Metabolism

Following the intravenous administration of thromboxane (TX) i~, the stable hydration product of TXA z, to human and nonhuman prim_~.t~,~ file mo~¢ abundant urinary metabolites are 2,3-dinor-TXl~ and ll-dehydro-TXl~. However, it is not known w£,.+~~' ,,+-.-::,~:~,::,~:. :+ ~,:,,~ ~,'-~+on of TXlg z to its enzymatic metabolites is an accurate representation of TXA z metabolism. Thus, we have compared the metabolic disposition of synthetic TXA z and TXB z via the fl-oxidation and ll-OH-dehydrogenase pathways in vivo in the monkey. TXA, or ~ (20 ng/kg) was intravenously administered to four cynomolgus monkeys pretreated with aspirin in order to suppress endogenous TXA z production. Urinary TXI~, 2,3-diuor-TXl~ and ll-dehydro-TXl~ were measm'ed before, during and up to 24 h after thromboxane administration by means of reversed-phase high-pedormance liquid chromatography radioimmunoassay. Aspirin treatment suppressed urinary 2,3-dinor-TXl~ and ll-dehydro-TXl~ by approx. 75%. A similar fractional conversion of TXA, and ~ into 2,3-dinor-TXl~ and ll-dehydro-TXl~ was found. These results suggest that TXA 2 is hydrolyzod to ~ prior to enzymatic degradation and that metabolites of the latter represent reliable indices of TXA 2 biosynthesis. Due to the variability in the conversion of thromboxanes into 2,3-dinor-TXi~ and II-dehydro-TXBz, the measurement of both metabolites seems to represent a more reliable index of acute changes in TXA, production.

There are two ways how the emergence of the Biosphere as a single living being could be understood. One, that it is the latest stage of the evolution of life on Earth that began some 4 billion years ago, from smallest and simplest organisms to the larger and more complex. Another would be, that entire development of life was just an embryonic growth of the largest the most complex living being on Earth. Since the Biosphere is and will be quite a complex organism, it is almost certain that will acquire some kind of intelligence as a single being (entity). Although it will be dominated by the human component of its being, it will include some other living beings as well. However, how this intelligence will manifest itself is hard to anticipate or imagine at this point. In addition to possible self-awareness, it might be able to acquire some other properties unknown even unimaginable to us.

PHOTOSYNTHESIS Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that can later be released to fuel the organisms' activities (energy transformation). This chemical energy is stored in carbohydrate molecules, such as sugars, which are synthesized from carbon dioxide and water – hence the name photosynthesis, from the Greek φῶς, phōs, "light", and σύνθεσις, synthesis, "putting together". In most cases, oxygen is also released as a waste product. Most plants, most algae, and cyanobacteria perform photosynthesis; such organisms are called photoautotrophs. Photosynthesis is largely responsible for producing and maintaining the oxygen content of the Earth's atmosphere, and supplies all of the organic compounds and most of the energy necessary for life on Earth. Although photosynthesis is performed differently by different species, the process always begins when energy from light is absorbed by proteins called reaction centres that contain green chlorophyll pigments. In plants, these proteins are held inside organelles called chloroplasts, which are most abundant in leaf cells, while in bacteria they are embedded in the plasma membrane. In these light-dependent reactions, some energy is used to strip electrons from suitable substances, such as water, producing oxygen gas. The hydrogen freed by the splitting of water is used in the creation of two further compounds that serve as short-term stores of energy, enabling its transfer to drive other reactions: these compounds are reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine triphosphate (ATP), the "energy currency" of cells. In plants, algae and cyanobacteria, long-term energy storage in the form of sugars is produced by a subsequent sequence of light-independent reactions called the Calvin cycle; some bacteria use different mechanisms, such as the reverse Krebs cycle, to achieve the same end. In the Calvin cycle, atmospheric carbon dioxide is incorporated into already existing organic carbon compounds, such as ribulose bisphosphate (RuBP). Using the ATP and NADPH produced by the light-dependent reactions, the resulting compounds are then reduced and removed to form further carbohydrates, such as glucose.

To present athletic trainers with recommendations for safe weight loss and weight maintenance practices for athletes and active clients and to provide athletes, clients, coaches, and parents with safe guidelines that will allow athletes and clients to achieve and maintain weight and body composition goals.

Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m(2)) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively wi...

Omega 3 fatty acids are issued from linolenic acid (18:3ω3). Nutritional interest about ω3 fatty acids has begun since the epidemiological studies of Dyerberg et al. have shown a relationship between consumption of marine fats and reduction of cardiovascular diseases. Long-chain ω3 fatty acids, mainly eicosapentaenoic (20:5ω3 or EPA) and docosahexaenoic (22:6ω3 or DHA) acids, are considered to be the main bioactive components in marine sources. Other studies have confirmed that consumption of fish ou EPA\\DHA supplements may reduce mortality in patients who have suffered from myocardial infarction. Beneficial effects of ω3 fatty acids are also recognized in inflammatory disorders. The main mechanism involved for those effects is assumed to be the interference between long-chain ω3 fatty acids and the arachidonic acid (AA) metabolism in blood and vascular cells. In those cells, AA may be released from membrane phospholipids by phospholipase A 2 and subsequently oxygenated into eicosanoids (overall called AA cascade). According to the cell, oxygenated products from AA include thromboxane (platelets), prostacyclin (endothelial cells) and leukotrienes (leukocytes). EPA and DHA can interfere with AA cascade by several ways to reduce the vascular risk. However, high intake of such fatty acids may increase lipid peroxidation and have deleterious effects, in particular in subjects suffering from oxidative stress, whereas law may exert "antioxidant" activity. We conclude that a moderate consumption of longchain ω3 fatty acids can protect against cardiovascular dysfunction.

Variants in the TCF7L2 gene have been associated with type 2 diabetes mellitus (T2DM), but the causal variant(s) is still unknown. We studied the TCF7L2 messenger RNA (mRNA) expression in paired samples of visceral and subcutaneous adipose tissue from 49 subjects using quantitative real-time polymerase chain reaction and its relation to obesity and T2DM. All subjects were genotyped for the previously described TCF7L2 diabetes risk variants. Independent of age, sex, obesity, and diabetes status, we found N3-fold higher TCF7L2 mRNA expression in subcutaneous compared with visceral adipose tissue. There was no correlation between visceral and subcutaneous TCF7L2 expression. No differences in adipose tissue TCF7L2 mRNA expression levels were found between diabetic and nondiabetic subjects, or between lean and obese subjects (all Ps N .05). In addition, there was no association between TCF7L2 genetic variants and mRNA expression. Based on our data, TCF7L2 mRNA expression is fat-depot specific but does not seem to provide the mechanistic link explaining genetic association with T2DM.

A randomized clinical intervention trial to determine effects of lactation and 1 g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7, placebo [PI = 8) consuming 13-2.4 g of Ca/day from diet + prenatal supplement. Study periods were baseline, 5 2 weeks postpartum; lactation, 3 months lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD) corrected for body weight was determined by dual-energy X-ray absorptiometry (DXA). Indicators of calcium metabolism, bone turnover, and lactation were measured: calcium metabolism, parathyroid hormone (PTH), 25-hydroxyvitamin D (25 [OH] D), 1,25-dihydroxyvitamin D (1,25 [OH],D); bone turnover, formation, procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase (B-ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation, prolactin (PRL). Mean BMD changes differed by site: baseline to lactation-43% (P) (p < 0.04) and-63% (Ca) (p < 0.01) at the lumbar spine (L2-U) and 5.7% gains of the ultradistal (UD) radius (Ca) (p < 0.04); lactation to postweaning,-6% to-11% at all sites of the radius and ulna (Ca, P) (p < 0.04) +3% at L2-U (Ca) (p < 0.03); baseline to postweaning, (UD) radius-5.2% (P) (p < 0.03), UD radius + ulna-6% to-8% (Ca, P) (p < 0.04) but no significant loss of L2-L4 or total body. Bone turnover markers were higher at lactation than postweaning: PICP (+34%,p < 0.001), osteocalcin (+25%,p < 0.01), TRAP (+ll%,p < 0.005) as was PRL (+81%,p < 0.001). Indicators of calcium metabolism were higher postweaning than lactation for PTH (+4wo,p < 0.01) and 25(OH)D (+45%, p < 0.02) but not for 1,25(OH),D. There were no differences between P or Ca for indices of calcium metabolism, bone turnover, or PRL. An increase in markers of bone turnover and a loss of BMD of the spine during lactation appears to be part of the physiological changes of lactation and not preventable by increasing calcium intake above the recommended dietary allowance (RDA). A return of BMD toward baseline of the spine but not the arm, was associated with an increase in PTH without an increase in 1,25(OH),D postweaning. Loss of estrogen during lactation and a return postweaning may play an important role.

Values for body surface area (BSA) are commonly used in medicine, particularly to calculate doses of chemotherapeutic agents and index cardiac output. Various BSA formulas have been developed over the years. The DuBois and DuBois (Arch Intern Med 1916;17:863-71) BSA equation is the most widely used, although derived from only 9 subjects. More recently, Mosteller (N Engl J Med 1987;317:1098) produced a simple formula, [weight (kg) Â height (cm)/3600] 1/2 , which could be easily remembered and evaluated on a pocket calculator, but validation data in adults are rare. The purpose of the present study was to examine the BSA based on Mosteller's formula in normal-weight (body mass index [BMI], 20-24.9 kg/m 2), overweight (BMI, 25-29.9 kg/m 2), and obese (BMI, z 30 kg/m 2) adults (N 18 years old) in comparison with other empirically derived formulas (DuBois and DuBois, Boyd [The growth of the surface area of the human body.

Motivation: To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein-protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). Results: To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the Micro-Array Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein-protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The * To whom correspondence should be addressed. † The authors wish it to be known that, in their opinion, these two authors should be regarded as joint First Authors. open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. Availability: A universal modeling language depiction of the entire SysBio-OM is available at http://cebs.niehs.nih.gov/ SysBioOM/. The Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. The database and interface are being built to implement the model and will be available for public use at http://cebs.niehs.nih.gov.

Traumatic brain injury (TBI) remains a major cause of morbidity and mortality, particularly in young people. Despite encouraging animal studies, human trials assessing the use of pharmacological agents after TBI have all failed to show efficacy. Current management strategies are therefore directed towards providing an optimal physiological environment in order to minimize secondary insults and maximize the body's own regenerative processes. Modern neurocritical care management utilizes a host of monitoring techniques to identify or predict the occurrence of secondary insults and guide subsequent therapeutic interventions in an attempt to minimize the resulting secondary injury. Recent data suggest that the use of protocolized management strategies, informed by multimodality monitoring, can improve patient outcome after TBI. Developments in multimodality monitoring have allowed a movement away from rigid physiological target setting towards an individually tailored, patient-specific, approach. The wealth of monitoring information available provides a challenge in terms of data integration and accessibility and modern software applications may aid this process. 2007; 99: 61-7

In recent years, the adipose tissue has emerged as an important endocrine organ. It is now recognized that besides storing energy the adipocytes also secrete several bioactive peptides, collectively called adipocytokines. Among these adipocytokines, leptin, the product of the ob gene, has been extensively investigated over the last decade. Skeletal muscle and adipose tissue, two major tissues involved in the regulation of glucose and fatty acids metabolism, have been consistently demonstrated to be directly affected by leptin. By binding to its receptors located in skeletal muscle and fat cells, leptin promotes energy dissipation and prevents fatty acid accumulation and 'lipotoxicity' in these tissues. On the other hand, under conditions of peripheral leptin resistance, such as observed in obese humans, the activation of pathways involved in fatty acid oxidation may be impaired. This leads to intracellular accumulation of lipid intermediates and causes insulin resistance. This review examines the metabolic pathways that are directly activated by leptin and how it regulates glucose and fatty acids metabolism in skeletal muscle and fat tissue. Furthermore, the impact of peripheral leptin resistance in these tissues leading to dysfunctional metabolic adaptations is also discussed.

Eighteen poor sleepers and 18 good sleepers of mean age 52 yr, selected on the basis of their stated opinions about their sleep, were studied as pairs matched for sex, age, height and weight, on five consecutive nights and two consecutive days. Using EEG measures, the poor sleepers woke more often in the early hours of sleep and achieved half an hour less sleep. They had higher body temperatures by day and night and were more anxious. They tended to have higher urinary cortisol and adrenaline excretion. The groups did not differ in reaction time nor in excretion of urinary 3-methylhistidine. The poor sleepers overestimated their sleep latency and both groups underestimated their total sleep, the poor sleepers being significantly more inaccurate. It is concluded that those who complain of poor sleep have also metabolic differences from good sleepers.

Herbaceous temperate plants are capable of developing freezing tolerance when they are exposed to low nonfreezing temperatures. Acquired freezing tolerance involves extensive reprogramming of gene expression and metabolism. Recent full-genome transcript profiling studies, in combination with mutational and transgenic plant analyses, have provided a snapshot of the complex transcriptional network that operates under cold stress. The changes in expression of hundreds of genes in response to cold temperatures are followed by increases in the levels of hundreds of metabolites, some of which are known to have protective effects against the damaging effects of cold stress. Genetic analysis has revealed important roles for cellular metabolic signals, and for RNA splicing, export and secondary structure unwinding, in regulating cold-responsive gene expression and chilling and freezing tolerance. These results along with many of the others summarized here further our understanding of the basic mechanisms that plants have evolved to survive freezing temperatures. In addition, the findings have potential practical applications, as freezing temperatures are a major factor limiting the geographical locations suitable for *Corresponding author growing crop and horticultural plants and periodically account for significant losses in plant productivity. Although, great progress has been made in the field but lacunae still remain since it appears that the cold resistance is more complex than perceived and involves more than one pathway. Cold stress is a major environmental factor that limits the agricultural productivity of plants. Low temperature has a huge impact on the survival and geographical distribution of plants. Cold stress often affects plant growth and crop productivity, which causes significant crop losses (Xin and Browse, 2000). Plants differ in their tolerance to chilling (0-15ºC) and freezing (< 0ºC) temperatures. Plants from temperate regions are chilling tolerant, although most are not very tolerant to freezing but can increase their freezing tolerance by being exposed to chilling, non freezing temperatures, a process known as cold acclimation (Levitt, 1980), which is associated with biochemical and physiological changes (Shinozaki and Yamaguchi-Shinozaki, 1996; Thomashow, 1998; Gilmour et al. 2000). By contrast, plants of tropical and subtropical origins, including many crops such as rice, maize and tomato are

Mesterolone (1␣-methyl-5␣-androstan-17␤-ol-3-one) is a synthetic anabolic androgenic steroid (AAS) with reported abuses in human sports. As for other AAS, mesterolone is also a potential doping agent in equine sports. Metabolic studies on mesterolone have been reported for humans, whereas little is known about its metabolic fate in horses. This paper describes the studies of both the in vitro and in vivo metabolism of mesterolone in racehorses with an objective to identify the most appropriate target metabolites for detecting mesterolone administration.

Sulfation of the carcinogen N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and structurally related hydroxamic acids by rat and human sulfotransferases was studied. There was a clear sex and age difference in the sulfation of N-OH-AAF and the other hydroxamic acids by rat liver cytosols: adult male rats had the highest sulfation activity. Experiments with purified aryl sulfotransferase IV (AST IV) indicated that the high expression of this enzyme in male rat liver may be responsible for these differences. No such sex or age difference was found for the sulfation of aromatic hydroxylamines. In cytosols of adult human livers, sulfation activity towards aromatic hydroxamic acids and hydroxylamines was clearly present, but activities were much lower than in rat liver cytosols. Sulfation activity towards these compounds was also found in fetal and neonatal liver and adrenals. These compounds probably are sulfated by several different sulfotransferases in humans

Somatostatin (SRIF) receptors (ssts) comprise a family of heptahelical membrane proteins encoded by five related genes that map to separate chromosomes and which, with the exception of SStl, are intronless. The sstsl.4 display weak selectivity for SRIF-14 binding, whereas ssts is SRIF-28-selective. Based on structural similarity and reactivity for octapeptide and hexapeptide sst analogs, ssts2,3 and sst5 belong to a similar sst subclass; ssts14 react poorly with these analogs and belong to a separate subclass. All five ssts are functionally coupled to inhibition of adenylyl cyclase via pertussis toxin-sensitive guanosine triphosphate (GTP)-binding proteins, mRNA for sstsl.s is widely expressed in brain and peripheral organs and displays an overlapping but characteristic pattern that is subtype.selective and tissue-and species-specific. All pituitary cell subsets express sst2 and ssts, with ssts being more abundant. Individual pituitary cells coexpress multiple sst subtypes. The binding pocket for SRIF-14 ligand lies deep within the membrane in transmembrane domains (TMDs) 3 to 7. Except for extracellular loop 2, it does not involve the other exofacial structures. Human (h)sstzA and hssts undergo agonist-mediated desensitization, associated with receptor internalization. The C-tail segment of hssts displays positive molecular internalization signals. The ssts inhibit the growth of tumor cells directly, through blockade of mitogenic signaling leading to growth arrest and through induction of apoptosis. This process is associated with translocation of phosphotyrosine phosphatase (PTP) 1C from the cytosol to the membrane.

In many instances, children and older adults show similar difficulties in reward-based learning and outcome monitoring. These impairments are most pronounced in situations in which reward is uncertain (e.g., probabilistic reward schedules) and if outcome information is ambiguous (e.g., the relative value of outcomes has to be learned). Furthermore, whereas children show a greater sensitivity to external outcome information, older adults focus less on a rapid differentiation of rewarding outcomes. In this article, we review evidence for the idea that these phenomenologically similar impairments in learning and outcome monitoring in children and older adults can be attributed to deficits in different underlying neurophysiological mechanisms. We propose that in older adults learning impairments are the result of reduced dopaminergic projections to the ventromedial prefrontal cortex, which lead to less differentiated representations of reward value. In contrast, in children, impairments in learning can be primarily attributed to deficits in executive control, which may be due to a protracted development of the dorsal medial and lateral prefrontal cortices. We think that this framework maps well onto recent neurophysiological models of reward processing and is plausible from a broader developmental perspective.

17␤-Nandrolone (17␤-NT) is one of the most recurrent forbidden anabolic steroid used in meat producing animals breeding. Because efficient control must both take into account metabolic patterns and associated kinetics of elimination, the metabolism of 17␤-NT in bovines has already been investigated and is well documented, but only focussing on its main metabolites (i.e. 17␣-nandrolone, 19-noretiocholanolone and 19-norandrostenedione). The goal of the present study was to enlarge this panel of 17␤-NT metabolites, especially through the urinary estranediols fraction in order to perform a more global steroid profiling upon 17␤-nortestosterone laureate ester administration in calves. A GC-MS/MS method has been developed to monitor and quantify 5 estranediols isomers including 5␣-estrane-3␤,17␤-diol (abb), 5␤-estrane-3␣,17␤-diol (bab), 5␣-estrane-3␤,17␣-diol (aba), 5␣-estrane-3␣,17␤-diol (aab) and 5␤estrane-3␣,17␣-diol (baa). Their urinary elimination kinetics have been established allowing detection of 4 estranediols up to several days after administration. All animals demonstrated homogeneous patterns of elimination both from a qualitative (metabolite profile) and quantitative point of view (elimination kinetics in urine). 5␣-Estrane-3␤,17␣-diol (aba) was found as the major metabolite with concentrations up to 100 g L −1 .

From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (PFJ, AGB, IHR, JS); the NHLBI Family Heart Study, University of Utah Cardiovascular Genetics Research Clinic, Salt Lake City (RRW); the NHLBI Family Heart Study, ...

Vitamins are organic compounds that play a vital role in the control of metabolic processes. The D complex is considered a nutrient with a hormonal action and has an important participation in the constant maintenance of serum and extracellular calcium levels. The present study aims to analyze the results of 105.588 vitamin D (25(OH)D) measurements obtained from a database from a clinical analysis laboratory in Brazil, between the years of 2011 and 2013. The values of 25(OH)D were correlated with age, gender, and values of PTH. The results show a high prevalence of values of 25(OH)D considered inadequate, characterizing 76% of the studied population. It was observed that 26,5% of the individuals had deficiency and 49,5% had insufficiency of vitamin D. It was also shown that there was a negative correlation between 25(OH)D and PTH levels. In conclusion, this study is in accordance with others that show a high prevalence of vitamin D deficiency in different populations and alerts us for the importance of these measurements and analysis in clinical practice and as a base for diagnosis and treatment of hypovitaminosis.

Resistance to fenitrothion and enzyme activities associated with the toxicity and metabolism of organophosphorus insecticides were measured in three genetically unique Daphnia magna clones collected from rice fields of Delta del Ebro (NE Spain) during the growing season and a lab sensitive clone. The studied clones showed up to sixfold differences in resistance to fenitrothion. The lack of correlation between in vitro sensitivity of acetylcholinesterase (AChE) to fenitrooxon and resistance to fenitrothion indicated that insensitivity of AChE to the most active oxon metabolite was not involved in the observed differences in resistance. Inhibition of mixed-function oxidases (MFOs) by piperonyl butoxide (PBO) increased the tolerance to fenitrothion by almost 20-fold in all clones without altering their relative ranking of resistance. Conversely, when exposed to fenitrooxon, the studied clones showed similar levels of tolerance, thus indicating that clonal differences in the conversion of fenitrothion to fenitrooxon by MFOs were involved in the observed resistance patterns. Despite that resistant clones showed over 1.5 higher activities of carboxilesterase (CbE) than sensitive ones, toxicity tests with 2-(O-cresyl)-4H-1,3,2-benzodioxaphosphorin-2 oxide, which is a specific inhibitor of these enzymes, evidenced that this system only contributed marginally to the observed clonal differences in tolerance. Glutathione-S-transferases activity (GST) varied across clones but not under exposure to fenitrothion, and was only related with tolerance levels in the field clones. In summary, our results indicate that MFO mediated differences on the bio-activation of the phosphorotionate OP pesticide to its active oxon metabolite contributed mostly in explaining the observed moderate levels of resistance, whereas the activities of CbE and GST had only a marginal role.

Acute exposure to moderate (552Torr, 73.6kPa) and high (428Torr, 57.1 kPa) altitude resulted in a decrease in the thermosensitivity of arm, chest and thigh sweating during light and moderate exercise. This effect was not accompanied by any change in the esophageal temperature threshold for sweating onset at any of the three sites. 2. Whole body wettedness was decreased an average of 23% at high altitude during light (40°/. ~O 2 peak) and moderate (60% ~O2 peak) exercise. There was no change in mean weighted skin temperature at either moderate or high altitude.

Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

Ž. Ž. Ž. Ethanol 0.5 grkg i.p. 15 min prior to sacrifice increased homovanillic acid HVA levels in the left medial prefrontal cortex mPFC Ž. Ž. of left-turning rats and in the right mPFC of right-turning rats. In the nucleus accumbens NAS , ethanol decreased dopamine DA , Ž. 3,4-dihydroxyphenylacetic acid DOPAC , and HVA levels in rats that exhibited low levels of locomotor activity but not in rats that exhibited high levels of locomotor activity. This laboratory has previously shown that rats exhibiting differences in turning and locomotor activity behavior display different preferences for ethanol. The present results suggest that ethanol-induced differences in mPFC and NAS DA activity may be related to individual differences in the susceptibility to abuse ethanol.

Platelet activation is fundamentally involved in the initiation and development of atherosclerotic disease. It orchestrates
the triad of inflammation, atherosclerosis and thrombosis. Thienopyrindines are one of the most commonly prescribed
drugs for secondary prevention of cardiovascular diseases. Their mode of action is through irreversible inhibition of P2Y12
receptors on platelets and thereby antagonizing the effect of adenosine diphosphate (ADP) resulting in potent anti-platelet
effects. There are, however, emerging data over last decade, which indirectly support ADP-independent effects of thienopyridine
drugs with multiple beneficial modes of action in cardiovascular disease prevention. In this review, we focus on
the potential pleiotropic effects of thienopyridines.

Objective-Low salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects.

A multitude of endocrine mechanisms are involved in coping with challenges. Front-line hormones to overcome stressful situations are glucocorticoids (GCs) and catecholamines (CAs). These hormones are usually determined in plasma samples as parameters of adrenal activity and thus of disturbance. GCs (and CAs) are extensively metabolized and excreted afterwards. Therefore, the concentration of GCs (or their metabolites) can be measured in various body fluids or excreta. Above all, fecal samples offer the advantages of easy collection and a feedback-free sampling procedure. However, large differences exist among species regarding the route and time course of excretion, as well as the types of metabolites formed. Based on information gained from radiometabolism studies (reviewed in this paper), we recently developed and successfully validated different enzyme immunoassays that enable the noninvasive measurement of groups of cortisol or corticosterone metabolites in animal feces. The determination of these metabolites in fecal samples can be used as a powerful tool to monitor GC production in various species of domestic, wildlife, and laboratory animals.

Much remains to be clarified in the apparently protective effect of moderate alcohol use against coronary heart disease risk. Insulin levels are positively associated with coronary heart disease risk, so recent reports of decreased insulin sensitivity among nondrinkers and lower fasting insulin levels with increasing alcohol intake suggest the possibility that insulin may play a role. Between 1987 and 1991, the authors examined fasting insulin concentrations and the empiric fasting insulin resistance index in relation to reported alcohol intake (mean, 15.3 g/day; standard deviation, 19.6; range, 0-120.6) and potential confounders. The latter included age, obesity, fat distribution, smoking, energy, saturated fat intake, antihypertensive medication, and physical activity. Participants in this cross-sectional analysis were 938 nondiabetic men from the Boston, Massachusetts, area who were part of the Normative Aging Study. Unadjusted fasting insulin levels were significantly different (p = 0.008) between categories of alcohol intake, as were fasting insulin resistance index values (p = 0.01). After adjustment for potential confounders, analysis revealed that subjects consuming moderate amounts of alcohol had the lowest fasting insulin and fasting insulin resistance index values. Compared with values from moderate drinkers, fasting insulin resistance index values were higher in those subjects reporting no alcohol intake (p = 0.011), low intake (p = 0.004), and high intake (p = 0.04). A similar pattern was observed for fasting insulin values. Among this sample of nondiabetic men, moderate drinkers had the lowest levels of fasting insulin resistance index and fasting insulin, consistent with lower levels of insulin resistance and thus lower risk for cdronary heart disease. These findings suggest the possibility that the coronary heart disease-protective effects of moderate alcohol use are at least partially mediated by insulin. Am J Epidemiol 1997;145:909-16. alcohol drinking; coronary disease; insulin; risk factors Much remains to be clarified with regard to the protective effect of moderate habitual alcohol use against coronary heart disease risk (1). One plausible partial explanation (2) is that the lower coronary heart disease rates observed in subjects with low to moderate levels of alcohol intake are mediated by increased levels of high density lipoprotein cholesterol (3-5).

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitarygonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a neuroendocrine event. The complex organization of neurochemical events controlling the psychosocial, physiological, and anatomical events that constitute reversal of sexual identity includes monoamine neurotransmitters.

To determine the effects of anabolic steroids on serum lipid and apoprotein levels, 14 white male body builders who self-administered steroids for 2 to 3 months (steroid users) were studied; 10 agreed to screening while they were taking the drugs (ON treatment) and also at about 3 months following their suspension (OFF treatment).

All, but no tendency to precocious atherosclerosis is present. To elucidate this paradox, the structure of HDL, the potential of serum to promote cholesterol effiux from cultured cells, and the in vivo metabolism of HDL were examined in a 53-year-old Woman with a FED syndrome in association with a markedly decreased lecithin:cholesterol acyltransferase (LCAT) activity in HDL due to a mutation of the LCAT gene (Arglse -~ Cys). HDLs isolated by uitracentrifugation were small and enriched in unesterified cholesterol and phospholipids at the expense of cholesteryl esters and proteins, The apolipoprotein content showed an enrichment in apo E and apo AIV, whereas apo AI and apo All were dramatically reduced. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE} and immunoblotting using specific antibodies showed that the apo E was free or covalently bound to apo All. These particles analyzed by electron microscopy were small and round lipoproteins with a size similar to the smallest fraction of normal HDL3. The potential capacity of the serum to promote efflux from the cells was approximately 40% of control serum levels, but FED HDLs were as efficient as control HDLs in promoting cholesterol efflux from cells. To assess the metabolism of HDL apolipoproteins, in vivo apolipoprotein kinetic studies were performed using endogenous labeling techniques in the patient with FED and three control subjects. All subjects were administered D3-1abeled leucine by primed constant infusion for up to 10 hours. The fractional synthetic rates (FSRs) of apo AI and apo All in the patient were 0.674 and 0,594 per day, clearly higher than in controls, 0.210 +-0.053 and 0.148 +-0.014 per day for apo AI and apo All, respectively. Apo AI and apo All production rates in the patient with FED were normal, 11.32 and 2.62 mgJkg • d, respectively, as compared with those in normal subjects, 11.45 + 1.23 and 2.68 -+ 0.17 mg/kg • d. These data established that hypoalphalipoproteinemia in FED was caused by marked hypercatabolism of apo AI and apo All. This hypercatabolism could be the consequence of structural abnormalities due to the selective LCAT deficiency, in conclusion, two steps of reverse cholesterol transport, cholesterol efflux and apo-HDL metabolism, appeared particularly efficient. This efficiency could participate in the absence of premature atherosclerosis in FED patients as regards the low HDL level.

Objective: We aimed to examine the association between adolescents' sleep time and a cardiometabolic risk score. A second aim was to examine associations between sleep time and individual cardiometabolic risk factors. Methods: Adolescents (N = 699; ages, 12.5-17.5 years) participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study were examined. Sleep time was reported by a questionnaire. Physical activity (PA) was assessed by accelerometry (n = 497). Cardiometabolic risk factors measurements included insulin resistance, blood pressure, adiposity markers, cardiorespiratory fitness, and blood lipids. A cardiovascular disease risk score was computed. Associations were examined by a multilevel regression analysis (linear for individual risk factors and Poisson for the clustered risk score). Results: For school days no association was found between sleep time and cardiometabolic risk factors. At weekend days, the prevalence ratio (PR) of having a clustered risk score increased by 15% for each additional hour of sleep controlling for age, sex, and socioeconomic status (SES); however, the prevalence disappeared when adjusting for PA. Conclusions: In European adolescents sleep time is not associated with cardiometabolic risk factors when important confounders are considered. Future research about sleep cardiovascular risk factors should register other sleep dimensions (sleep patterns or disturbances) to provide a better insight in this scientific field.

The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.

Lampreys are a jawless vertebrate species belonging to an ancient vertebrate lineage that diverged from a common ancestor with humans ~500 million years ago. The sea lamprey (Petromyzon marinus) has a filter feeding ammocoete larval stage that metamorphoses into a parasitic adult, feeding both on teleost and elasmobranch fish. Lampreys are a valuable comparative model species for vertebrate immunity and physiology due to their unique phylogenetic position, unusual adaptive immune system, and physiological adaptions such as tolerance to salinity changes and urea. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which catalyses posttranslational deimination/citrullination in target proteins, enabling proteins to gain new functions (moonlighting). The identification of deiminated protein targets in species across phylogeny may provide novel insights into post-translational regulation of physiological and pathophysiological processes. Extracellular vesicles (EVs) are membrane vesicles released from cells that carry cargos of small molecules and proteins for cellular communication, involved in both normal and pathological processes. The current study identified deimination signatures in proteins of both total plasma and plasma-EVs in sea lamprey and furthermore reports the first characterisation of plasma-EVs in lamprey. EVs were poly-dispersed in the size range of 40-500 nm, similar to what is observed in other taxa, positive for CD63 and Flotillin-1. Plasma-EV morphology was confirmed by transmission electron microscopy. Assessment of deimination/citrullination signatures in lamprey plasma and plasma-EVs, revealed 72 deimination target proteins involved in immunity, metabolism and gene regulation in whole plasma, and 37 target proteins in EVs, whereof 24 were shared targets. Furthermore, the presence of deiminated histone H3, indicative of gene-regulatory mechanisms and also a marker of neutrophil extracellular trap formation (NETosis), was confirmed in lamprey plasma. Functional protein network analysis revealed some differences in KEGG and GO pathways of deiminated proteins in whole plasma compared with plasma-EVs. For example, while common STRING network clusters in plasma and plasma-EVs included Peptide chain elongation, Viral mRNA translation, Glycolysis and gluconeogenesis, STRING network clusters specific for EVs only included: Cellular response to heat stress, Muscle protein and striated muscle thin filament, Nucleosome, Protein processing in endoplasmic reticulum, Nucleosome and histone deacetylase complex. STRING network clusters specific for plasma were: Adipokinetic hormone receptor activity, Fibrinogen alpha/beta chain family, peptidase S1A, Glutathione synthesis and recycling-arginine, Fructose 1,6-bisphosphate metabolic process, Carbon metabolism and lactate dehydrogenase activity, Post-translational protein phosphorylation, Regulation of insulin-like growth factor transport and clotting cascade. Overall, for the EV citrullinome, five STRING network clusters, 10 KEGG pathways, 15 molecular GO pathways and 29 Reactome pathways were identified, compared with nine STRING network clusters, six KEGG pathways, two Molecular GO pathways and one Reactome pathway specific for whole plasma; while further pathways were shared. The reported findings indicate that major pathways relevant for immunity and metabolism are targets of deimination in lamprey plasma and plasma-EVs, with some differences, and may help elucidating roles for the conserved PAD enzyme family in regulation of immune and metabolic function throughout phylogeny.

toxicity has not been well elucidated. Understanding the Cellular Uptake of Trivalent Arsenite and Pentavalent Arsenate differential toxic mechanisms of As(III) and As(V) is critiin KB Cells Cultured in Phosphate-Free Medium. HUANG, R. N., cally important in assessing the risk from arsenic exposure. AND LEE, T. C. (1996). Toxicol. Appl. Pharmacol. 136, 243-249.

Bovine somatotropin (bST) results in increased milk yield and an unprecedented improvement in efficiency. Beginning in the 1930s to present day, investigations have examined animal-related factors such as nutrition, bioenergetics, metabolism, health and well being and consumer-related factors such as milk quality, manufacturing characteristics, and product safety. Overall, bST is a homeorhetic control involved in orchestrating many physiological processes. Direct effects involve adaptations in many tissues and the metabolism of all nutrient classes-carbohydrates, lipids, protein, and minerals. Mechanisms include alterations in key enzymes, intracellular signal transduction systems, and tissue response to homeostatic signals. Indirect effects involve the mammary gland and are thought to be mediated by the insulin-like growth factor (IGF) system. Specific changes include increased cellular rates of milk synthesis and enhanced maintenance of secretory cells. Indirect effects are modulated by environment and management factors, especially nutritional status. This modulation is a central component in allowing ST to play a key role in regulating nutrient utilization across a range of physiological situations. U.S. commercial use began in 1994, and adoption has been extensive. From a consumer perspective, bST was unique, and special interest groups loudly predicted dire consequences. However, introduction of bST had no impact on milk consumption, and milk labeled as recombinant bST-free occupies a minor niche market. From a producer perspective, commercial use verified scientific studies and enhanced net farm income. Overall, ST is a key homeorhetic control regulating nutrient partitioning, and the ST/IGF system plays a key role in animal performance and well being across a range of physiological situations.