The biodegradation of fenitrothion (an organophosphorus pesticide) in garden soil of western Uttar Pradesh in northern India has been studied. Both natural and autoclaved soil were treated with 10 p.p.m. of fenitrothion at field capacity moisture and incubated for 90 days in glass containers at 25 and 40 degrees C. The soil samples were collected at various intervals between 0 and 90 days and analysed by HPLC for the residual pesticide and metabolites formed. At 0 days the recovery of the pesticide was 98% and the pesticide then degraded linearly with incubation time. The concentration of pesticide in the natural soil decreased with incubation time with concomitant formation of two metabolites at 25 degrees C and three metabolites at 40 degrees C. These metabolites were purified to homogeneity by HPLC and characterized by IR spectroscopy. The results showed oxidative desulphuration of the pesticide at the first step followed by hydrolytic cleavage of P-O-aryl linkage and demethylation at the second and third step, respectively.

Biodegradation, Environmental↗

PubMedDate not supplied

Differential effects of organometallic tin compounds on Na+/K+-ATPase activity.

In vitro effects of six dibenzyltin dichloride (A-series) and another six dibenzyltin diisothiocyanate (B-series) complexes on Na+/K+-ATPase were studied. The rat brain synaptic membranes were prepared and significant ATPase inhibition was observed with all the complexes in a dose-dependent manner. The order of potency on Na+/K+-ATPase activity of the chloride complexes was found to be higher than that of the isothiocyanate complexes. The IC50 values range from 64 microM to 252 microM for the chloride complexes and from 132 microM to 399 microM for the isothiocyanate complexes. A structure-activity relationship could be derived for the chloride complexes.

Animals↗

PubMedDate not supplied

Metabolic fate of fenitrothion in liver, kidney and brain of rat.

The metabolic fate of fenitrothion, O,O-dimethyl-O-(3-methyl-4-nitro phenyl) phosphorothioate, was investigated in rat tissues during the first 24 hours following the intramuscular administration of the pesticide in the animal. High performance liquid chromatography (HPLC) of the pesticide and its metabolites formed in liver, kidney and brain showed the time-dependent sequential conversion of the pesticide into three major metabolites. These metabolites were separated and purified to homogeneity by HPLC and characterized by IR spectroscopy as O,O-dimethyl-O-)3-methyl-4-aminophenyl) phosphorothioate (metabolite I), O,O-dimethyl phosphorothioate (metabolite II), and O,O-dimethylphosphate (metabolite III). These results indicated reduction of the nitro group in fenitrothion aas the first step, followed by the hydrolytic cleavage of the P-O-aryl bond in metabolite I and the oxidative desulphurylation of metabolite II. Fenitrothion was found to induce ultrastructural changes in liver cells especially after 12 h exposure nuclear membrane was completely distorted, nuclear intactness was totally lost and smooth endoplasmic reticulum and Golgi apparatus were abnormally enlarged. In 24 h, however, the regeneration of the nuclear material was observed.

Animals↗

PubMedDate not supplied

Hepatic encephalopathy in cirrhotic and portacaval shunted dogs: lack of changes in brain GABA uptake, brain GABA levels, brain glutamic acid decarboxylase activity and brain postsynaptic GABA receptors.

It has been suggested, from studies of a rabbit model of fulminant hepatic failure, that hepatic encephalopathy might be related to an increase in brain gamma-aminobutyric acid uptake through a more permeable bloodbrain barrier, leading to an overactivity of brain gamma-aminobutyric acid-mediated inhibitory neurotransmission. Five groups of dogs were studied: normal dogs, dogs with secondary biliary cirrhosis without and with hepatic encephalopathy and portacaval shunted dogs without and with hepatic encephalopathy. Brain gamma-aminobutyric acid and sucrose uptake was investigated using the multiple indicator dilution curve technique in unanesthetized dogs. Tracer doses of 99mTc-labeled albumin (extracellular reference substance), 3H-labeled gamma-aminobutyric acid and 14C-labeled sucrose prepared in autologous dog plasma were injected in one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Uptake was calculated by comparing the areas under the 99mTc-labeled albumin and the [3H]gamma-aminobutyric acid (or [14C]sucrose) curves from appearance to peak height. After killing, brain gamma-aminobutyric acid levels were measured in the frontal cortex by high-performance liquid chromatography and glutamic acid decarboxylase activities using a radioenzymatic assay. Brain gamma-aminobutyric acid postsynaptic receptors were assessed using [3H]muscimol binding studies. There were no significant changes in cirrhotic and shunted dogs with or without hepatic encephalopathy with regard to brain gamma-aminobutyric acid and sucrose uptake, brain gamma-aminobutyric acid levels and glutamic acid decarboxylase activities. [3H]Muscimol binding studies did not show any changes in the number nor in the affinity of postsynaptic gamma-aminobutyric acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

The binding patterns of antisera to sex steroids and human gonadotropins on human and rhesus monkey spermatozoa.

The presence of different hormones on the surface of ejaculated spermatozoa was determined by immunofluorescence studies of the binding patterns of specific antisera to these hormones. There were striking similarities in the binding pattern of antisera to steroid hormones found on human and monkey spermatozoa. Assuming the intensity of fluorescence is proportional to the concentration of the hormone, concentrations of testosterone on the acrosomal and the postacrosomal regions were higher than levels of progesterone and estrogens. Spermatozoa with a "tapering head" had more hCG bound on the acrosomal and postacrosomal regions than spermatozoa with "normal head" (oval shaped). Correlating these findings to the functions of spermatozoa will require further studies.

Animals↗

PubMedDate not supplied

Discovery and design of novel inhibitors of botulinus neurotoxin A: targeted 'hinge' peptide libraries.

Intoxication by the zinc protease botulinus neurotoxin A (BoNT-A) results from cleavage of a single Q-R bond in the neuronal protein SNAP-25, which disables the docking mechanism required for neurotransmitter release. In the present study, potential inhibitors of BoNT-A were assessed from their effects on the BoNT-A cleavage of a synthetic 17-mer peptide (SNAP-25, residues 187-203) spanning the Q-R cleavage site. Compounds that inhibited BoNT-A included thiols (zinc chelators) such as dithiothreitol, dimercaptopropanesulfonic acid, mercaptosuccinic acid and captopril. In addition, compounds containing multiple acidic functions, such as the SNARE motif V2 (ELDDRADALQ), the tripeptide Glu-Glu-Glu and the steroid glycoside glycyrrhizic acid, were effective inhibitors. 'Hinge' peptide mini-libraries (PMLs) having the structure acetyl-X(1)-X(2)-linker-X(3)-X(4)-NH(2) or X(1)-X(2)-linker-X(3), where X(1)-X(4) were mixtures of selected amino acids and the flexible linker was 4-aminobutyric acid, also provided effective inhibition. Targeted PMLs containing the acidic amino acids Asp and Glu, the scissile-bond amino acids Gln and Arg and the zinc chelators His and Cys produced pronounced inhibition of BoNT-A. Deconvolution of these libraries will provide novel ligands with improved inhibitory potency as leads in the design of peptide mimetics to treat BoNT poisoning.

Antitoxins↗

PubMedDate not supplied

In vitro evaluation of a new temporary venous filter: the Spring filter.

PURPOSE: To evaluate in vitro the function efficacy of a new variable-sized, temporary venous filter, the Spring filter (SF). METHODS: The SF was tested in a flow phantom, using flexible, thin-walled polyethylene tubes 12, 14, and 16 mm in diameter to simulate veins. Clots of three sizes were used: 6 x 10 mm, 6 x 20 mm, 9 x 20 mm. Filter deployment was performed, ensuring that its functional diameter after placement was a predetermined multiple of the radius 'r' of the tube: 3.0r, 2.8r, 2.6r, 2.4r. The terminal coil was visually examined for changes in configuration. Clot retention by the filter for a period of 3 min was recorded as a success. The baseline intraluminal pressure and the maximum pressure reached after clot introduction were recorded. The trapping ability was calculated from the results for 10 clots. The effect of the following parameters on filter function were studied: size of embolus, caliber of simulated vein, and functional diameter of filter. RESULTS: The filter configuration was stable. Not a single instance of axial tilting occurred on deployment. Functional diameter was the major determinant of filter function. One hundred percent of clots were trapped irrespective of clot size and tube caliber when the functional diameter was 3.0r. Only 73% (95% confidence interval (CI): 57% - 88%) and 77% (95% CI: 61% - 92%) of small emboli were held up by the filter when the functional diameters were 2.6r and 2.4r, respectively (p = 0.0001). A significant reduction in clot trapping was encountered even with medium clots when the functional diameter was 2.4r (p = 0.02). CONCLUSION: Against the background of available data on retrievable vena caval filters, the current model of SF warrants further investigation.

Equipment Design↗