The effect of allopurinol on interstitial purine metabolism and tissue damage in skeletal muscle I-R injury

The causes and manners of death in medico-legal cases from a five-year period were examined. Alcoholics died more often of combined alcohol/drug intoxication and of carbon monoxide poisoning. They had a lower frequency of heart diseases, and there was no support for the existence of an alcoholic heart muscle disease. Lobar pneumonia was only found in alcoholics. There were, as expected, higher frequencies of the known alcohol-related diseases such as hepatic coma, bleeding oesophageal varices and alcohol intoxication. An observed higher frequency of death before the age of 35 could be attributed to alcohol-related diseases. The manners of death showed surprisingly small differences, as the main finding was a higher frequency of alcoholics with undeterminable manner of death.     

Anti-atherosclerotic action of angiotensin converting enzyme II. Effect on metabolism of kinin, free radical reaction, sensitivity to insulin and lipid metabolism

Blockade of the renin-angiotensin system reduces the development of the atherosclerotic process after vascular injury and in hyperlipidemic animals. ACE-inhibitors inhibit vascular smooth muscle cells migration and proliferation, macrophage-foam cell accumulation and preserve the antiaggregatory and antithrombotic function of the endothelium in atherosclerotic vessels. In addition to the inhibition of angiotensin II synthesis, reduced degradation of kinins and improvement of insulin action after ACE-inhibition may be responsible for observed actions. ACE-inhibitors may have also influence on lipids metabolism, including low density lipoprotein oxidation. Despite this, ACE-inhibitors failed to prevent restenosis after coronary angioplasty in humans. One reason for the lack of ACE-inhibitors effect in human restenosis might depend on the activation of the alternative angiotensin II-generating system in human arteries after vascular injury.     

Genetic analysis of purine metabolism in Leishmania donovani

To dissect the contributions of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase (APRT), and adenosine kinase (AK) to purine salvage in Leishmania donovani, null mutants genetically deficient in HGPRT and/or APRT were generated by targeted gene replacement in wild type cells and preexisting mutant strains lacking either APRT or AK activity. These knockouts were obtained either by double targeted gene replacement or by single gene replacement followed by negative selection for loss-of-heterozygosity. Genotypes were confirmed by Southern blotting and the resultant phenotypes evaluated by enzymatic assay, resistance to cytotoxic drugs, ability to incorporate radiolabeled purine bases, and growth on various purine sources. All mutant strains could propagate in defined growth medium containing any single purine source and could metabolize exogenous [3H]hypoxanthine to the nucleotide level. The surprising ability of mutant L. donovani lacking HGPRT, APRT, and/or AK to incorporate and grow in hypoxanthine could be attributed to the ability of the parasite xanthine phosphoribosyltransferase enzyme to salvage hypoxanthine. These genetic studies indicate that HGPRT, APRT, and AK, individually or in any combination, are not essential for the survival and growth of the promastigote stage of L. donovani and intimate an important, if not crucial, role for xanthine phosphoribosyltransferase in purine salvage.     

Changes in adenine nucleotide and mitochondrial metabolism of the kidney of burned rats and their relation to insulin

In rats with third-degree burns, the blood glucose level increased remarkably, with a concomitant suppression of insulin secretion from the pancreas after an oral glucose load. The energy charge (ATP + 1/2 ADP/ATP + ADP + AMP) levels of the kidney decreased to 0.659 as compared with 0.858 of controls at 8 hr after the burn (p less than 0.001). The phosphorylative activity of the kidney mitochondria fell to one third of controls at 8 hr after the burn (p less than 0.001), and that of heart mitochondria decreased to approximately 70% (p less than 0.005); the fall in liver and brain was less remarkable. The decrease in mitochondrial phosphorylative activity was accompanied by a reduction in the respiratory control ratio, P/O ratio, and state 3 respiration. The concentrations of cytochrome a(+a3) in the kidney mitochondria decreased to 69.9% of controls at 8 hr after the burn (p less than 0.001), those of cytochrome b to 82.6%, and those of cytochrome c + c1 to 75.3% (p less than 0.001). The decreased energy charge and oxidative phosphorylation of the kidney in burned rats were remarkably restored by subcutaneous administration of insulin. It is suggested that a reduction in insulin secretion from the pancreas may play an important role in initiating an impairment of adenine nucleotide and mitochondrial metabolism of the kidney.     

Children's motivational perception as related to the instrumentality and effect of action.

On the basis of F. Heider's (1958) balance conceptions, a model was developed for specifying relations between the perceived properties of an act (its instrumentality and its consequentiality) and the intentionality attributed to the act. 129 1st-, 4th-, and 6th-graders made intentionality judgments of actions described in 10 pairs of stories, each pair made up of contrasting actions varying in instrumentality and/or consequentiality. The older Ss adhered more closely to the naive psychological model both in intentionality choice and in the reasons for their choice. The 1st-graders had more difficulty judging intentionality on the basis of an act's instrumentality as compared to its consequentiality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effect of carbon monoxide and of hypoxic hypoxia. I. In vivo metabolism, distribution and action of hexobarbital

1. The biosynthesis of cholesterol was studied, by using various precursors, in rats subjected to several dietary regimes. 2. The use of 3H2O as a substrate to demonstrate differences in cholesterogenesis under various conditions was validated by using rats fed on cholesterol or cholestyramine. Cholesterol feeding resulted in decreased cholesterogenesis, whereas cholestyramine caused an increase. 3. With acetate as precursor, the biosynthesis of both digitonin-precipitable sterol and fatty acids was increased in vitro in response to a meal. 4. In rats fed ad libitum, hepatic cholesterogenesis was increased at midnight relative to mid-morning as measured by using acetate precursor in vitro. However, no such difference was found by using 3H2O in vivo. 5. The lipogenic response was measured in meal-fed rats by using 3H2O or octanoate in vivo. In contrast with findings with acetate in vitro, no postprandial stimulation of cholesterogenesis was seen with either 3H2O or octanoate as precursor, whereas fatty acid biosynthesis from either substrate was increased. 6. These findings are discussed with respect to current theories about the circadian rhythm of cholesterogenesis. Such theories are based on experiments using isolated enzyme measurements or non-physiological precursors such as acetate. 7. It is considered that results obtained with 3H2O give an accurate representation of cholesterogenesis under various conditions, and it is therefore suggested that hepatic cholesterogenesis in rats is not subjected to the same degree of diurnal rhythm as has previously been believed.     

Modifications to the rate of wound contraction by allopurinol

The effect of allopurinol (50 mg/kg) on the rate of full thickness excisional wound contraction in the Hooded Lister rat was assessed by planimetric and histological examinations. Compared with control animals, those treated with allopurinol showed a significantly lower coefficient of wound area contraction for days 0-7 (p < 0.05) than those of control animals. Histologically, in the allopurinol treated wounds the granulation tissue was less cellular but appeared to contain more collagen. This inhibition by allopurinol of the contraction phase of wound healing associated with an increased quantity of granulation tissue suggests that mediation of the process may involve a complex interaction between the fibroblasts/myofibroblasts and free radicals.     

Mammalian transcobalamin II metabolism. The immunological and the biological cross-reactivity of mammalain transcobalamin II

Assay of the reactivity between the chicken anti-rabbit transcobalamin II antiserum and the sera of 19 vertebrate species was carried out by both immuno-diffusion and Sephadex G-200 gel filtration column chromatography. Mammalian transcobalamin II cross-reacted with the antiserum whereas the serum vitamin B-12 binders of the bird, amphibian reptile and fish did not. The biological activity of the purified rabbit transcobalamin II was assessed using reticulocytes or erythrocytes of human, rabbit, guinea pig and rat. The purified rabbit transcobalamin II promoted the uptake of vitamin B-12 by the cells but showed a great variation in its activity. It is suggested that the rabbit transcobalamin II is immunologically and biologically similar to the serum transcobalamin II of the mammalian species studied.     

Tool use and the effect of action on the imagination.

Three studies examined the claim that hand movements can facilitate imagery for object rotations but that this facilitation depends on people's model of the situation. In Experiment 1, physically turning a block without vision reduced mental rotation times compared with imagining the same rotation without bodily movement. In Experiment 2, pulling a string from a spool facilitated participants' mental rotation of an object sitting on the spool. In Experiment 3, depending on participants' model of the spool, the exact same pulling movement facilitated or interfered with the exact same imagery transformation. Results of Experiments 2 and 3 indicate that the geometric characteristics of an action do not specify the trajectory of an imagery transformation. Instead, they point to people's ability to model the tools that mediate between motor activity and its environmental consequences and to transfer tool knowledge to a new situation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. II. Serum lipid levels

The response of lipids in the blood between two groups of six young women was compared. Group 1 took oral contraceptives and group 2 had never taken oral contraceptives. Two experimental diets supplied about 13% of the calories from protein, 36% from fat, and 51% from carbohydrate. Of the carbohydrate, 84% was either sucrose or wheat starch. Each diet was fed for 4 weeks in a cross-over design. In the portion of the research presented here, subjects were fed a high sucrose meal before each dietary period and after weeks 1 and 3 of each dietary period. Blood lipids were measured before and 30, 60, 120, and 180 min after each meal. Cholesterol and lipoproteins were not affected by the sucrose meal, but free fatty acid levels decreased significantly in both groups. The serum levels of triglycerides, beta-lipoproteins, and cholesterol were significantly higher in users than in nonusers of oral contraceptives. Free fatty acid levels were affected by an interaction between diet and time, and the decrease in response was greater after the sucrose than after the wheat starch diet. Triglycerides, cholesterol, and total lipids were not significantly different after the two carbohydrate diets.     

A new experimental in vitro culture medium for cultivation of Leishmania species

A new liquid culture medium prepared with chemicals that can be obtained economically and commercially was tested in in vitro cultivation of Leishmania promastigotes to obtain a large number of organisms to use in serological studies. The number of Leishmania infantum and Leishmania tropica promastigotes taken from Novy-MacNeal-Nicolle (NNN) medium reached 1 x 10(7)/ml at the end of the 8th day in our new medium, though in NNN medium the number of organisms reached only 5 x 10(6)/ml. After 10 subsequent passages, the culture medium prepared was evaluated as being quite inexpensive, simple, and successful compared with other commercially available liquid culture media.     

Role of the adenylate deaminase reaction in regulation of adenine nucleotide metabolism in Ehrlich ascites tumor cells

The regulatory properties of adenylate deaminase (EC 3.5.4.6) from Ehrlich ascites tumor cells suggest that the reaction catalyzed by this enzyme serves to protect the cell against sharp decreases in the adenylate energy charge by removing adenosine 5'-monophosphate generated when the rate of utilization of adenosine triphosphate is suddenly increased. The enzyme is effectively inhibited under normal physiological conditions of high energy charge (0.9) and 4 to 5 mM adenine nucleotide pool size. The reaction is sharply activated by a decrease in the energy charge in the physiological range (0.9 to 0.6). At low energy charge (0.6), decrease in the size of the pool causes a marked and nonlinear decrease in the rate of the deaminase reaction. This effect presumably serves to prevent excessive depletion of the adenine nucleotide pool. Calculations based on the kinetic data obtained in this study show that the AMP deaminase reaction can account for the well-established alteration of adenine nucleotide metabolism that is observed following addition of glucose or 2-deoxyglucose to intact ascites cells.     

Strain differences in adrenal CYP2D16 expression in guinea pigs. Relationship to xenobiotic metabolism

Experiments were done to determine the mechanisms responsible for differences in adrenal microsomal xenobiotic metabolism between Strain 13 and English Short-Hair (ESH) guinea pigs. The rates of adrenal xenobiotic metabolism (bufuralol 1'-hydroxylase, benzo[a]pyrene hydroxylase, benzphetamine N-demethylase) were 2-3 times greater in microsomes from the Strain 13 animals. In both strains, xenobiotic-metabolizing activities were far greater in the inner zone (zona reticularis) than in the outer zones (zona fasciculata and zona glomerulosa) of the adrenal cortex. Northern blot analyses of total adrenal RNA with a CYP2D16 cDNA as the probe revealed significantly greater amounts of CYP2D16 mRNA in the Strain 13 guinea pigs. In addition, SDS-PAGE and Western blotting of adrenal microsomes demonstrated higher concentrations of CYP2D16 protein in Strain 13 than in ESH animals. Expression of CYP2D16 was predominantly in the inner zone of the adrenal, coinciding with the major site of xenobiotic metabolism. The results demonstrated higher levels of expression of CYP2D16 in adrenal glands from Strain 13 than from ESH guinea pigs, which may account for the strain differences in adrenal xenobiotic metabolism. Strain 13 guinea pigs should serve as a good experimental model for further studies on the regulation of adrenal CYP2D16.