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Metabolism of Sorbitol in the intact organism.

1) Uniformly labeled sorbitol and DD-fructose, respectively, are compared int he rat after intragastral administration in regard to their incorporation patterns into respiratory CO2, fatty acids and glycerol of adipose tissue triacyglycerols, liver cholesterol and glycogen. The results demonstrate clearly that fructose cannot be considered as the sole or main intermediate of the metabolic degradation of orally administered sorbitol in the intact organism. 2) When sulfanilamide undergoes acetylation in the rat after intragastral application of U-14C-labeled precursors, acetylsulfanilamide isolated from the urine possesses a much higher specific radioactivity after sorbitol than after fructose administration. 3) Human volunteers of both sexes exhale considerable quantities of hydrogen (H2) through their lungs, after oral sorbital administration but only small amounts after fructose administration. 4) The results prove that sorbital had been absorbed only partially in the small intestine, and undergoes fermentation in lower parts of the digestive tract (caecum in rats, colon in men) which leads, amongst other products. to acetate. Products of microbial metabolization are absorbed and utilized by the host organism. Different isotope incorporation patterns, varying specific radioactivities in acetylsulfanilamide, and H2 formationi men are thus explained. Therefore the degradation of orally administered sorbitol does not proceed in the intact organism, to a remarkable extent as is the case with fructose or other monosaccharides; pecularities of the effects of dietary sorbitol become understandable.

Adipose Tissue↗

[Presence of nitrogen compounds in well water].

INTRODUCTION: Nitrogen compounds in drinking waters have been related to groundwater contamination and inadequate sanitary conditions. Nitrite and nitrate are etiologic agents of methemoglobinemia. In acid solution, nitrous acid formed from nitrite can react with secondary amines to form carcinogenic nitrosamines. The survey of ammoniacal and albuminoid nitrogen, nitrite and nitrate in groundwater supplies as regards the extent of the contamination they cause and discussion of the drinking water regulation regarding nitrogen compounds. MATERIAL AND METHOD: Samples collected predominantly in the Metropolitan Region of S. Paulo City was analysed for nitrogen compounds using colorimetric methods: N-NH3 and N-albuminoid by the Nessler method, nitrite by diazoted sulfanilamide with N-(1-naphthyl)-ethylenediamine, and nitrate by reaction with phenoldisuplhonic acid. RESULTS: Federal and S. Paulo State drinking water regulations, respectively, Portaria 36/90 and Decreto n degree 12.486, were applied to interpret the results obtained. Of the 607 samples analysed. 15% of them had at least one of the concentrations of nitrogen compounds exceeding the maximum contaminant level (MCL) of the S. Paulo State Regulation. Otherwise, as regards the Federal Regulation, only 4% of the samples exceeded the MCL requirement for nitrate. CONCLUSION: In federal drinking water regulation only MCL for nitrate is reported. Otherwise, S. Paulo State regulation requirements report MCLs for all the compounds that have been analysed in this work. The observed results showed that concentrations of ammonia and albuminoid nitrogen, and nitrite, as well as nitrate, gave rise to water of inadequate quality, further they may have adverse effects on human health. The inclusion of nitrogen compounds other than nitrate in federal regulation is recommended.

Ammonia↗

Effects of anion and cation inhibitors and carbonic anhydrase inhibitors upon the activity of the gypsy moth (Lepidoptera: Lymantriidae) nucleo-polyhedrovirus.

Twenty chemicals that were reported to act as anion transport inhibitors, cation transport inhibitors, and inhibitors of carbonic anhydrase activity were tested at a 1% concentration (wt:wt) for their effects upon the biological activity of the gypsy moth, Lymantria dispar (L.), nucleopolyhedrovirus (LdMNPV). Among the five anion transport inhibitors tested, flufenamic acid acted as a viral enhancer. None of the seven inhibitors of K+ enhanced viral activity and three (4-aminopyridine, diacetyl, and procaine) significantly reduced the activity of LdMNPV. All four Na+ transport inhibitors (abietic acid, amiloride, dicyclohexylcarbodiimide, triamterene) acted as viral enhancers. Triamterene was the most active enhancer, as the LC50 was reduced by approximately 1,750-fold. Five carbonic anhydrase inhibitors were tested and four (acetazolamide, hydrochlorothiazide, methazolamide, sulfanilamide) enhanced the activity of LdMNPV. Acetazolamide (a carbonic anhydrase inhibitor), amiloride (a Na+ transport inhibitor), and flufenamic acid (an anion transport inhibitor) were tested singly and in different combinations. Every combination tested (acetazolamide/amiloride, acetazolamide/flufenamic acid, amiloride/flufenamic acid, acetazolamide/amiloride/flufenamic acid) significantly decreased the LC50 from 7.79 PIB/mm2 to a value as low as 0.008 PIB/mm2 (amiloride/flufenamic acid).

Acetazolamide↗

Sorption of sulfonamide pharmaceutical antibiotics on whole soils and particle-size fractions.

Residues of pharmaceutical antibiotics are found in the environment, whose fate and effects are governed by sorption. Thus, the extent and mechanisms of the soil sorption of p-aminobenzoic acid and five sulfonamide antibiotics (sulfanilamide, sulfadimidine, sulfadiazine, sulfadimethoxine, and sulfapyridine) were investigated using topsoils of fertilized and unfertilized Chernozem and their organic-mineral particle-size fractions. Freundlich adsorption coefficients (K(f)) ranged from 0.5 to 6.5. Adsorption increased with aromaticity and electronegativity of functional groups attached to the sulfonyl-phenylamine core. Adsorption to soil and particle-size fractions increased in the sequence: coarse silt < whole soil < medium silt < sand < clay < fine silt and was influenced by pH. Sorption nonlinearity (1/n </= 0.76) indicated specific interactions with functional groups of soil organic matter (SOM). Phenolic and carboxylic groups, N-heterocyclic compounds, and lignin decomposition products were tentatively assigned as preferred binding sites using statistical analysis of pyrolysis-mass spectra and adsorption coefficients. Adsorption of sulfonamides to mineral soil colloids was weaker and resulted in a stronger desorption from clay-size fractions. Moreover, steric accessibility of organic-mineral complexes in clay-size fractions was significantly reduced. With a quantitative structure-property relationship (QSPR) model, combining the organic carbon concentration, the sulfonamides' chromatographic capacity factor (k'), and nondissociated species concentration (CF(a)), distribution coefficients (K(d)) were estimated with a cross-validated regression coefficient Q(2) = 0.71. Modeling and molecular mechanics calculations of antibiotic-SOM complexes showed preferred site-specific sorption via hydrogen bonds and van der Waals interactions. Distinct chemical structural properties, such as aromaticity and van der Waals volumes, correlated with the sorption data.

Adsorption↗

[Titration method for determination of carcinine (beta-alanyl-histamine). Application to the heart of Carcinus maenas (L.)].

1.--Carcinine was isolated by ion-exchange chromatography and titrated spectrophotometrically. The technique used was based on formation of an azo derivative of carcinine with sulfanilamide at basic pH. It allowed detection of carcinine at 1 microgram/ml concentration. 2.--Histamine could be detected simultaneously with the same technique, provided its concentration was greater than 1 microgram/ml. 3.--The mean amount of carcinine in cardiac tissues of Carcinus maenas was 22.1 micrograms/ml dry cardiac tissue. 4.--The technique described above did not allow detection of histamine in the heart of Carcinus maenas. If present, histamine must be at a concentration smaller than 0.1 microgram/ml dry cardiac tissue.

Animals↗

Carbonic anhydrase inhibitors: synthesis of Schiff bases of hydroxybenzaldehydes with aromatic sulfonamides and their reactions with arylsulfonyl isocyanates.

Reaction of o- or p-hydroxybenzaldehydes with sulfanilamide, homosulfanilamide and p-(2-aminoethyl)- benzene-sulfonamide afforded several new Schiff bases which were subsequently derivatized at the phenolic hydroxy moiety by reaction with arylsulfonylisocyanates. The new arylsulfonylcarbamates obtained in this way possessed interesting inhibitory properties against three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human, b = bovine isozyme). All these new derivatives, the simple Schiff bases and the arylsulfonylcarbamates obtained as outlined above, were more inhibitory against all isozymes as compared to the corresponding parent sulfonamide from which they were obtained. Generally, the p-hydroxybenzaldehyde derivatives were more active than the corresponding ortho isomers. An interesting behavior was evidenced for some of the ortho-substituted arylsulfonylcarbamato-sulfonamides, which showed higher affinities for the isozyme hCA I, as compared to hCA II and bCA IV (generally hCA I is 10-1000 less sensitive to "normal" sulfonamide inhibitors, such as acetazolamide, methazolamide or dorzolamide, as compared to hCA II). This make the new derivatives attractive leads for designing isozyme I-specific inhibitors.

Animals↗

Carbonic anhydrase inhibitors: aromatic sulfonamides and disulfonamides act as efficient tumor growth inhibitors.

Aromatic/heterocyclic sulfonamides generally act as strong inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). Here we report the unexpected finding that potent aromatic sulfonamide inhibitors of CA, possessing inhibition constants in the range of 10(-8)-10(-9) M (against all the isozymes), also act as efficient in vitro tumor cell growth inhibitors, with GI50 (molarity of inhibitor producing a 50% inhibition of tumor cell growth) values of 10 nM-35 microM against several leukemia, non-small cell lung cancer, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer cell lines. The investigated compounds were sulfanilyl-sulfanilamide-, 4-thioureido-benzenesulfonamide- and benzene-1,3-disulfonamide-derivatives. The mechanism of antitumor action with these sulfonamides is unknown, but it might involve either inhibition of several CA isozymes (such as CA IX, CA XII, CA XIV) predominantly present in tumor cells, a reduced provision of bicarbonate for the nucleotide synthesis (mediated by carbamoyl phosphate synthetase II), the acidification of the intracellular milieu as a consequence of CA inhibition or uncoupling of mitochondria and potent CA V inhibition among others. A combination of several such mechanisms is also plausible. Optimization of such derivatives from the SAR point of view, might lead to the development of effective novel types of anticancer agents/therapies.

Antineoplastic Agents↗

Carbonic anhydrase inhibitors. Schiff bases of some aromatic sulfonamides and their metal complexes: towards more selective inhibitors of carbonic anhydrase isozyme IV.

Reaction of three aromatic sulfonamides possessing a primary amino group, i.e., sulfanilamide, homosulfanilamide and p-aminoethyl-benzenesulfonamide with heterocyclic and aromatic aldehydes afforded a series of Schiff bases. Metal complexes of some of these Schiff bases with divalent transition ions such as Zn(II), Cu(II), Co(II) and Ni(II) have also been obtained. The new compounds were assayed as inhibitors of three isozymes of carbonic anhydrase (CA). Several of the new compounds showed a modest selectivity for the membrane-bound (bovine) isozyme CA IV (bCA IV) as compared to the cytosolic human isozymes hCA I and II, in contrast to classical inhibitors which generally possess a 17-33 times lower affinity for bCA IV. This greater selectivity toward bCA IV is due mainly to a slightly decreased potency against hCA II relative to classical inhibitors. However, metal complexes of these Schiff bases possessed an increased affinity for hCA II, being less inhibitory against bCA IV. The first type of compounds reported here (i.e., the Schiff bases of aromatic sulfonamides with heterocyclic aldehydes) might thus lead to the development of low molecular weight isozyme specific CA IV inhibitors. The difference in affinity for the three isozymes of the inhibitors reported by us here is tentatively explained on the basis of recent X-ray crystallographic studies of these isozymes and their adducts with substrates/inhibitors.

Aldehydes↗

[Wound myiasis caused by Lucilia sericata].

Report of a case of miyasis in Lucilia sericata infected wounds recently observed in Paris in a 67-year-old vagrant. The authors describe the role played by Lucilia sericata in therapy before the appearance of sulfanilamides and antibiotics.

Aged↗

[Pseudomonas aeruginosa plasmids that control streptomycin resistance].

Wide distribution of streptomycin resistance determinants (83 per cent) among the resistance plasmids of the clinical strains of Ps. aeruginosa isolated in several clinics of 2 towns was found. Nine plasmids determining resistance to this antibiotic, as well as some other antibiotics, sulfanilamides, metallic ions, hydroxyanions and UV radiation were studied. The frequency of the conjugation transfer in these plasmids was different, i.e. from 10(1) to 10(6). They belonged to the following incompatibility groups: P-1, P-2, P-5 and apparently P-3. Eight out of the 9 plasmids determined the synthesis of streptomycin phosphotransferase which was evident of wide distribution of the streptomycin inactivation mechanism by phosphorylation among the strains of Ps. aeruginosa. The strains carrying the plasmids significantly differed by the content of the enzyme. However, all the enzymes could inactivate only streptomycin and dihydrostreptomycin and had approximately the same molecular weight (about 20 000). The strain carrying plasmid pBSII had no enzyme inactivating streptomycin (by phosphorylation or adenylation). The antibiotic resistance determined by this plasmid must be connected with changes in permeability of the bacterial cell wall by streptomycin.

Cell-Free System↗

[Clinico-immunologic effect of immunomodulin and bactim in duodenal ulcer under environmental pollution conditions].

There was a study of the effect of immunomodulin and bactrim (biseptol-480) preparations in 53 patients with duodenal ulcer living in the ecologically polluted Southern Aral region. It was revealed that the application of immunomodulator immunomodulin and bactrim, a combined sulfanilamide preparation, in combination with the conventional anti-ulcer treatment promotes stronger bactericidal activity with respect to Helicobacter pylori, development of the immune status of the organism, acceleration of ulcer cicatrisation, reduction of the average period of staying in an in-patient hospital, which is an indication of its economic efficiency.

Adjuvants, Immunologic↗

[The efficacy of the conservative treatment of patients with acute appendicitis on board ships at sea].

Under study was efficiency of conservative treatment of 247 patients with acute appendicitis on ships in the sea depending on the age of patients, clinical manifestations of the disease, volume of medicamentous therapy and time of taking medical advice. It was established that conservative treatment is most effective if started within the first 6 hs from the beginning of the disease and antibiotics were used in combination with spasmolytics, antihistamines and sulfanilamides. Patients treated conservatively had pronounced inclinations to delimiting the inflammatory process in the abdominal cavity.

Acute Disease↗

[Effect of antibiotics on the absorption of basic nutrients].

The impact of tetracycline, gentamicin, streptomycin, erythromycin, oxacillin, benzylpenicillin and sulfanilamides on the absorption function of the small intestine was studied in 79 patients with chronic bronchitis. The drugs were shown to mainly inhibit fat absorption: on the average, by 87 per cent in all the patients treated with tetracycline, on the average, by 89 and 36 per cent in 80-70 per cent of the patients treated with gentamicin and streptomycin, respectively, and, on the average by 26 and 16 per cent in 20-25 per cent of the patients treated with erythromycin and oxacillin, respectively. The absorption of protein decreased, on the average, by 23-74 per cent in all the patients treated with tetracycline, gentamicin and streptomycin. As for the other drugs, they had, on the average no significant effect on protein absorption. The absorption of carbohydrates (d-xylose) significantly decreased under the effect of these three drugs (by 21, 34 and 36 per cent, respectively). The analysis revealed a relation of absorption function to the presence and degree of intestinal dysbacteriosis.

Adult↗

[Antimicrobial activities of organic zinc compounds].

Taking into account the competitive action of zinc towards other ion essential for pathogenic germs metabolism, the complex erythromycin-zinc, zinc salts of sulfamethoxydiazine, sulfanilamide, sulfacetimide, sulfathiazole as well as the Mannich basis of sulfamethoxydiazine were synthetized. The antimicrobial action towards gram-positive, gram-negative pathogens and fungi was tested by the classic diffusiometric method. An increased antimicrobial action for the Mannich basis of sulfamethoxydiazine and for the zinc salt of sulfamethoxydiazine, alone or in association with metronidazole--chemotherapeutic agent used in the infections with anaerobic organisms was found. A significant antimicrobial action was also found for the complex erythromycin-zinc and zinc salts of sulfacetimide and sulfathiazole.

Anti-Bacterial Agents↗

Biochemical approach to new medications.

In this plenary symposium address, the author describes historically his progress from the antimetabolite 2,6-diaminopurine to 6-mercaptopurine as a useful drug against tumours and leukaemia. Subsequently a 6-mercaptopurine derivative, and eventually azathioprine, were discovered to be useful drugs to ensure kidney transplant acceptance. Several of his group's diaminopurines proved to be selective antifolates in combatting pathogenic bacteria when combined with sulfanilamide, a useful drug combination already estimated to have saved a million lives.

Antimetabolites↗

METHODS OF LABORATORY DIAGNOSIS OF GONORRHOEA USED IN THE USSR.

In this review of gonorrhoea diagnostic methods in current use in the USSR, the author stresses first the value of the examination of smears for the detection of the typical forms of the gonococcus. Where atypical L-forms are present, as may occur after treatment with antibiotics or sulfanilamide, microscopy may be misleading and a combination of laboratory methods is called for, including the use of culture techniques. Transport media for the maintenance of material for culture have been little used in the USSR so far, but experiments with the Stuart medium and modifications of it have shown promise.Although the complement-fixation test has lately fallen rather into disuse for gonorrhoea diagnosis, the author considers the inherent value of this serological method to warrant its further use provided that new and improved antigens and techniques can be developed capable of yielding specific reactions with both typical and atypical forms of the gonococcus.

Complement Fixation Tests↗

[The characteristics of treating odontogenic osteomyelitis against a background of malaria in the population of the Republic of Burundi].

All the patients were administered preoperative antimalarial therapy, antibiotics and sulfanilamides, and agents maintaining the defense factors, as well as detoxifying and desensitizing therapy. Rational nutrition was prescribed. All these measures helped liquidate the inflammation foci not only in the bones, but in the soft tissues of the paramaxillary area as well.

Adolescent↗