Biochemical medicine最新文献

Hyperthyroid rat heart was studied with the purpose of identifying the mechanism for the significant decrease in total creatine (free creatine plus phosphocreatine) observed in this pathology and its consequences on heart function. Administration of l-thyroxine in doses of $\text{50–100 μ}\text{g}\text{100}\text{g}$ of body weight during a week resulted in a reversible decrease of the total creatine by 40–50%. Simultaneously, remarkable changes in the creatine transport system across the cardiac cell membranes were observed: both the maximal rate of its active uptake and its passive movement along its concentration gradient were enhanced. In euthyroid hearts, the parameters of creatine uptake (K_m ⋍ 0.05 mm, V_max = 20 nmole/min/g dry weight) were similar to those for skeletal muscle and the passive movement of creatine was negligible. In hyperthyroid hearts the latter rate was enhanced to 0.4 μmole min/g dry weight, this showing reversible damages in the cell membrane structure induced by l-thyroxine. This conclusion is consistent with observed penetration of colloidal lanthanum into the cells of hyperthyroid hearts. Perfusion of hyperthyroid rat hearts with 50 mm creatine significantly restored creatine content in the cells. Hyperthyroid hearts with decreased creatine content were found to develop ischemic contracture more rapidly and in higher extent than the euthyroid hearts. Increased sensitivity to ischemic damage may be related to decreased efficiency of energy channeling via phosphocreatine pathway.

A comparison was made of succinyladenylate lyase (SAMP lyase), total serum sialic (TSA), and lipid soluble serum sialic acid (LSA) as early markers of malignancy in three experimentally induced rat tumor models. Elevation of SAMP lyase in 3′-methyl-dimethylaminoazobenzene-induced hepatic tumors at 2 weeks corresponded with microscopic detection of preneoplastic lesions with elevation of LSA occurring 2 weeks later. Elevation of breast SAMP lyase concurred with macroscopic presence of dimethylbenzanthracene involved breast tumors with elevation of LSA occurring 12 weeks later. Neither colon SAMP lyase nor LSA increased in rats bearing colon tumors induced by dimethylhydrazine. The determination of TSA was not a reliable indicator of tumor presence for the three types of tumors investigated. Both SAMP lyase and LSA are very good early indicators of hepatic tumor with SAMP lyase an earlier indicator of breast tumor than LSA.

A method has been developed for the separation of leucine, 2-ketoisocaproic acid, isovaleryl CoA, 3-methylcrotonyl CoA, 3-hydroxy-3-methylglutaryl CoA, 3-methylglutaconyl CoA, acetyl CoA, and acetoacetic acid by ion-exchange high-performance liquid chromatography. The analysis requires 180 min. Use of this method to assess the catabolism of radiolabeled leucine in normal cultured human skin fibroblasts shows that these cells do not accumulate CoA esters, but convert leucine mainly to 2-ketoisocaproic acid, glutamate, and hydroxyisovalerate. In the fibroblasts of a patient with maple syrup urine disease, only 2-ketoiscaproic acid is produced from leucine.

The effect of 5-km noncompetitive swimming (moderate exercise) and 2-km competitive speed swimming (intensive exercise) on protein breakdown was studied in a group of young male volunteers (16–20 years old) who followed a 3-MH-free diet throughout the study. Urinary 3-MH and creatinine were determined over a period of 24 and 48 hr as an index of protein degradation. Basal 3-MH levels in the two groups of swimmers were 2.85 and 3.07 μmole × kg⁻¹ × day⁻¹. Mean rates of 3-MH excretion were, respectively, 1.54 and 1.94 μmole × kg⁻¹ × day⁻¹ for the 48 hr after moderate exercise and the 24 hr after intensive exercise. The decrease in 3-MH urinary excretion was still evident when calculated as the urinary 3-MH-to-creatinine ratio.

Proline transport into renal brushborder membrane vesicles isolated from human kidney is mediated by two uptake systems. The high-affinity system is stimulated by a Na gradient and appears to be shared with glycine while the low-affinity system is not. Uptake curves of low concentrations of proline exhibit a Nagradient-dependent overshoot indicative of electrogenic transport. The proline transport systems observed in isolated human renal brushborder membrane vesicles appear to have characteristics similar to those in rat kidney membranes.

The effect of ingestion of water containing 20% ethanol for 1–2 months on lipid peroxide levels of liver, plasma, and erythrocyte was investigated in rats. Our results show that elevated plasma lipid peroxide levels and erythrocyte susceptibility to lipid peroxidation may reflect stimulated lipid peroxidation in rat liver following chronic ethanol ingestion.

A single intraperitoneal injection of 5 mg (250 mg/kg body wt) streptozotocin induced overt diabetes within 48 hr in male, 6-week-old mice of $\text{C57BL}\text{6}$ and $\text{C57BL}\text{10}$ (sensitive) strains. The $\text{C3H}\text{HeJ}$ and $\text{C3H}\text{eb}$ (resistant) strains exhibited a progressive delayed-onset hyperglycemia which required 6 weeks to reach the level seen within only 48 hr in sensitive strains. Resistance to SZ-induced diabetes was not related to changes in body weights or different pharmacokinetics of the drug. $\text{C3H}\text{HeJ}$ (resistant) mice showed a smaller fall in immunoreactive insulin pancreatic content and less severe damage of pancreatic islets on histologic examination, when compared to $\text{C57BL}\text{6}$ (sensitive) mice during the first week post-SZ. These results suggest that strain-related resistance to SZ-induced diabetes may be mediated at the level of the β cell's responsiveness to the cytotoxic action of the drug. This very simple experimental tool may be of value in monitoring the period before the onset of overt insulin-deficient diabetes and for probing the nature of factors that constitute a genetically resistant pancreas, understanding of which could aid management of diabetes mellitus in humans.