bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Oxidative Phosphorylation in Liver of Protein-Energy Malnourished Rats
Authors: Ramanadham M. , Kaplay S.S.
Published: November 2008

State 3, state 4 respiratory rates, respiratory control ratio (RCR = state 3/state 4), ADP/O ratio and swelling in salt medium were determined in liver mitochondria from three groups of rats: group 1 – controls; group 2 – energy-restricted, and group 3 – protein-deficient. Experiments were carried out between 3 and 5 weeks and between 7 and 9 weeks after initiation of the experimental diets. State 3 respiration of mitochondria from group 2 rats was reduced after 3-5 weeks on the experimental diet as compared to group 1 rats. However, state 4 respiration, RCR and ADP/O ratio were not different in groups 2 and 3 as compared to those in controls. Between 7 and 9 weeks it was found that state 3 respiration with both the substrates was higher in groups 2 and 3 as compared to group 1. State 4 respiration was increased in group 2 but was unaltered in group 3, compared to controls. Mitochondrial preparations from group 2 rats showed faster rates of swelling in KC1 medium, compared to group 1, at both periods. On the other hand, the rates of swelling were slower as compared to controls in the case of mitochondria isolated from group 3 rats. Results of these experiments indicate that the terminal effect of severe restriction of calories and protein on mitochondrial oxidative phosphorylation is similar.
Veränderungen der Retention von Zink im Organismus während der Gravidität
Authors: Schneider Ursula.A. , Kirchgessner M.
Published: November 2008

Enhanced retention of nutrients in the gravid organism, which exceeds the normal deposition in the reproductive organs and in fetuses, is called ‘pregnancy anabolism’. For zinc this superretention could be established only in the liver which was enlarged in gravid rats, too. In all other tissues of gravid animals, zinc contents were lower compared with nongravid rats. After lactation, these changes in zinc status were equalized, and gravid and nongravid animals showed the same values.
Effects of Exercise on Plasma and Liver Lipids of Rats
Authors: Fukuda Nobuhiro , Ide Takash , Kida Yoshitaka , Takamine Kazuhiro , Sugano Michihiro
Published: November 2008

The effects of treadmill exercise on hepatic cholesterogenesis and fecal steroid excretion were studied using male Wistar rats fed a commercial pellet ration. Exercise, in comparison with ad libitum or pair-feeding sedentary groups, caused the following significant changes: (i) a reduction in the concentration of plasma triglyceride, phospholipid and cholesterol; (ii) a reduction in liver weight; (iii) increases in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and incorporation of mevalonate into digitonin precipitable sterol; (iv) increases in excretion of neutral and acidic steroids into the feces; (v) the increase in lipoprotein lipase activity in the cardiac muscle, and (vi) the decrease in the concentration of carcass triglyceride but not of cholesterol. These data suggest that the mechanism responsible for the plasma cholesterol-lowering effect of exercise is attributable to an increase in excretion of fecal neutral and acidic steroids accompanied by an acceleration of cholesterol turnover in the body.
Über die cholesterinsenkende Wirkung der einzelligen Grünalge Scenedesmus acutus 276–3a
Authors: Rolle Ingrid , Pabst Wolfgang
Published: November 2008

In three series of experiments hypercholesterolemia was induced in male Sprague-Dawley rats by a 3% cholesterol-enriched diet. The development of hypercholesterolemia was considerably retarded when 20% Scenedesmus powder was incorporated in the diet. In animals fed with standard diet and cholesterol for 6–8 weeks, the average concentration of blood plasma cholesterol increased from 2.0 to 3.6 mmol/l. In contrast, the final concentration reached only 2.4–2.8 mmol/l in animals receiving the cholesterol diet with algae. The plasma cholesterol level in animals receiving only an algal diet did not appear to be influenced. The mean value at the beginning of the test was 2.0 and 2.2 mmol/l at the end. The level of plasma triglyceride in animals fed on algae with and without the addition of cholesterol was lower than that of the controls. The algae-enriched diet prevented an excessive deposition of cholesterol in the liver. The increase in weight of the livers of rats receiving the cholesterol-enriched standard diet and the cholesterol-enriched algal diet were 2.0 and 0.8 g, respectively. The cholesterol content of the livers increased to 600 and 180 mg, respectively.
Influence of Cholecalciferol on Tissue Zinc Homeostasis in the Rat
Authors: Chausmer A.B. , Ward G. , Zears R.
Published: November 2008

A role for calciferol in zinc homeostasis was investigated by radioisotope uptake and compartmental analysis techniques. Cholecalciferol was injected into rats 4–5 days prior to radioisotopic study of rapidly exchangeable pools ( < 4 h). Kidney, liver, and duodenum had significant increases in zinc uptake rates. Bone and skeletal muscle had significant decreases. No other tissues had significant differences. Compartmental analysis models generated by the SAAM-25 digital computer program suggested a decrease in the fractional tissue to plasma coefficient to be the mechanism for the observed changes in the serum zinc concentration and tissue zinc accumulation rates. It is not clear whether this is a specific effect of calciferol on zinc homeostasis or is a nonspecific response which may reflect some role for zinc in calciferol metabolism.
Selenium in Premature Infants
Authors: Amin S. , Chen S.Y. , Collipp P.J. , Castro-Magana M. , Maddaiah V.T. , Klein S.W.
Published: November 2008

Premature infants have a lower selenium concentration in serum than full-term infants and children. The selenium concentration goes down quickly in infants treated for respiratory distress syndrome without supplementation. One premature infant with bronchopulmonary dysplasia had persistently low concentrations of selenium. Vitamin E supplements did not affect the serum selenium concentration in healthy premature infants. Supplementation with 3 µg/kg of selenium in parenteral fluids prevented the fall in the concentration seen in other infants not supplemented. Premature infants and especially those treated withoxygen may warrant selenium supplementation to the parenteral nutrition solution. Vitamin E supplements alone are apparently not sufficient to prevent selenium deficiency and potential oxygen toxicity.
Effect of Indigestible Polysaccharides on Protein Digestibility and Nitrogen Retention in Growing Rats
Authors: Harmuth-Hoene Anna-Elisabeth , Schwerdtfeger Eckehard
Published: November 2008

The effect of five indigestible polysaccharides (IP) of different origin and chemical structure on N balance and dry matter digestibility was studied in growing rats. The diets contained 10% of gum guar (GG), carob bean gum (CBG), Na-alginate (Na-A), agar-agar (AA) or carrageenan (C), respectively. Dry matter digestibility and apparent protein digestibility were significantly decreased below control values by all 5 IP. N retention was significantly lower after ingestion of AA or C. In the rats receiving GG, CBG or Na-A urinary N excretion was reduced, thus compensating for increased fecal N losses by these animals. The different effects of the 5 substances on N balance are attributed to their partial breakdown through the action of intestinal microflora and/or their ability to partially inhibit the activity of proteolytic enzymes in the gastrointestinal tract. Trypsin inhibition in vitro was observed for C only. Suitability of the various IP as bulking agents in reducing diets is discussed.
Forebrain Fatty Acid Composition during Development in Protein-Calorie and Essential Fatty Acid Deficiencies in the Rat
Authors: Karlsson Ingvar
Published: November 2008

Rats were fed three different dietary levels of essential fatty acids (EFA), 3.0, 0.75 and 0.1 cal%, representing normal, subnormal and severely deficient dietary intakes. From the animals kept on these diets, with a protein content of 16 cal%, 3-month-old females were randomly selected to be fed diets with only 6 cal% protein but with unchanged amounts of EFA. The rats were then mated, and the effects of the diets were studied in the forebrains of their offspring. The growth and the fatty acid patterns of the ethanolamine phosphoglyceride and total phosphoglyceride fractions were studied during the first 60 days of life. Addition of protein-calorie deficiency to rats severely undernourished in EFA mitigated the biochemical signs of EFA deficiency. In EPG the developmental pattern with a decrease of 20:4 (n-6) and an increase of 22:6 (n-3) was retarded between 11 and 21 days of age in the protein-calorie deficient groups suggesting a delay in the maturation of the forebrain.
The Effect of Progesterone on Fetal and Placental Development in Normal and Protein-Energy-Restricted Rats
Authors: van Marthens E. , Zamenhof S. , Firestone C.
Published: November 2008

Maternal protein-energy restriction (25% of the ad libitum intake) during the first 10 days of pregnancy resulted in severely altered fetal growth rates. Fetal development was assessed by body weight, brain weight, brain DNA, and brain protein content on fetal days 16, 18, 20 and at term. The individual placentas were also examined (weight, DNA and protein content) on each of these fetal days. Progesterone was administered commencing with day 3 of pregnancy until the day Caesarian section was done, in an attempt to rehabilitate placental development. This treatment did not improve placental development on fetal days 16 or 18. However, fetal development was significantly improved on day 16 and day 20, as compared to the dietary-restricted group without progesterone.
Adaptation to Restricted Intake of Protein and Energy
Authors: Khan Akmal , Bender A.E.
Published: November 2008

Adult rats that maintained nitrogen balance on a diet containing 5% casein fed ad libitum were restricted to 70% of their normal food intake for 31 days. This resulted in a negative N balance, loss of body weight and increased activities of hepatic glutamic pyruvic transaminase and arginase – all of which persisted for 10 days. After this time there was no further weight loss, the negative N balance returned to equilibrium and the activities of the two enzymes returned to normal indicating adaptation to the dietary restriction. Radio-isotope studies with labelled methionine showed that dietary restriction led to an increase in the radioactivity of the liver and a decrease of that of the muscles indicating maintenance of liver protein at the expense of muscle protein. Resting oxygen consumption decreased by 34% after 20 days of dietary restriction and this would account for the adaptation observed.
Zinc Status and Serum Levels of Retinol-Binding Protein, Tocopherol and Lower Density Lipoproteins in Male and Female Rats Fed on Semi-Purified Diets Containing Rapeseed Protein or Casein
Authors: Eklund Anders , Rask Lars
Published: November 2008

Experiments were carried out in order to evaluate the effect of various levels of dietary zinc supplementation on the zinc status, growth and contents of retinol-binding protein (RBP), tocopherol and lower density lipoproteins (VLDL + LDL) in serum of rats fed on diets containing rapeseed protein concentrate (RPC) or casein as the sole source of protein. In male rats fed on RPC diet at a 10% protein 5% fat level, a highly significant correlation was found between dietary zinc content and the total tibia zinc content (r = 0.946) in the dietary zinc range of 35–137 µg/g. In contrast, the casein rats attained almost maximal bone zinc contents even at the lower level of dietary zinc. No correlation was found between zinc status and the protein efficiency ratio obtained for the rapeseed protein.In female rats fed on a zinc-supplemented RPC diet at a 20% protein and 10% fat level, the serum levels of tocopherol and VLDL + LDL were reduced in comparison to the levels observed in female rats fed on a corresponding casein diet. No diet-related changes in serum levels of RBP were found. However, male rats showed significantly higher RBP values than the female rats.
Dietary Casein Levels and Taurine Supplementation
Authors: Loriette Claude , Pasantes-Morales Herminia , Portemer Christiane , Chatagner Fernande
Published: November 2008

Activities of cysteine dioxygenase (CO) and cysteine sulfinate decarboxylase (CSD) and the concentrations of taurine (T) in brain, liver and kidney of rats fed on diets containing 18% casein (A), 60% casein (B) and 17% casein supplemented with 1% of taurine (+T), were measured. Regardless of the diet, the three measurements were the same in the brains of the animals in the three groups. In the liver and the kidney, CO activity was also the same in all three diets, but a decrease of CSD activity associated to an increase of T was observed in rats fed on diet B. The taurine-supplemented diet led to an increase in T concentration.
Influence of Diet on Plasma Cholesterol Concentrations in Suckling and Weanling Rabbits
Authors: Roberts D.C.K. , Huff M.W. , Carroll K.K.
Published: November 2008

Rabbits were weaned to different semipurified diets to determine which characteristics of the diet were required to maintain the hypercholesterolemia of the suckling period. Gradual weaning to a diet similar in fat, cholesterol, protein and carbohydrate content to rabbit milk maintained and enhanced the hypercholesterolemia. Reduction of the cholesterol content, and to some extent the fat content of this diet, decreased the plasma cholesterol level, but the type of dietary protein did not alter the results. After weaning, however, animals fed milk protein (casein) in the absence of dietary cholesterol became hypercholesterolemic, whereas those fed plant protein (soy protein isolate) remained normocholesterolemic.
Evaluation of Urinary Alkaline Ribonuclease Activity in the Assessment of Subclinical Malnutrition in Weanling Rats
Authors: Whitear Susan.H. , Basu T.K.
Published: November 2008

The sensitivity of the hydroxyproline (OHP)/creatinine (Cr) index and the free urinary alkaline ribonuclease activity as indices of nutritional status have been compared using rats as an experimental model. The results have revealed that the OHP/Cr index is a better biochemical parameter than the urinary alkaline ribonuclease activity for indicating a subclinical degree of malnutrition.
Utilization of Protein at Sub-Maintenance Energy Intakes
Authors: Naismith D.J. , Holdsworth M.D.
Published: November 2008

Adult rats fed a diet containing 14%, by weight, of protein displayed a negative N balance when energy intake was reduced to a value approximating basal metabolism. A positive N balance was induced, however, by raising the protein concentration in the diet, and N retention continued until body fat reserves were almost exhausted. These findings are in conflict with the widely-held view that N equilibrium can be achieved only when the need for energy is satisfied.
Lysosomal Acid Phosphatase Decrease in Nutritional Encephalopathy in Chicks
Authors: Dror Yosef , Budowski Pierre
Published: November 2008

Encephalopathy was induced in 14-day-old chicks by a vitamin E-deficient diet containing 15% thermally oxidized safflower oil. Bound acid phosphatase activity in the cerebellum was markedly lower in affected chicks than in vitamin E-supplied control chicks. Free activity also tended to be lower in the deficient group. There were no differences in enzyme activities of cerebrum and liver between deficient and control chicks.
Effect of Folate Supplementation and Malaria on the Folate Content of Human Milk
Authors: Osifo ’;Bola O.A. , Onifade A.
Published: November 2008

The concentration of folate in human milk was estimated in two groups of lactating mothers. The first group had no folate supplementation throughout pregnancy and the other group had 5 mg folate/day throughout the last trimester. Concentration of folate was significantly higher in the milk of mothers who had supplementation. There was a significant increase in folate concentration as the milk progressed to maturity. When malaria was present, there was no significant increase in the concentration of folate in the milk. Human milk is low in folate, and a rise in body temperature seems to disturb folate metabolism.
Absorption and Retention of Magnesium and Some Trace Elements by Man from Typical Indian Diets
Authors: Rao Nageswara , Rao Narasinga
Published: November 2008

Availability of magnesium and some trace elements in Indian diets has been studied in human adults. Absorption of trace elements from the diets as a percentage of intake was: chromium 60, copper 18, magnesium 34, manganese 14 and zinc 16. Daily dietary intakes of 51.5 µg of chromium, 1.73 mg copper and 4.1 mg of manganese were found to be necessary to keep the subjects in balance in respect to these elements.
Body Lipids of Guinea Pigs Exposed to Different Dietary Fats from Mid-Gestation to 3 Months of Age
Authors: Pavey Diana E. , Widdowson Elsie M.
Published: November 2008

Pregnant guinea pigs were fed on one of three diets: a commercial low-fat diet or a high-fat diet containing either maize oil or beef dripping. The young were killed at birth, the brain removed and dissected into three regions; the cerebellum, cerebrum and stem. The fatty acid composition of the major phospholipid classes, phosphatidylcholine and phosphatidylethanolamine was determined using gas chromatography. Compared with those fed the commercial or beef dripping diet the brain of the young of mothers fed maize oil during pregnancy had an increased percentage of linoleic acid and of its long-chain derivatives arachidonic acid and docosapentaenoic acid and a lower percentage of docosahexaenoic acid. These changes occurred in both lipid classes and in all regions of the brain. The results demonstrate that the fatty acid composition of the brain lipids of newborn guinea pigs can be influenced by the nature of the maternal dietary fat consumed during the last weeks of pregnancy.
High and Low High-Density Lipoproteins: Clinical Implications
Authors: Avogaro P. , Cazzolato G. , Bon Bittolo , Quinci G.G.
Published: November 2008

High-density lipoproteins (HDL) are macromolecular complexes of lipids and proteins which float in the ultracentrifuge between densities of 1.063 and 1.21 g/l. A major division of HDL into two subclasses according to their specific density has been proposed: HDL2 (d= 1.063–1.125) and HDL3 (d= 1.125–1.21). The division is supported by the different proportions of lipids and apoproteins in the two subclasses and by evidence suggesting that the protective effect of HDL lies mostly in the HDL2 subclasses. Recent epidemiological, experimental and clinical data have supported a probable role or HDL as an anti-risk factor due to their negative correlation with the prevalence of ischaemic heart disease. Some of these data are presented and discussed in this paper.
Dietary Effects on Blood Pressure
Authors: Heyden S. , Hames C.G.
Published: November 2008

Low dietary potassium intake, particularly among black hypertensive patients, appears to contribute significantly to this disease and its major sequellae. The high sodium intake of industrialized societies and the epidemic prevalence of hypertension must be considered in the light of a relatively greater urinary potassium excretion as compared to a low-sodium diet with a lower urinary potassium excretion. There is no reason to assume that weight reduction per se is the major contributor to lowering of elevated blood pressure levels although claims to this effect have been made. In general, a high-caloric diet is loaded with sodium while a low-energy diet has a drastically reduced sodium content. The hypothesis that a higher dietary linoleic acid intake via increased prostaglandin synthesis may lead to natriuresis and a drop in blood pressure levels is an interesting development which needs more testing.
Dietary Effects on Certain Adrenal Cortical Functions in the Rat
Authors: Boyd G.S. , Gorban A.M.S. , Lawson Margaret E.
Published: November 2008

The rate-limiting step in adrenal steroidogenesis is associated with the mitochondrial-cytochrome-P450scc-dependent production of pregnenolone from cholesterol. This sterol side-chain cleavage reaction is influenced by the supply of cholesterol to the mitochondria. Cholesterol is stored as cholesterol esters while the cytosol contains a hormone-sensitive cholesterol ester hydrolase. This enzyme is activated by phosphorylation involving a cyclic AMP-dependent protein kinase and ATP; this enzyme preferentially attacks cholesterol oleate or cholesterol linoleate. The lipid composition of the adrenal cortex is influenced by diet so that animals on a low-fat diet tend to store cholesterol oleate and as the linoleate content of the diet is increased, the cholesterol linoleate content of the adrenal cortex increases. Animals maintained on a high erucate diet tend to store large amounts of cholesterol erucate in the adrenal cortex; such animals have an impaired adrenal cortical function. Animals maintained on a low-fat diet (marginally deficient in essential fatty acids), a linoleate-replete diet or a moderate erucate diet, all exhibited normal responses to ACTH and normal corticosterone production rates.
Pathophysiology of Long-Chain Polyene Fatty Acids in Heart Muscle
Authors: Gudbjarnason Sigmundur
Published: November 2008

The polyene fatty acid composition of cardiac phospholipids is modified by age, diet and stress in the rat. In the aging heart there is a progressive replacement of 18:2n6 by 20:4n6 in phosphatidylcholine (PC) and a replacement of 18:2n6 by 22:6n3 in phosphatidylethanolamine (PE). Norepinephrine stress accelerates aging of cardiac PC and PE. Dietary fish oil causes a replacement of 18:2n6 and 20:4n6 by 22:6n3 in cardiac PC and PE but not in cardiolipin. Studies on human cardiac autopsy samples suggest that: (a) polyene fatty acid composition changes with age; (b) stability of cardiac phospholipids is a function of the fatty acid composition, chain length and unsaturation; (c) coronary atherosclerosis is associated with a reduced content of 18:2n6 in phospholipids, an increased content of glycerides of abnormal composition and an unexpectedly low level of free fatty acids (FFA) in the heart muscle, and (d) many cases of sudden cardiac death in the absence of marked coronary artery stenosis or myocardial infarction may be associated with significant alterations in myocardial levels of FFA (↑) or PE (⇓).
The Role of Fat in Child Nutrition
Authors: Grande Francisco
Published: November 2008

The wide differences in fat content among the milks produced by different mammals seem to indicate that the fat requirements of the newborn are also different. Fat accounts for over 50% of the energy content of human milk. This relatively high fat content can be necessary to meet the baby’s high energy demands during the first weeks of life, when it has a reduced ability to adjust the volume of intake. Data from breast-fed babies showing satisfactory growth indicate that their fat intake up to 5–6 months of age is of the order of 34–45 g/day. Digestion and absorption of fat are influenced by the degree of saturation and molecular size of the fatty acids, and by the triglyceride structure. In general, fats rich in unsaturated fatty acids are better absorbed than saturated fats, both by children and adults. Short-chain fatty acids are better absorbed than those of greater molecular size, for an equal degree of saturation. Fats having most of their palmitic acid esterfied in position 2 are better absorbed than fats having this fatty acid randomly distributed among the three positions of the glyceride. The better absorption of human milk fat as compared to that of cow’s milk can be explained, at least in part, by the preferential esterification of palmitic acid in position 2 of the glycerides of human milk fat. Difficulties with fat absorption are particularly important in premature babies. These babies are able to absorb human milk fat to the extent of 80%, but have a smaller ability to absorb the fat from cow’s milk. Human milk has been shown to contain a lipase which is activated by bile salts and seems to be important for the digestion of milk lipids, particularly the esters of retinol. Current estimates of essential fatty acid (EFA) requirements by infants and children are of the order of 3 % of the total energy intake. This figure is lower than the EFA content of human milk generally reported, but higher than that of cow’s milk. There is no evidence that infants fed solely on cow’s milk during their first 4–5 months have clinical manifestations of EFA deficiency. However, bottle-fed babies tend to have lower EFA levels and higher ratios of trienes to tetraenes in their blood lipids, than breast-fed babies. Plasma cholesterol levels of infants and children are affected by the fatty acid composition of the dietary fat and the plasma cholesterol of brest-fed babies may be reduced by increasing the linoleic acid content of the mother’s milk. This role of fat is of obvious interest in child nutrition, in view of the emphasis currently laid on the early prevention of atherosclerosis. An analysis of this problem is, however, beyond the scope of this discussion.
Hypertension-Mediated Albuminuria Is Associated with Reduced Lysosomal Activity in the Kidney and the Heart
Authors: Hilliard Lucinda M. , Russo Leileata M. , Comper Wayne D.
Published: November 2008

Background: Recent studies suggest that expression of the transforming growth factor-β (TGF-β)-inducible gene-h3 (βig-h3) and its anti-lysosomal activity may be responsible for the development of albuminuria and cardiovascular disease associated with hypertension. Methods: We evaluated the proposed linkage using the spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat models. The kidney and left ventricular weight/body weight ratios were measured and cardiac collagen deposition was analyzed by Masson’s trichrome stain. Renal and cardiac TGF-β1 and βig-h3 expression were determined by real-time reverse transcription-polymerase chain reaction, and renal and cardiac cathepsin B and L activities were measured as an indicator of lysosomal proteolytic activity. Results: SHR exhibited increased levels of intact urinary albumin without significant change in total albumin (intact plus albumin-derived material) excretion. This was accompanied by renal hypertrophy, increased renal βig-h3 expression, and reduced renal cathepsin B and L activities. At the same time, increased cardiac TGF-β1 and βig-h3 expression and reduced cardiac cathepsin B activity was identified in SHR in addition to cardiac hypertrophy and increased collagen deposition. All these changes could be ameliorated with ramipril treatment. Conclusions: These findings implicate for the first time βig-h3 expression and lysosomal activity as a key factor in the induction of albuminuria and cardiovascular disease associated with hypertension.
Effects of Thyroid Hormones on the Multiple Molecular Forms of Mitochondrial Malate-Dehydrogenase
Authors: Varrone S. , Consiglio E. , Covelli I.
Published: November 2008

The effect of the thyroid hormones on the configurational state of mitochondrial malate-dehydrogenase has been investigated. A new, heavy form of malate-dehydrogenase (9 S) has been purified from pig-heart mitochondria. The physicochemical and chemical properties of this enzyme, compared with those of the well-known mitochondrial enzyme (5 S), show that 9S protein differs from the lighter form by: (a) content of sulfydryl groups, (b) the presence of tryptophan, (c) immunochemically. The configuration of this new form of malate-dehydrogenase appears to be that of a tetramer composed of two non-identical subunits. Low concentrations of thyroxine and iodine cyanide are able to dissociate the 9 S enzyme into smaller subunits whose sedimentation coefficients approximate 5 S. The disaggregation of the 9 S protein is coincident with an enhancement of the enzyme activity in the order of 50% over the initial value. The degree of activation is strongly influenced by the pH of incubation, the greatest effect being obtained at pH ranging between 7.0 and 7.4. One of the subunits, the ‘catalytic’, shows physico-chemical and immunochemical properties similar to those of the well-known mitochondrial enzyme (5 S). The other, ‘regulatory’ subunit, is devoided of enzyme activity and is immunochemically different from the ‘catalytic’ one. A scheme suggesting the allosteric effect of thyroxine in the regulation of malate-dehydrogenase activity is presented.
Mechanism of Hormonal Action
Authors: Snart Ronald S.
Published: November 2008

A review of evidence supporting a general mechanism of action of steroid hormones has been made by comparing the action of aldosterone in stimulating sodium transport across toadbladder, with corticosterone stimulation of gluconeogenic enzymes in rat liver and oestradiol binding in rat uterus. Related aspects of the mechanism of action of neurohypophyseal hormones have been considered in terms of the ‘pore’ and cyclic AMP theories.
Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4– and TGF-β1–Dependent Pathway
Authors: Sucosky Philippe , Balachandran Kartik , Elhammali Adnan , Jo Hanjoong , Yoganathan Ajit P.
Published: November 2008

Objective—

Hemodynamics has been associated with aortic valve (AV) inflammation, but the underlying mechanisms are not well understood. Here we tested the hypothesis that altered shear stress conditions stimulate the expression of cytokines and adhesion molecules in AV leaflets via a bone morphogenic protein (BMP)- and transforming growth fact (TGF)-β1–dependent pathway.

Methods and Results—

The ventricularis or aortic surface of porcine AV leaflets were exposed for 48 hours to unidirectional pulsatile and bidirectional oscillatory shear stresses ex vivo. Immunohistochemistry was performed to detect expressions of the 4 inflammatory markers VCAM-1, ICAM-1, BMP-4, and TGF-β1. Exposure of the aortic surface to pulsatile shear stress (altered hemodynamics), but not oscillatory shear stress, increased expression of the inflammatory markers. In contrast, neither pulsatile nor oscillatory shear stress affected expression of the inflammatory markers on the ventricularis surface. The shear stress–dependent expression of VCAM-1, ICAM-1, and BMP-4, but not TGF-β1, was significantly reduced by the BMP inhibitor noggin, whereas the TGF-β1 inhibitor SB431542 blocked BMP-4 expression on the aortic surface exposed to pulsatile shear stress.

Conclusions—

The results demonstrate that altered hemodynamics stimulates the expression of AV leaflet endothelial adhesion molecules in a TGF-β1– and BMP-4–dependent manner, providing some potential directions for future drug-based therapies for AV diseases.
Mitochondrial Regulation of Sarcoplasmic Reticulum Ca2+Content in Vascular Smooth Muscle Cells
Authors: Poburko Damon , Liao Chiu-Hsiang , van Breemen Cornelis , Demaurex Nicolas
Published: November 2008

Subplasmalemmal ion fluxes have global effects on Ca2+signaling in vascular smooth muscle. Measuring cytoplasmic and mitochondrial [Ca2+]and [Na+], we previously showed that mitochondria buffer both subplasmalemmal cytosolic [Ca2+] and [Na+] in vascular smooth muscle cells. We have now directly measured sarcoplasmic reticulum [Ca2+] in aortic smooth muscle cells, revealing that mitochondrial Na+/Ca2+exchanger inhibition with CGP-37157 impairs sarcoplasmic reticulum Ca2+refilling during purinergic stimulation. By overexpressing hFis1 to remove mitochondria from the subplasmalemmal space, we show that the rate and extent of sarcoplasmic reticulum refilling is augmented by a subpopulation of peripheral mitochondria. In ATP-stimulated cells, hFis-1–mediated relocalization of mitochondria impaired the sarcoplasmic reticulum refilling process and reduced mitochondrial [Ca2+] elevations, despite increased cytosolic [Ca2+] elevations. Reversal of plasmalemmal Na+/Ca2+exchange was the primary Ca2+entry mechanism following ATP stimulation, based on the effects of KB-R7943. We propose that subplasmalemmal mitochondria ensure efficient sarcoplasmic reticulum refilling by cooperating with the plasmalemmal Na+/Ca2+exchanger to funnel Ca2+into the sarcoplasmic reticulum and minimize cytosolic [Ca2+] elevations that might otherwise contribute to hypertensive or proliferative vasculopathies.
Ca
2+
-Independent Alterations in Diastolic Sarcomere Length and Relaxation Kinetics in a Mouse Model of Lipotoxic Diabetic Cardiomyopathy
Authors: Flagg Thomas P. , Cazorla Olivier , Remedi Maria S. , Haim Todd E. , Tones Michael A. , Bahinski Anthony , Numann Randal E. , Kovacs Attila , Schaffer Jean E. , Nichols Colin G. , Nerbonne Jeanne M.
Published: November 2008

Previous studies demonstrated increased fatty acid uptake and metabolism in MHC-FATP transgenic mice that overexpress fatty acid transport protein (FATP)1 in the heart under the control of the α-myosin heavy chain (α-MHC) promoter. Doppler tissue imaging and hemodynamic measurements revealed diastolic dysfunction, in the absence of changes in systolic function. The experiments here directly test the hypothesis that the diastolic dysfunction in MHC-FATP mice reflects impaired ventricular myocyte contractile function. In vitro imaging of isolated adult MHC-FATP ventricular myocytes revealed that mean diastolic sarcomere length is significantly (
P
<0.01) shorter than in wild-type (WT) cells (1.79±0.01 versus 1.84±0.01 μm). In addition, the relaxation rate (dL/dt) is significantly (
P
<0.05) slower in MHC-FATP than WT myocytes (1.58±0.09 versus 1.92±0.13 μm/s), whereas both fractional shortening and contraction rates are not different. Application of 40 mmol/L 2,3-butadionemonoxime (a nonspecific ATPase inhibitor that relaxes actin–myosin interactions) increased diastolic sarcomere length in both WT and MHC-FATP myocytes to the same length, suggesting that MHC-FATP myocytes are partially activated at rest. Direct measurements of intracellular Ca
2+
revealed that diastolic [Ca
2+
]
i
is unchanged in MHC-FATP myocytes and the rate of calcium removal is unexpectedly faster in MHC-FATP than WT myocytes. Moreover, diastolic sarcomere length in MHC-FATP and WT myocytes was unaffected by removal of extracellular Ca
2+
or by buffering of intracellular Ca
2+
with the Ca
2+
chelator BAPTA (100 μmol/L), indicating that elevated intracellular Ca
2+
does not underlie impaired diastolic function in MHC-FATP ventricular myocytes. Functional assessment of skinned myocytes, however, revealed that myofilament Ca
2+
sensitivity is markedly increased in MHC-FATP, compared with WT, ventricular cells. In addition, biochemical experiments demonstrated increased expression of the β-MHC isoform in MHC-FATP, compared with WT ventricles, which likely contributes to the slower relaxation rate observed in MHC-FATP myocytes. Collectively, these data demonstrate that derangements in lipid metabolism in MHC-FATP ventricles, which are similar to those observed in the diabetic heart, result in impaired diastolic function that primarily reflects changes in myofilament function, rather than altered Ca
2+
cycling.
Unique Hexosaminidase Reduces Metabolic Survival Signal and Sensitizes Cardiac Myocytes to Hypoxia/Reoxygenation Injury
Authors: Ngoh Gladys A. , Facundo Heberty T. , Hamid Tariq , Dillmann Wolfgang , Zachara Natasha E. , Jones Steven P.
Published: November 2008

Metabolic signaling through the posttranslational linkage of
N
-acetylglucosamine (
O
-GlcNAc) to cellular proteins represents a unique signaling paradigm operative during lethal cellular stress and a pathway that we and others have recently shown to exert cytoprotective effects in vitro and in vivo. Accordingly, the present work addresses the contribution of the hexosaminidase responsible for removing
O
-GlcNAc (ie,
O
-GlcNAcase) from proteins. We used pharmacological inhibition, viral overexpression, and RNA interference of
O
-GlcNAcase in isolated cardiac myocytes to establish its role during acute hypoxia/reoxygenation. Elevated
O
-GlcNAcase expression significantly reduced
O
-GlcNAc levels and augmented posthypoxic cell death. Conversely, short interfering RNA directed against, or pharmacological inhibition of,
O
-GlcNAcase significantly augmented
O
-GlcNAc levels and reduced posthypoxic cell death. On the mechanistic front, we evaluated posthypoxic mitochondrial membrane potential and found that repression of
O
-GlcNAcase activity improves, whereas augmentation impairs, mitochondrial membrane potential recovery. Similar beneficial effects on posthypoxic calcium overload were also evident. Such changes were evident without significant alteration in expression of the major putative components of the mitochondrial permeability transition pore (ie, voltage-dependent anion channel, adenine nucleotide translocase, cyclophilin D). The present results provide definitive evidence that
O
-GlcNAcase antagonizes posthypoxic cardiac myocyte survival. Moreover, such results support a renewed approach to the contribution of metabolism and metabolic signaling to the determination of cell fate.
The Importance of Cerebral Aneurysms in Childhood Hemorrhagic Stroke
Authors: Jordan Lori C. , Johnston S. Claiborne , Wu Yvonne W. , Sidney Stephen , Fullerton Heather J.
Published: November 2008

Background and Purpose—

Prior population-based studies of pediatric hemorrhagic stroke (HS) had too few incident cases to assess predictors of cerebral aneurysms, a HS etiology that requires urgent intervention.

Methods—

We performed a retrospective cohort study of HS (intracerebral, subarachnoid [SAH], and intraventricular hemorrhage) using the population of all children <20 years of age enrolled in a large Northern Californian healthcare plan (January 1993 to December 2003). Cases were identified through electronic searches and confirmed through independent chart review by 2 neurologists with adjudication by a third; traumatic hemorrhages were excluded. Logistic regression was used to examine potential predictors of underlying aneurysm.

Results—

Within a cohort of 2.3 million children followed for a mean of 3.5 years, we identified 116 cases of spontaneous HS (overall incidence, 1.4 per 100000 person-years). Cerebral aneurysms were identified in 15 (13%) of HS cases. Among 21 children with pure SAH, 57% were found to have an underlying aneurysm compared with only 2% of 58 children with pure intracerebral hemorrhage and 5% of 37 children with a mixed pattern of hemorrhage (intracerebral hemorrhage and SAH). Independent predictors of an underlying aneurysm included pure SAH (OR, 76; 95% CI, 9 to 657;
P
<0.001) and late adolescent age (15 to 19 years versus younger age groups; OR, 6.4; 95% CI, 1.0 to 40;
P
=0.047).

Conclusions—

Cerebral aneurysms cause the majority of spontaneous SAH in children and account for more than 10% of childhood HS overall. Children, and particularly teenagers, presenting with spontaneous SAH should be promptly evaluated with cerebrovascular imaging.
Exaggeration of Focal Cerebral Ischemia in Transgenic Mice Carrying Human Renin and Human Angiotensinogen Genes
Authors: Inaba Shinji , Iwai Masaru , Tomono Yumiko , Senba Izumi , Furuno Megumi , Kanno Harumi , Okayama Hideki , Mogi Masaki , Higaki Jitsuo , Horiuchi Masatsugu
Published: November 2008

Background and Purpose—

We examined the possibility that activation of the human brain renin–angiotensin system is involved in enhancement of ischemic brain damage using chimeric transgenic mice with human renin (hRN) and human angiotensinogen (hANG) genes.

Methods—

Chimeric (hRN/hANG-Tg) mice were generated by mating of hRN and hANG transgenic mice. Permanent occlusion of the middle cerebral artery (MCA) by an intraluminal filament technique induced focal ischemic brain lesions.

Results—

hRN/hANG-Tg mice showed higher angiotensin II levels in the plasma and brain. The ischemic brain area at 24 hours after MCA occlusion was significantly enlarged in hRN/hANG-Tg mice with an enhanced neurological deficit compared to that in wild-type, hRN-Tg and hANG-Tg mice. The reduction of cerebral blood flow in the periphery region of the MCA territory after MCA occlusion was markedly exaggerated in hRN/hANG-Tg mice. Superoxide anion production in the brain and arteries was also increased significantly in hRN/hANG-Tg mice even before MCA occlusion and was further enhanced after MCA occlusion. Treatment with an AT
1
receptor blocker, valsartan (3.0 mg/kg per day), for 2 weeks significantly reduced the ischemic brain area and improved the neurological deficit after MCA occlusion in hRN/hANG-Tg mice, similar to those in wild-type, hRN-Tg, and hANG-Tg mice, with restoration of cerebral blood flow in the peripheral region and decreases in superoxide anion production and blood pressure.

Conclusions—

These results indicate that activation of the human renin–angiotensin system exaggerates ischemic brain damage mainly through stimulation of the AT
1
receptor and marked reduction of cerebral blood flow and enhanced oxidative stress.
Gene Variants Associated With Ischemic Stroke
Authors: Luke May M. , O'Meara Ellen S. , Rowland Charles M. , Shiffman Dov , Bare Lance A. , Arellano Andre R. , Longstreth W.T. , Lumley Thomas , Rice Kenneth , Tracy Russell P. , Devlin James J. , Psaty Bruce M.
Published: November 2008

Background and Purpose—

The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke.

Methods—

Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS).

Results—

In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in
HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1
, and
BAT2
) were nominally associated with increased risk of stroke (one-sided
P
<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in
KRT4, LY6G5B, EDG1, DMXL2
, and
ABCG2
) were nominally associated with stroke (one-sided
P
<0.05, false discovery rate=0.55). The Val12Met SNP in
ABCG2
was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS.

Conclusions—

The Val12Met SNP in
ABCG2
(encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.
The Essen Stroke Risk Score Predicts Recurrent Cardiovascular Events
Authors: Weimar Christian , Diener Hans-Christoph , Alberts Mark J. , Steg P. Gabriel , Bhatt Deepak L. , Wilson Peter W.F. , Mas Jean-Louis , Röther Joachim
Published: November 2008

Background and Purpose—

Predictive scores are important tools for stratifying patients based on the risk of future (cerebro)vascular events and for selecting potential prevention therapy. Recently, the Essen Stroke Risk Score (ESRS) was derived from cerebrovascular patients in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. We aimed to validate the ESRS in a large cohort of outpatients with previous transient ischemic attack or stroke from the REduction of Atherothrombosis for Continued Health (REACH) Registry.

Methods—

We included 15605 outpatients with a qualifying stroke or transient ischemic attack and with clinical follow-up at 1 year. Patients with atrial fibrillation were excluded. We stratified 1-year cumulative rates for fatal and nonfatal stroke as well as combined major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) by the individually calculated stroke risk profile according to the ESRS and compared it with the 1-year event rates in the CAPRIE data subset of 6431 cerebrovascular patients.

Results—

The 1-year rate for recurrent stroke (or combined cardiovascular events) in the stable outpatient population of REACH increased steadily and significantly from 1.82 (2.41) in patients with ESRS 0 to 6.84 (11.48) for ESRS >6. The overall as well as stratified risk of recurrent stroke and cardiovascular events was lower than for cerebrovascular patients in CAPRIE.

Conclusions—

In outpatients with previous stroke or transient ischemic attack, the ESRS accurately stratifies the risk of recurrent stroke or major vascular events. Patients with a high ESRS should be candidates for intensified secondary prevention strategies.
Leptin Is Induced in the Ischemic Cerebral Cortex and Exerts Neuroprotection Through NF-κB/c-Rel–Dependent Transcription
Authors: Valerio Alessandra , Dossena Marta , Bertolotti Paola , Boroni Flora , Sarnico Ilenia , Faraco Giuseppe , Chiarugi Alberto , Frontini Andrea , Giordano Antonio , Liou Hsiou-Chi , Grazia De Simoni Maria , Spano PierFranco , Carruba Michele O. , Pizzi Marina , Nisoli Enzo
Published: November 2008

Background and Purpose—

Leptin is an adipose hormone endowed with angiopoietic, neurotrophic, and neuroprotective properties. We tested the hypothesis that leptin might act as an endogenous mediator of recovery after ischemic stroke and investigated whether nuclear transcription factors κB activation is involved in leptin-mediated neuroprotection.

Methods—

The antiapoptotic effects of leptin were evaluated in cultured mouse cortical neurons from wild-type or NF-κB/c-Rel
−/−
mice exposed to oxygen–glucose deprivation. Wild-type, c-Rel
−/−
and leptin-deficient
ob/ob
mice were subjected to permanent middle cerebral artery occlusion. Leptin production was measured in brains from wild-type mice with quantitative reverse transcriptase–polymerase chain reaction and immunostaining. Mice received a leptin bolus (20 μg/g) intraperitoneally at the onset of ischemia.

Results—

Leptin treatment activated the nuclear translocation of nuclear transcription factors κB dimers containing the c-Rel subunit, induced the expression of the antiapoptotic c-Rel target gene Bcl-xL in both control and oxygen–glucose deprivation conditions, and counteracted the oxygen–glucose deprivation-mediated apoptotic death of cultured cortical neurons. Leptin-mediated Bcl-xL induction and neuroprotection against oxygen–glucose deprivation were hampered in cortical neurons from c-Rel
−/−
mice. Leptin mRNA was induced and the protein was detectable in microglia/macrophage cells from the ischemic penumbra of wild-type mice subjected to permanent middle cerebral artery occlusion. O
b/ob
mice were more susceptible than wild-type mice to the permanent middle cerebral artery occlusion injury. Leptin injection significantly reduced the permanent middle cerebral artery occlusion-mediated cortical damage in wild-type and
ob/ob
mice, but not in c-Rel
−/−
mice.

Conclusions—

Leptin acts as an endogenous mediator of neuroprotection during cerebral ischemia. Exogenous leptin administration protects against ischemic neuronal injury in vitro and in vivo in a c-Rel-dependent manner.