In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms.

The metabolic fate of tributyltin and triphenyltin may contribute to the toxicity of these chemicals. We used human hepatic cytochrome P-450 (CYP) systems to confirm the specific CYP(s) involved in the in vitro metabolism of tributyltin and triphenyltin. There were no significant sex differences in the metabolic pattern of tributyltin or triphenyltin, indicating that the CYP(s) responsible for the metabolism of these chemicals in humans is/are not sex-specific form(s).

Acute toxic effects of dioctyltin on immune system of rats.

In the present study, dioctyltin chloride (DOTC: 100mg/kg, BW) was orally administered to immature (30-day-old) male rats, and the acute toxic effects were studied. Di- and monooctyltin (its metabolite) accumulations were mainly detected in the liver, and peaked 48h later. A similar pattern was also found in the kidney, but the levels were low or trace amounts.

Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na+ and Ca2+ and PKA-independent increase of cytosolic Ca2+ associated with insulin secretion in hamster pancreatic beta-cells.

Oral administration of triphenyltin chloride (TPT) (60 mg/kg body weight) inhibits the insulin secretion by decreasing the cytoplasmic Ca2+ concentration ([Ca2+]i) induced by glucose-dependent insulinotropic polypeptide (GIP) in pancreatic beta-cells of the hamster. To test the possibility that the abnormal level of [Ca2+]i induced by TPT administration could be due to a defect in the cAMP-dependent cytoplasmic Na+ concentration ([Na+]i) in the beta-cells, we investigated the effects of TPT administration on the changes of [Na+]i induced by GIP, glucagon-like peptide-1 (GLP-1), or forskolin, an activator of adenylyl cyclase, and on the changes of [Na+]i or [Ca2+]i induced by 6-Bnz-cAMP, an activator of protein kinase A (PKA), and 8-pCPT-2'-O-Me-cAMP, an activator of Epac. The [Na+]i and [Ca2+]i were measured in islet cells loaded with sodium-binding benzofuran isophthalate (SBFI) and fura-2, respectively.

Clinical and radiographic results of expansive lumbar laminoplasty in patients with spinal stenosis.

Background: In 1981, we developed a technique of expansive lumbar laminoplasty to alleviate the problems of conventional laminectomy in the treatment of spinal stenosis. The purposes of this study were to assess the long-term outcome following expansive lumbar laminoplasty and to investigate the postoperative problems.

Methods: Fifty-four patients underwent expansive lumbar laminoplasty for the treatment of spinal stenosis.

Sex difference in the principal cytochrome P-450 for tributyltin metabolism in rats.

Tributyltin is metabolized by cytochrome P-450 (CYP) system enzymes, and its metabolic fate may contribute to the toxicity of the chemical. In the present study, it is examined whether sex differences in the metabolism of tributyltin exist in rats. In addition, the in vivo and in vitro metabolism of tributyltin was investigated using rat hepatic CYP systems to confirm the principal CYP involved.

Clinical and radiographic results of expansive lumbar laminoplasty in patients with spinal stenosis.

Background: In 1981, we developed a technique of expansive lumbar laminoplasty to alleviate the problems of conventional laminectomy in the treatment of spinal stenosis. The purposes of this study were to assess the long-term outcome following expansive lumbar laminoplasty and to investigate the postoperative problems.

Methods: Fifty-four patients underwent expansive lumbar laminoplasty for the treatment of spinal stenosis.

Identification of principal cytochrome P-450 in triphenyltin metabolism in rats.

The in vivo and in vitro metabolism of triphenyltin using rat hepatic cytochrome P-450 (CYP) systems was investigated to confirm the specific CYP that is closely related to triphenyltin metabolism. No significant sex differences occurred between the in vivo and in vitro metabolic patterns of the chemical, indicating that the principal CYP for triphenyltin metabolism in rats is not a sex-specific form of CYP. In addition, seven types of complementary DNA (cDNA)-expressed rat CYPs, typical phenobarbital (PB)-inducible forms and the CYP2C subfamily were tested to determine the activity of triphenyltin metabolism.

Mammalian D-aspartyl endopeptidase: a scavenger for noxious racemized proteins in aging.

The accumulation of D-isomers of aspartic acid (D-Asp) in proteins during aging has been implicated in the pathogenesis of Alzheimer's disease, cataracts, and arteriosclerosis. Here, we identified a specific lactacystin-sensitive endopeptidase that cleaves the D-Asp-containing protein and named it D-aspartyl endopeptidase (DAEP). DAEP has a multi-complex structure (MW: 600kDa) and is localized in the inner mitochondrial membrane of mouse and rabbit, but DAEP activity was not detected in Escherichia coli, Saccharomyces cerevisiae, and Caenorhabditis elegans.

Glucagon-like peptide-1 induces a cAMP-dependent increase of [Na+]i associated with insulin secretion in pancreatic beta-cells.

Glucagon-like peptide-1 (GLP-1) elevates the intracellular free calcium concentration ([Ca2+]i) and insulin secretion in a Na+-dependent manner. To investigate a possible role of Na ion in the action of GLP-1 on pancreatic islet cells, we measured the glucose-and GLP-1-induced intracellular Na+ concentration ([Na+]i), [Ca2+]i, and insulin secretion in hamster islet cells in various concentrations of Na+. The [Na+]i and [Ca2+]i were monitored in islet cells loaded with sodium-binding benzofuran isophthalate and fura 2, respectively.

Metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes.

Tributyltin and triphenyltin are metabolized by cytochrome P-450 system enzymes, and their metabolic fate may contribute to the toxicity of the chemicals. In the current study, the in vitro metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes was investigated to elucidate the metabolic competence for these compounds in humans. The metabolic reaction using microsome-NADPH system that is usually conducted was not applicable to in vitro metabolism of organotins, especially triphenyltin.

Metabolism of a tetraphenyltin compound in rats after a single oral dose.

The metabolism of tetraphenyltin in rat liver and kidney has been examined. Tetraphenyltin and its metabolites in the tissue were determined periodically for 96 h after a single oral dose of 55.4 mg kg(-1) of tetraphenyltin by gas chromatography.

The association of lumbar disc disease with vitamin-D receptor gene polymorphism.

Background: Although the etiology of lumbar disc disease is unknown, it has been suggested that a genetic factor contributes to its development. Recently, some genetic polymorphisms have been found to be related to clinical disorders. We investigated the association between vitamin-D receptor gene and estrogen receptor gene polymorphisms and lumbar disc disease in young adults.

Glucose intolerance induced by a high-fat/low-carbohydrate diet in rats effects of nonesterified fatty acids.

We examined the time course of effects of a high-fat/low-carbohydrate (HF/LC) diet on the impairment of glucose tolerance in rats, clarified whether insulin secretion and sensitivity were impaired by the HF/LC diet, and investigated the relationship between the increased nonesterified fatty acids (NEFA) after HF/LC diet feeding and insulin secretion and sensitivity. We found that glucose tolerance and the postglucose-loading insulin secretion were impaired after 3 and 7 d on the HF/LC diet. The glucose intolerance was accompanied by a rise in the fasting plasma NEFA level.

Hypoglycemic and hypotriglyceridemic effects of tolbutamide in triphenyltin chloride-induced diabetic rabbits.

Triphenyltin (TPT) induces transient hyperglycemia and hypertriglyceridemia in rabbits and hamsters through inhibition of the insulin release stimulated by glucose. The disturbed site in TPT-diabetes is a result of signal transduction occurring before the voltage-dependent Ca2+ channel. The ATP-sensitive K channel (KATP channel) is located immediately at the upstream signal of voltage dependent Ca2+ channels on the signaling pathway of insulin secretion.