nonspecific antiinflammatory effect. In a concentration of 1.32 mM (740 units/ml) it had no significant effect on the indices studied. Under the effect of the maximum concentrations of the antibiotic (3.3 mM) the signs of lowered stability of the red blood cell membranes were observed, i.e. an increased rate of the valinomycin induced release of K+ and a tendency for the decreasing of the osmotic resistance.     

Neutrophil-mediated methemoglobin formation in the erythrocyte. The role of superoxide and hydrogen peroxide

Human neutrophils incubated with phorbol myristate acetate oxidized hemoglobin within the intact erythrocyte by a mechanism dependent on cell-cell contact but independent of phagocytosis. Spectrophotometric examination of the erythrocyte lysates revealed that the major component formed was methemoglobin along with small amounts of a species with spectral characteristics similar to choleglobin. Methemoglobin formation was directly related to the neutrophil concentration and the time of incubation. The addition of superoxide dismutase or catalase modestly inhibited the formation of methemoglobin, while a combination of the enzymes provided the most dramatic protection. Methemoglobin of hydroxyl radical or hypochlorous acid scavengers. Apparently, either O2.- or H2O2 alone was capable of mediating methemoglobin formation in the intact erythrocyte. Maintenance of the intraerythrocytic hemoglobin in its oxygenated state or its derivatization to carbon monoxyhemoglobin markedly inhibited methemoglobin formation. Blockade of the anion channels in the intact erythrocyte with sulfonated stilbenes inhibited O2.- but not H2O2 from oxidizing intracellular hemoglobin. It appears that neutrophil-derived O2.- and H2O2 can cross the erythrocyte membrane through the anion channel or diffuse directly into the intracellular space and react with oxyhemoglobin or deoxyhemoglobin to form a mixture of hemoglobin oxidation products within the intact cell.     

E. coli resistance to antibiotics on the material studied and the structure of the antibiotic resistance of the strains]

Standard filter paper discs were used to determine the sensitivity of 943 strains of E. coli isolated in 1970-1974 from patients' purulent-inflammatory foci with respect to benzylpenicillin, streptomycin, levomycetin, tetracycline, erythromycin and monomycin. An increase in the specific weight of the cultures resistant to the 6 drugs from 4.7 +/- 1.7 per cent in 1970 to 16.0 +/- 2.6 per cent in 1974 was observed. Strains resistant to 5--6 antibiotis were more often isolated from the urine (64.6 per cent) and the wound content (48.9 per cent) and rarer from the abdominal cavity exudate (23.1 per cent), bile (28.0 per cent) and sputum (30.1 per cent). Most often certain combinations of resistance to benzylpenicillin, streptomycin, tetracycline and erythromycin were found in the E. coli strains tested.     

A comparative evaluation of the pharmacokinetics of different forms of benzathine benzylpenicillin]

Comparative randomized opened pharmacokinetic evaluation of benzathine benzylpenicillin in three dosage forms was performed. Benzathine benzylpenicillin was used as extencilline (2.4 million U or 1.2 million U, "Rh?ne-Poulenc Rorer", France) and as bicillin-5 (1.5 million U, "Synthesis" Russia). 33 patients were included in investigation (23 women and 10 men aged 16-60 years). 25 persons had verified rheumatism without blood circulation failure signs, 4--had chronic tonsillitis and 4 were healthy volunteers. Benzylpenicillin concentration was estimated by microbiology test in blood samples taken at 1, 3, 24 hours and 7, 14 and 21 days after intramuscular drug injection. After 2.4 million U extencilline injection (12 patients) its concentration, was at the inhibition level for beta-hemolytic streptococcus group A (25 ng/ml) for 3 weeks-period in 83.3 per cent of patients. After 1.2 million U extencilline injection (10 patients) or 1.5 million U bicillin-5 injection (12 patients) the above mentioned concentration was achieved on the 21st day in 30 and 0 per cent of patients respectively. Thus the treatment with benzathine benzylpenicillin at the 1.2 million U dose in the form of extencilline or bicillin-5 doesn't provide adequate antistreptococcal concentration in blood in prolonged period and is not suitable for correct rheumatism prophylaxis in adult patients.     

The role of superoxide in the destruction of erythrocyte targets by human neutrophils

Human neutrophils exposed to the soluble stimulus, phorbol myristate acetate, generate a flux of O2.- which can destroy human erythrocyte targets. Under optimal conditions, each neutrophil was capable of lysing almost 10 erythrocyte targets. Hemolysis was inhibited by exogenous copper-zinc or iron superoxide dismutase while neither heat-denatured enzyme nor albumin inhibited cytotoxicity. Although neutrophils can also generate H2O2, neither catalase nor a glutathione-glutathione peroxidase system inhibited hemolysis. Hemolysis was prevented by conversion of the hemoglobin to carbon monoxyhemoglobin, suggesting an intracellular mechanism of cytotoxicity. Conversion of hemoglobin to methemoglobin by nitrite treatment did not impair neutrophil-mediated hemolysis. However, nitrite-treated targets were not protected by superoxide dismutase, while exogenous catalase inhibited cytotoxicity, suggesting a potential role for H2O2 and methemoglobin. H2O2 and methemoglobin are known to interact to form an oxidant complex whose cytotoxic potential was underlined by the marked sensitivity of nitrite-treated cells to commercial H2O2. It is proposed that neutrophil-derived O2.- oxidizes oxyhemoglobin to generate methemoglobin and H2O2 which interact to form a cytotoxic complex capable of hemolyzing the erythrocyte target.     

Effect of sulfalene and furosemide on benzylpenicillin kinetics in rats with aseptic inflammation

The effect of sulfalen and furosemide on benzylpenicillin kinetics in blood serum, intact tissues and aseptic inflammation foci was studied on rats. It was shown that under the action of sulfalen and furosemide protein binding of benzylpenicillin lowered by 30 per cent. The changes in the antibiotic kinetics after combined use with sulfalen and furosemide were of the same type: markedly increased concentrations in blood serum and tissues and retarded elimination.     

The effect of antioxidants on in vivo and in vitro methemoglobin formation in erythrocytes of patients with Parkinson’s disease

Methemoglobin formation was examined in erythrocytes of 16 patients with Parkinson’s disease (PD) (stage 3–4 by the Hoehn and Yahr scale). The patients receiving levodopa-containing drugs (madopar, nakom) were also treated with intramuscular injections of mexidol (daily dose 100 mg/day) for 14 days. Control group included 12 clinically healthy persons. The erythrocyte methemoglobin content was determined by electronic paramagnetic resonance (EPR) using the EPR signal intensity with the g-factor 6.0. The methemoglobin content was significantly higher in erythrocytes of PD patients than in healthy donors. The complex therapy with mexidol normalized the methemoglobin content in erythrocytes of PD patients. Incubation in vitro of erythrocytes of donors and PD patients with acrolein increased the methemoglobin content, while incubation with carnosine normalized the methemoglobin content in erythrocytes of PD patients. Prophylactic (i.e. before acrolein addition) and therapeutic administration of carnosine to the incubation system with acrolein decreased the methemoglobin content to its initial level. Results of this study suggest that inclusion of the antioxidants mexidol and carnosine in the scheme of basic therapy of PD may reduce side effects associated with methemoglobinemia.     

Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication]

The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).     

Effect of the functional state of the internal organs on the pharmacokinetics of benzylpenicillin in angina]

The levels of benzylpenicillin on its intramuscular administration in doses of 100000 or 200000 units, as well as the renal and hepatic functions and the antibiotic binding by the host protein components were studied in 44 angina patients and 29 healthy persons. The benzylpenicillin levels were always markedly higher in the angina cases than those in the healthy persons. The ratio of the free and protein bound fractions of the antibiotic in the above groups was practically the same. At the same time the amount of benzylpenicillin excreted with the urine was higher in the angina patients than in the healthy persons approximately by 2 times. The study of the function of the internal organs revealed a marked decrease in the daily diuresis in all the angina patients and microhematuria in the 1/4 of the cases. The impairment of the renal function was determined by the laboratory methods practically in all the patients. On the basis of the data obtained it was concluded that the increased benzylpenicillin levels in the angina cases were connected with a decreased capacity for inactivating this substance by the liver enzymatic systems due to the changed function of this organ. The fact of the increased antibiotics levels in the host is considered as a positive phenomenon providing inhibition of the disease causative agents resistant to usual concentrations of the drug.     

Investigations on the antioxidative defence responses to NaCl stress in a mangrove, Bruguiera parviflora: Differential regulations of isoforms of some antioxidative enzymes

Two-month-old healthy seedlings of a true mangrove, Bruguiera parviflora, raised from propagules in normal nursery conditions were subjected to varying concentrations of NaCl for 45 d under hydroponic culture conditions to investigate the defence potentials of antioxidative enzymes against NaCl stress imposed oxidative stress. Changes in the activities of the antioxidative enzymes catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (POX), glutathione reductase (GR) and superoxide dismutase (SOD) were assayed in leaves to monitor the temporal regulation. Among the oxidative stress triggered chemicals, the level of H₂O₂ was significantly increased while total ascorbate and total glutathione content decreased. The ratio of reduced to oxidized glutathiones, however, increased due to decreased levels of oxidized glutathione in the leaf tissue. Among the five antioxidative enzymes monitored, the APX, POX, GR and SOD specific activities were significantly enhanced at high concentration (400 mM NaCl), while the catalase activities declined, suggesting both up and downregulations of antioxidative enzymes occurred due to NaCl imposed osmotic and ionic stress. Analysis of the stress induced alterations in the isoforms of CAT, APX, POX, GR and SOD revealed differential regulations of the isoforms of these enzymes. In B. parviflora one isoform of each of Mn-SOD and Cu/Zn-SOD while three isoforms of Fe-SOD were observed by activity staining gel. Of these, only Mn-SOD and Fe-SOD2 content was preferentially elevated by NaCl treatment, whereas isoforms of Cu/Zn-SOD, Fe-SOD1 and Fe-SOD3 remained unchanged. Similarly, out of the six isoforms of POX, the POX-1,-2,-3 and -6 were enhanced due to salt stress but the levels of POX-4 and -5 remained same as in control plants suggesting preferential upregulation of selective POX isoforms. Activity staining gel revealed only one prominent band of APX and this band increased with increased salt concentration. Similarly, two isoforms of GR (GR1 and GR2) were visualized on activity staining gel and both these isoforms increased upon salt stress. In this mangrove four CAT-isoforms were identified, among which the prominent CAT-2 isoform level was maximally reduced again suggesting differential downregulation of CAT isoforms by NaCl stress. The results presented in this communication are the first report on the resolutions of isoforms APX, POX and GR out of five antioxidative enzymes studied in the leaf tissue of a true mangrove. The differential changes in the levels of the isoforms due to NaCl stress may be useful as markers for recognizing salt tolerance in mangroves. Further, detailed analysis of the isoforms of these antioxidative enzymes is required for using the various isoforms as salt stress markers. Our results indicate that the overproduction of H₂O₂ by NaCl treatment functions as a signal of salt stress and causes upregulation of APX, POX, GR and deactivations of CAT in B. parviflora. The concentrations of malondialdehyde, a product of lipid peroxidation and lipoxygenase activity remained unchanged in leaves treated with different concentrations of NaCl, which again suggests that the elevated levels of the antioxidant enzymes protect the plants against the activated oxygen species thus avoiding lipid peroxidation during salt stress.     

Antibiotics in the treatment of wounds in the victims of the earthquake in the Armenian SSR

Purulent wounds in 88 victims of the Armenian earthquake with the syndrome of long-term squeezing were examined microbiologically and the experience with using antimicrobial drugs for their treatment was analyzed. In all the cases microbial associations were detected, coliform and nonfermenting gram-negative bacilli, enterococci, anaerobes and yeast-like fungi being isolated from 80, 20, 15 and 25 per cent of the patients respectively. 130 bacterial strains were studied in detail. 80 to 100 per cent of the bacterial isolates were resistant to the antibiotics routinely used in surgical practice, i.e. benzylpenicillin, tetracycline, levomycetin, kanamycin, cephalothin and cefazolin and highly sensitive to new antimicrobial drugs belonging to ureidopenicillins (mezlocillin), quinolones (ciprofloxacin) and cephalosporins of the 3rd generation (cefoperazone and ceftazidime). Retrospective estimation of the antibiotic therapy revealed its inadequacy in 55.7 per cent of the patients for the most part because of the isolates resistance. The 19 variants of the antibiotic use prescribed by the physicians mainly included penicillins, aminoglycosides and their combinations (in 67.2 per cent of the cases). The use of the highly efficient drugs of the groups of ureidopenicillins and quinolones was extremely rare which was likely due to lacking of information on the drugs.     

Effect of electrophoresis of the head region on benzylpenicillin penetration across the blood-brain barrier

A procedure for administration of sodium benzylpenicillin (SB) to the brain was developed and tested on 22 rabbits. SB was administered drop-like intravenously in a dose of 200,000 units/kg body weight in combination with electrophoresis of the head area. It was shown spectrophotometrically that a single administration of SB increased its concentration in the liquor and brain tissues by 366.7 and 500 per cent respectively as compared to the control values. Practically no shifts in the EEG and ECG were observed which was indicative of safety of SB administration by that route. The procedure for intraorgan administration of SB in combination with electrophoresis may be recommended for clinical use.     

Peroxide metabolism enzymes in diabetic children: relationship to duration and control of diabetes

Enzyme activities of erythrocyte superoxide dismutase (SOD), peroxidase and catalase in groups of diabetic children, the duration of the disease and control qualities were compared with respective values obtained for healthy children. Generally the disease duration was clearly found to affect SOD activity, and catalase activity only a little. No similar influence of either diabetes duration or control was noticed in the case of peroxidase. SOD activity was diminished in diabetics when compared with control subjects, and in turn peroxidase and catalase activities were generally elevated. The diminution in SOD activity may constitute a reason for enhanced pancreatic cells susceptibility to deterioration, followed by the augmentation of peroxidase activity with an 'elaborated' mechanism compensating for the loss of erythrocyte SOD activity.     

Effects of beta-carotene,vitamin C and E on antioxidant status in hyperlipidemic smokers

Smoking can accelerate the consumption of the stored antioxidant vitamins and increase the oxidative stress in the hyperlipidemic patients. The study investigated the effects of combined beta-carotene, vitamin C, and vitamin E on plasma antioxidant levels, erythrocyte antioxidative enzyme activities, and LDL lipid peroxides. Male hyperlipidemic smokers (35-78 years old) were randomly divided into two antioxidant supplemented groups: intervention 1 (I1, n = 22) (15 mg beta-carotene/day, 500 mg vitamin C/day, and 400 mg alpha-tocopherol equivalent/day) and intervention 2 (I2, n = 20) (30 mg beta-carotene/day, 1000 mg vitamin C/day, and 800 mg alpha-tocopherol equivalent/day). After 6-week supplementation, plasma beta-carotene, vitamin C, vitamin E, and erythrocyte glutathione levels increased significantly by 200%, 98%, 129%, and 39%, respectively, in the I1 group, and by 209%, 216%, 197%, and 32%, respectively, in the I2 group. Plasma Fe(+2) concentrations and Fe(+2)/Fe(+3) decreased significantly in both groups. Except erythrocyte glutathione peroxidase activity in the I1 group, erythrocyte catalase, glutathione peroxidase, and superoxide dismutase activities increased significantly in both groups. Lipid peroxides in LDL decreased significantly by 56% and 72% in the I1 and I2 groups, respectively. However, the levels of plasma iron, erythrocyte glutathione, and LDL lipid peroxides, and the activities of erythrocyte antioxidative enzymes did not differ between two groups. In conclusion, combined antioxidant supplements increased plasma antioxidant levels and antioxidative enzyme activities, and lowered LDL lipid peroxides in male hyperlipidemic smokers. Higher dosage of the supplements did not have an additive effect.     

Effect of various carbon and nitrogen sources on the biosynthesis of ristomycin, protease and pigments by a culture of Nocardia fructiferi var. ristomycini

The effect of various sources of carbon and nitrogen on the biosynthesis of ristomycin, protease and pigments by Nocardia fructiferi was studied. It was shown that the carbon sources had the most significant effect on the biosynthesis of the antibiotic. The maximum biosynthetic activity of the Nocardia was observed in the medium containing 1-2 per cent of soybean meal and 2 per cent of glycerol. Under such conditions all the three biologically active substances formed. The contents of ristomycin, protease and pigments amounted to 562-649 microgram/ml, 26-30 PU/ml and 0.45-0.63 conditional units, respectively.     

The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes

The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals. The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.     

Acute lindane intoxication: A study on lindane tissue concentration and oxidative stress-related parameters in liver and erythrocytes

Treatment of rats with daily dosis of 20 mg of lindane/kg for 3 consecutive days led to the accumulation of the insecticide in several tissues, including erythrocytes and liver. Lindane did not alter the hematocrit and hemoglobin concentration but reduced methemogiobin levels by 17%. Red blood cells from controls and lindane-treated rats, exposed to t-butyl hydroperoxide, exhibited comparable rates of oxygen uptake and visible chemiluminescence, whereas the induction period that precedes oxygen uptake was significantly enhanced in the latter group. Lindane treatment did not modify the activity of erythrocyte glutathione peroxidase, glucose-6-phosphate dehydrogenase, catalase, and methemoglobin reductase, being the total content of glutathione and superoxide dismutase activity significantly increased. The liver from lindane-treated rats showed an enhanced microsomal pro-oxidant activity, evidenced by higher cytochrome P450 content and NADPH-cytochrome c reductase and NADPH oxidase activities. The higher enzyme activities led to an increased superoxide anion generation (adrenochrome formation) and lipid peroxidation (measured either by the production of thiobarbituric acid reactants and spontaneous visible chemiluminescence). Concomitantly, liver glutathione content and the activity of glutathione peroxidase-glutathione reductase couple were augmented by lindane treatment, without any change in superoxide dismutase activity, together with a reduction in that of catalase. Results suggest that lindane does not alter the prooxidant/antioxidant status of the erythrocyte in conditions of a significant cellular accumulation of the insecticide, which might exert direct action on enzymatic systems leading to enhanced superoxide dismutase activity and glutathione content. In the liver, lindane-induced pro-oxidant condition was not accompanied by cell injury, probably due to the adaptative increase in some antioxidant mechanisms of the hepatocyte.     

Selenium – an antioxidative protectant in soybean during senescence

Selenium (Se) is regarded as an antioxidant in animals and plants, even though considered as non-essential element in plants. To test its ability to counteract senescence related oxidative stress in soybean a pot culture experiment was conducted. The soybean plant was sprayed with sodium selenate (50ppm) at 78days after sowing (DAS). Soybean leaves were harvested at 80 and 90 DAS for analysis of oxidant production and antioxidative enzymes activity. Se positively promoted growth and acted as antioxidant by inhibiting lipid peroxidation and per cent injury of cell membrane. The antioxidative effect was associated with an increase in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes activity. Significant increase in antioxidant enzyme activity was positively related to Se content. The decrease in antioxidative enzymes at 90 DAS was much faster in control plants than Se-sprayed plants. The reduction in SOD and GSH-Px may be associated with senescence-induced oxidative burst.