Biomedical subjects

T Motyl

Publications and source records attributed to T Motyl.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Application of sulforaphane: histopathological study of intraportal transplanted pancreatic islets into livers of diabetic rats.

BACKGROUND: Islet cell transplantation is a promising method to restore insulin independence to patients with type 1 diabetes mellitus. A main problem in clinical islet transplantation is the fact that only a small percentage of allogeneic islet-transplanted type 1 diabetic patients can completely omit insulin injections after transplantation. One reason for the impaired survival of islet grafts is aberration of the function of islets due to toxic agents, including oxygen radicals and nitric oxide, which arise during warm or cold ischemic time. Therefore, in clinical islet transplantation, islets have been preserved with a mixture of antioxidants to reduce free radical-mediated damage of transplanted beta cells. Our aim was to examine hepatic tissue after metabolic normalization following intraportal islet transplantation after application of sulforaphane. MATERIALS AND METHODS: Islets were isolated from pancreata of WAG rats. Sulforaphane (24 mg/kg) was administered 24 hours before isolated islets were transplanted into the liver through the portal vein (1200 +/- 100 per rat). At 9 months after transplantation the animals were killed and liver tissue removed for morphological examination. RESULTS: This report indicated that the intrahepatic portal vein site was indeed an excellent locus for implantation of free pancreatic islets. The islet grafts developed rich vascularization derived from both venous and arterial sources. The islet cells maintained their structural and functional integrity after implantation. CONCLUSION: Our results showed that sulforaphane improved islet function in vivo, indicating that combination of a free radical scavenger and an antioxidant (sulforaphane) may be used to increase the effectiveness of islet transplantation.

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PubMedDate not supplied

Regulation of apoptosis: involvement of Bcl-2-related proteins.

This article is a concise review of up-to-date information and recent discoveries concerning structure, site of action, tissue distribution, biological effects and molecular mechanisms of Bcl-2 family proteins. Particular attention has been focused on the physiological aspect of Bcl-2 protein function with emphasis on animal production and health. Bcl-2-related proteins are the principal regulators of apoptosis, acting through the control of ions (K+, H+, Cl-, Ca2+) and reactive oxygen species fluxes, the release of apoptogenic factors from mitochondria (AIF, cytochrome c) and the activation of the executors of apoptosis (caspases, DNases). The response of Bcl-2 proteins to pro- and anti-apoptotic signals relies on the activation of transcription and translation, phosphorylation, proteolytic cleavage, interactions with Bcl-2-related and other (structurally unrelated) proteins, translocation from the cytosol to intracellular membranes, and formation of permeability transition pores.

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PubMedDate not supplied

Induction of apoptosis and NF-kappaB by quercetin in growing murine L1210 lymphocytic leukaemic cells potentiated by TNF-alpha.

Polyphenol quercetin induced apoptosis in proliferating murine L1210 lymphocytic cells. DNA damage, as well as apoptosis and withdrawal from the cell cycle were transient. The above mentioned death promoting activity of quercetin was enhanced by physiological concentrations of TNF-alpha. At the same time, indices of cell viability dropped. However, the extent and tendency of the initially enhanced cell mortality steadily diminished throughout the experiment. After 12 h the G2/M phase reappeared. After 24 h all indices almost returned to control levels indicating either the selection of subpopulation of unaffected leukaemic cells or cells developing resistance to the treatment. A DNA ladder of oligonucleosomes was observed for apoptogenic treatments. We conclude that quercetin unmasked cell death, promoting the activity of TNF-alpha. However, after 12 and 24 h of exposure, surviving cells could complete the cell cycle and finally recover. At the same time, increased NF-kappaB activation was demonstrated by immunoblotting of the immunoreactive RelA/p65 subunit in nuclear extracts. Exposure to TNF-alpha or quercetin was crucial for increased activity of NF-kappaB, which may implicate an increasing resistance to their cytotoxicity.

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PubMedDate not supplied

Metabolic effect of orotic acid in calves.

Eight calves (males, Black and White crossbred with Holstein-Fresian) were fed milk and milk replacer without (control group) or with potassium orotate (3 mmol./l.) supplementation for 6 weeks after birth. Orotate depressed the biosynthesis of polyamines in mucosa of the gastrointestinal tract (rumen, omasum, abomasum, colon) by decreasing of ornithine decarboxylase activity with a simultaneous compensatory increase of S-adenosyl-methionine decarboxylase activity. A lower concentration of spermidine and spermine in the mucosa of the colon was also noted. The above changes were accompanied by increased urinary excretion of ornithine and arginine. Calf adaptation to a high OA intake was associated with an increased activity of the OA metabolizing enzyme complex (orotate phosphoribosyl transferase and orotidine monophosphate decarboxylase) in the liver, while urinary OA losses diminished with age. Increased concentrations of uracil and uridine in the liver and higher urinary excretion of pseudouridine in OA-fed calves was also observed. Stimulation of pyrimidine metabolism by OA depressed purine synthesis, which was reflected by a decrease of urate, hypoxanthine, and xanthine concentration in the liver. Interestingly OA enhanced urate excretion by the kidneys. OA strongly affected lipid metabolism in calves because total cholesterol, LDL-, and HDL-cholesterol, and triglycerides in blood plasma decreased while triglycerides accumulated in the liver of OA-fed calves. Milk OA in concentrations characteristic of cows with hereditary orotic aciduria exerts an unfavourable effect on the metabolism of polyamines, purines, and lipids in calf tissues.

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