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PubMed1982

Nuclear mutations in Saccharomyces cerevisiae conferring multiple sensitivity to petite-inducing treatments.

Eighteen EMS-induced mutant strains of S. cerevisiae with increased sensitivity to petite induction by sulfanilamide-aminopterin treatment have been isolated. Four of these strains demonstrated a concomitant increase in sensitivity to the petite-inducing effects of u.v. irradiation and of growth at an elevated temperature. Of these, two were shown to be a consequence of recessive nuclear mutations at one gene (sas1-1 and sas1-2). Expression of the two remaining mutations was too low to permit genetic analysis. All three petite-inducing treatments used in this study are known to reduce the hydrogen bond strength between the two strands of double stranded DNA, and the existence of multiple sensitivity is discussed in terms of an alteration of a mitochondrial endonuclease which acts preferentially at sites of reduced attraction.

Aminopterin↗
PubMed1987

Membrane-associated carbonic anhydrase in gills of the blue crab, Callinectes sapidus.

The presence of the enzyme carbonic anhydrase (CA) on the basal membrane of the branchial endothelial cells in the blue crab and its physiological significance were studied in vivo using a membrane-impermeant CA inhibitor, quaternary ammonium sulfanilamide (QAS). Injection of QAS into the hemolymph of Callinectes sapidus resulted in the rapid development of a respiratory acidosis; PCO2 rose almost 2 Torr, pH was lowered by approximately 0.25 units, and total CO2 rose by 2 mM. These results support the hypothesis that membrane-associated CA exposed to hemolymph is present in the crustacean gill and that it is physiologically significant in mobilizing hemolymph HCO-3 to CO2 to facilitate CO2 excretion across the gill. The recovery from this acidosis coincides with the clearance of the inhibitor from the hemolymph. Hemolymph osmotic and ionic parameters were unaffected by QAS, reconfirming the role of branchial cytoplasmic CA in ion regulation and also providing a convenient bioassay for determining CA inhibitor permeability in the intact organism.

Acid-Base Equilibrium↗
PubMed1988

Thermodynamic study on enhancement of percutaneous penetration of drugs by Azone.

The mechanism whereby Azone (AZ, 1-dodecylazacycloheptan-2-one) enhances drug penetration through the hairless rat abdominal skin was investigated thermodynamically. Three kinds of drugs, indomethacin, ibuprofen and sulfanilamide which have similar solubilities in a mixed organic solvent (ethanol-diethylcarbitol, 40:60 v/v), were selected to evaluate the drug penetration with or without 5% AZ. Transdermal delivery rates were determined at 27 and 37 degrees C by using an in vitro diffusion cell procedure and the abdominal full-thickness skin of hairless rat. The solubility of each of the three drugs in the solvent with AZ was similar to that without AZ. Ethanol in the vehicle penetrated through the skin prior to the drugs. Activation energies for the skin penetration of the three drugs in the presence of AZ were decreased compared to those in its absence. For all drugs the partition coefficients between the skin and vehicle with AZ were 2-80 times higher than those without it. The activity coefficients of drugs in the presence of AZ in the skin were 2-90 times lower than those without the enhancer. These results suggested that the enhancing effect of AZ was not due to changing the solubility of the drugs in solvents but to increasing the thermodynamic activities and the affinities of the drugs to skin.

Administration, Cutaneous↗
PubMed1975

Effect of chlorinated hydrocarbons on shell gland carbonic anhydrase and egg shell thickness in Japanese quail.

Japanese quail (Coturnix japonica) were fed different levels of pesticide in their diets for 15 weeks. The levels of pesticide used were 25, 50, 100, 200 p.p.m. DDE 25, 50, 100, 200 p.p.m. DDT and 50 p.p.m. PCB. Carbonic anhydrase activities were analyzed in the shell glands and blood; pesticide concentration in the eggs of the first experiment was measured; egg weight, shell weight and shell thickness were also measured. No depression in growth was observed at any levels of pesticides used. Quail fed 200 p.p.m. DDE showed a high mortality rate after 10--12 weeks on the diet, while other levels produced no increase in death rate. Lower levels of DDT and DDE (25 and 50 p.p.m.) had no significant effect on egg shell weight or thickness. Higher levels (100 and 200 p.p.m) of DDT and DDE produced a small increase in shell weight and a 5 per cent decrease in shell thickness and were associated with increased shell breakage. At levels of 25 p.p.m. and 50 p.p.m. DDE, the activity of carbonic anhydrase in the shell gland was significantly increased. At levels of 200 p.p.m. DDE and 100 p.p.m. DDT in the diet, the activity of carbonic anhydrase was decreased by 12--15 per cent. A 50 per cent reduction in carbonic anhydrase activity in the shell gland seemed to be necessary for an increased production of soft shelled eggs when it was induces by sulfanilamide. Pesticide residues in the eggs of Japanes quail up to about 300 p.p.m. DDE and 150 p.p.m. DDT were not associated with any change in egg shell thickness. At about 600 p.p.m. DDE and 500 p.p.m. DDT in the eggs, corresponding to 100 and 200 p.p.m. in the diet, the egg shell thickness was reduced by 5 per cent. PCB at 50 p.p.m. produced a small decrease (4.5 per cent) in shell thickness and an increase in the percentage of cracked eggs.

Animals↗
PubMedDate not supplied

[The influence of different sugar reducing preparations on several pathogenetic components of diabetic angiopathy].

On the basis of clinico-laboratory examination of 500 patients suffering from diabetes mellitus a comparison was made of the influence of treatment with insulin and sulfanilamides on disturbed metabolic processes promoting development of vascular affections. There were found no differences in the action of insulin and oral agents on the indices of lipid, protein and mucopolysaccharide metabolism and on activity of the enzymes of the pentose-phosphate cycle. Corticosteroid excretion normalized with the compensation of diabetes, irrespective of the type of the sugar-reducing preparations. A more pronounced increase in catecholamine excretion was seen in insulin therapy apparently in connection with greater variations in glycemia level. A conclusion was drawn on analogous effect of insulin and sulphanilamides on the metabolic changes under study in diabetes. In difference from the action of insulin, a marked allergization of the of the organism accompanying the action of sulphanilamides, and their normalizing effect on the vascular permeability should be referred to the positive aspects of sulphanilamide action.

17-Hydroxycorticosteroids↗
PubMed1992

Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide.

Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule.

Adult↗
PubMed1991

[The drug sensitivity of meningococci and the characteristics of its determination].

The results obtained in the study of antibiotic and sulfamide sensitivity of 197 Neisseria meningitidis strains of groups A, B and C, isolated from the spinal fluid and blood of patients with meningococcal infection hospitalized in the 2nd Clinico-Infectious Hospital, Moscow, in 1984-1989 and studied with the use of the disc diffusion method and the method of serial dilutions of antibiotics in solid culture media, are presented. As revealed in this study, N. meningitidis strains retained their high sensitivity to penicillin and ampicillin (MIC50 = 0.016 and 0.032 micrograms/ml respectively). Sensitivity to tetracycline decreased (MIC50 = 0.5 micrograms/ml) and to rifampicin increased (MIC50 = 0.063 micrograms/ml). 48.5% of strains were resistant to streptomycin. In recent years the proportion of N. meningitidis, resistant to sulfanilamide preparations, significantly decreased and MIC50 was equal to 2.5 micrograms/ml in comparison with 5-10 micrograms/ml in the preceding period. The results of testing sensitivity to antibiotics by both methods coincided. Still the disc diffusion method can be used in epidemiological surveillance on meningococcal infection, while for more exact differentiation of N. meningitidis strains the use of the method of serial dilutions is necessary.

Anti-Bacterial Agents↗
PubMed1989

[Antibiotic resistance in clinical strains of Pseudomonas aeruginosa isolated from 1979-1984].

The levels and spectra of drug resistance were determined in 530 strains of P. aeruginosa isolated in hospitals of three cities of the USSR within 1979-1984. Their conjugative R plasmids were searched for and distribution of various type resistance determinants in the composition of these plasmids was investigated. The results were compared with the findings of analogous studies on clinical strains of P. aeruginosa isolated within 1976-1979. It was shown that there were a rise in the relative number of the strains resistant to kanamycin and a decrease in the occurrence of the P. aeruginosa strains resistant to streptomycin, tetracycline and sulfanilamides. The frequency of the kanamycin, carbenicillin and gentamicin resistance genes in the composition of the detected conjugative R plasmids increased. Hybridization of 32P-labeled probes containing various type antibiotic resistance determinants with strains of P. aeruginosa ML (PAO) containing conjugative R plasmids was indicative of wide spread of genes determining APH(3')II and APH(3") and determinants of classes A and C in the composition of the studied plasmids.

Carbenicillin↗
PubMed1977

[Drug resistance of phage types of Salmonella typhimurium (author's transl)].

Antimicrobial susceptibility testing (disk diffusion test) and phage typing (method according to Anderson, performed by Prof. Brandis, Bonn) of 703 strains of Salmonella typhimurium from humans, isolated in Essen and surrounding during 1972 to 1975, was performed to dertermine whether characteristic patterns of drug resistance were associated with a single phage type or not. The most frequently isolated phage types are phage type 17 (12.2%), 12 (10.1%), 49 (8.1%), 15a (5.7%), 2 (3,3%) and the untypable phage type (46.7%). Resistance to tetracycline (45%) was most common, followed by resistance to sulfanilamide (19%), ampicillin (9%), and chloramphenicol (7%). Resistance to other antimicrobial agents (trimethoprim/sulfamethoxazol, gentamicin, colistin) was quite rare. Antibiograms of different phage types were found to be different, not only as far as the ratio of sensitive to resistant strains is concerned, but also for the ratio single-resistant to multiple-resistant strains. These differences were found to be statistically significant (chi-square-test, table 2). Comparison of antimicrobial resistance to tetracycline showed, that the portion of resistant strains was about 70% for the untypable phage types, 40% for phage type 17 and 7% for phage type 12. Among isolates of the phage type 49 multiple resistance was most common. The combination of resistance determinants is specified in figure 3. A possible interrelation between resistance pattern and the presence of R-plasmids in isolated strains is discussed.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Human pharmacokinetic characteristics of sulfamonomethoxine depending on the drug form].

Comparative study of sulfamonomethoxin pharmacokinetics in the man given the drug per os or parenterally in the form of methylglucaminate showed that the latter favours higher blood concentrations of the drug 12 hours following injection. Sulfamonomethoxinmeglumin is absorbed more rapidly and has a greater bioavailability. The drug is mainly excreted with urine, more than a half being excreted in an acetylated form. It is recommended that the initial and maintenance doses be not less than 1000 and 500 mg for both dosage forms respectively. The interval between sulfanilamide administrations should not exceed 24 hours.

Adult↗
PubMedDate not supplied

Spontaneous formation of immunogenic conjugates by 5-aminosalicylic acid--a biotransformation product of salicylazosulfapyridine.

5-Aminosalicylic acid (5-ASA) reacts readily with proteins at alkaline pH and forms conjugates capable to induce hapten specific antibodies in rabbits. Extensive immunological cross reactions have been found between 5-ASA and para-aminophenol (PAP) immunological systems, but no cross reactions were found between 5-ASA and orto-aminophenol (OAP) immunological systems. Moderate cross reactions were found, occasionally between 5-ASA, 3-hydroxy-sulfanilamide (3-HS) and alpha-methyldopa (alpha MD) immunological systems. Antibodies directed against normal rabbit serum (NRS) proteins, which served as carrier in the 5-ASA conjugates used for immunization, were found in the sera of three out of the six rabbits inoculated with such conjugates. Antibodies directed against heterologous proteins were found in all of these sera, including one serum which lacked hapten specific antibodies and the three sera lacking antibodies directed against NRS proteins. The significance of these findings for the interpretation of the immuno-allergic reactions induced by sulfasalazine is discussed.

Aminosalicylic Acids↗
PubMed1984

Nitrosation by alkyl nitrites. Catalysis by inorganic salts.

Isobutyl nitrite is an effective nitrosating agent at acidic, neutral and basic pH in the presence of species arising from phosphate ion. The reaction is first-order in isobutyl nitrite and amine. In the reaction of isobutyl nitrite with sulfanilamide, the pH dependence reflects the change in concentration of the various protonated forms of phosphate, with H3PO4 and H2PO4- most strongly affecting the rate. In the reaction of isobutyl nitrite with dipropylamine, the pH dependence also reflects the change in the concentration of unprotonated amine.

Catalysis↗
PubMed1983

[Treatment of staphylococcal pneumonias].

Sensitivity of 129 strains of pathogenic staphylococci isolated from patients with pneumonia was studied with respect to a large number of drugs in the Bacteriological Laboratory of Konstantiny in the Algerian People's Democratic Republic. The method of paper discs and the Müller-Hinton solid nutrient medium were used. The staphylococcal strains were highly sensitive to cephalosporins, some of aminoglycosides (neomycin, gentamicin, tobramycin), nitrofurans, rifampicin, some antibiotics of other groups. Minocycline proved to be the most active among the tetracycline antibiotics. The number of the strains sensitive to it amounted to 82 per cent. 74--76 per cent of the isolates were resistant to tetracycline and oxytetracycline. 40--77 per cent of the isolates were resistant to sulfanilamides.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Several indices of the functional state of the adrenals of white rats during a prescribed course of sulfadimezine and sulfamonomethoxine combined with UV-irradiation].

Chronic treatment with sulfadimesin or sulfamonomethoxin combined with UV irradiation leads to potentiation of adrenocortical function. As the observation period increases, the weight ratios of the adrenals grow which is accompanied by the decreased content of ascorbic acid in them and by the reduced weight ratios of the goiter and spleen. Combined chronic use of sulfanilamides and UV irradiation results in an increase of the total acetylating capacity of the body, especially in the day time.

Acetylation↗