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PubMed1996

Benzyl-N-acetyl-alpha-D-galactosaminide inhibits the sialylation and the secretion of mucins by a mucin secreting HT-29 cell subpopulation.

We have analysed the mucins synthesized by the HT-29 MTX cell subpopulation, derived from the HT-29 human colon carcinoma cells through a selective pressure with methotrexate (Lesuffleur et al., 1990, Cancer Res 50: 6334-43), in the presence of benzyl-N-acetyl-alpha-galactosaminide (GalNAc alpha-O-benzyl), which is a potential competitive inhibitor of the beta 1,3-galactosyltransferase that synthesizes the T-antigen. The main observation was a 13-fold decrease in the sialic acid content of mucins after 24 h of exposure to 5 mM GalNAc alpha-O-benzyl. This effect was accompanied by an increased reactivity of these mucins to peanut lectin, testifying to the higher amount of T-antigen. The second observation was a decrease in the secretion of the mucins by GalNAc alpha-O-benzyl treated cells. The decrease in mucin sialylation was achieved through the in situ beta-galactosylation of GalNAc alpha-O-benzyl into Gal beta 1-3GalNAc alpha-O-benzyl, which acts as a competitive substrate of Gal beta 1-3GalNAc alpha 2,3-sialyltransferase, as shown by the intracellular accumulation of NeuAc alpha 2-3Gal beta 1-3GalNAc alpha-O-benzyl in treated cells.

Acetylgalactosamine↗
PubMed1991

Effect of bis(benzyl)polyamine derivatives on polyamine transport and survival of Brugia pahangi.

A potent filaricidal effect of bis(benzyl)polyamine derivatives is reported; the addition of 1 microM MDL 27695 to Brugia pahangi maintained in vitro killed the worms within 1 week. Using the labelled derivative, MDL 27391 uptake was demonstrated and evidence was provided for an uptake system that is independent of and clearly distinguishable from those for polyamines. The Km value for the uptake of MDL 27391 was determined to be 2 microM, and that for putrescine, spermidine, and spermine was 4.9, 1.7, and 4.8 microM, respectively. The uptake of MDL 27391 was not affected by polyamines. In contrast, bis(benzyl)polyamines were shown to be strong inhibitors of both the putrescine and the spermidine/spermine uptake system. As shown for MDL 27391, bis(benzyl)polyamines are not metabolized after uptake by Brugia worms; therefore, it is expected that the filaricidal effect of the drug depends on its interaction with potential polyamine-binding sites.

Animals↗
PubMed1989

Pharmacodynamics of benzyl chloride in rats.

In today's world of high industrialization, toxicity and pollution have become common terms of references. Both laymen and experts are becoming increasingly concerned about various health hazards created by occupational and industrial wastes dumped in and around public places. Benzyl chloride (BCl) was one of the chemicals dumped by Hooker Chemicals in Love Canal, N.Y. Benzyl chloride (BCl) is extensively used in industry in the manufacture of dyes, perfumes, resins, and synthetic tannins. It has been found at various dump sites and industrial wastes, which has led to potential hazards to health. This study was conducted to investigate the pharmacodynamics of BCl in rats. Rats were given 14C-BCl in corn oil by gavage. The peak plasma level was reached at 30 min and began to decline. BCl elimination pattern follows a two compartment model. The distribution half-life (alpha-phase) was 1.3 hr while the half-life of elimination (beta-phase) was 58.53 hr. Distribution studies after 48 hr of BCl administration revealed that the concentration of radioisotopes was highest in the stomach, gastric content, ileum, and duodenum followed by liver, adrenal, bone marrow, whole blood, pancreas, lung, esophagus, skin, kidney, heart, thymus, fat, testes, spleen, brain, and carcass. Approximately 76% of the initial dose was excreted by kidney during the 72 hr studies. About 7% was detected in expired air as 14CO2, while less than 1.3% was present as 14C-BCl or 14C-BCl metabolites in expired air during 72 hr. Metabolism studies revealed that S-benzyl-N-acetyl cysteine, benzyl alcohol, and benzaldehyde were the metabolites present in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Pancreatic exocrine secretion and immunoreactive secretin release after intraduodenal instillation of 1-phenyl-1-hydroxy-n-pentane and HCl in rats.

Portal plasma immunoreactive secretin (IRS) concentrations, pancreatic juice flow, and amylase output were simultaneously measured in response to intraduodenal infusion of 1-phenyl-1-hydroxy-n-pentane (PHP), as well as infusion of hydrochloric acid (HCl). These data were compared with those obtained from intravenous bolus injections of synthetic porcine secretin in anesthetized rats. The intraduodenal infusion of PHP or HCl at a rate of 2 ml/min for 2 min produced a dose-related increase in portal plasma secretin concentrations, pancreatic juice flow, and amylase output. However, the mechanism of secretin release by PHP seems to differ from that of HCl. The secretin response to 0.1 N HCl infused at a rate of 0.1 ml/min for 30 min was complete after 10 min, despite continued infusion, while PHP stimulated a secretin release which persisted for 10 min after cessation of infusion. The pH in the second portion of the duodenum, following PHP infusion, remained consistently greater than 6.3. PHP-stimulated pancreatic exocrine secretions were only partially suppressed by somatostatin, while secretin release was almost completely inhibited. However, intraduodenal PHP may stimulate the release of secretin along with other gastrointestinal hormones, and the endogenous release of these hormones may not be inhibited by somatostatin.

Amylases↗
PubMed1978

[The influence of tinofedrine on fibrinogen and platelet aggregation in patients with recent cerebral infarction (author's transl)].

The influence of Tinofedrine (0.12--0.17 mg/kg. bodyweight) on fibrinogen and platelet aggregation has been investigated in 45 patients (mean age 65 years) with recent cerebral infarction. Depending on the duration of medication a significant decrease of the fibrinogen level as well as of enhanced platelet aggregation has been observed. It is concluded from the present results that the decrease of enhanced platelet aggregation may be mediated by the fall of fibrinogen.

Aged↗
PubMed1975

The non-enzymic reduction of nitrite by benzyl viologen (free-radical) in the presence and absence of ammonium sulphate.

Some similarity is inferred between the reaction or reduced benzyl viologen with undissociated nitrous acid, which is significant at pH values below 7 and that with the undissociated product of nitrite ion and ammonium sulphate; presumably ammonium nitrite. This would explain why the presence of ammonium sulphate appreciably offsets the effects of decreasing pH and also the exponential relationship between rate of nitrite loss and ammonium sulphate concentration. There are other features of the reaction which cannot be explained at present, especially with regard to the degree of reduction of benzyl viologen. It is nevertheless apparent that a complex non-enzymic reaction yielding several products occurs when ammonium sulphate is present and that the presence of likely residual quantities after its use in enzyme purification may cause serious errors in enzyme assay.

Ammonium Sulfate↗