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Kinds of Depot Terms modified by Depot Selected AbstractsPrevalence and serum protein values of strangles (Streptococcus equi) affected mules at Remount Depot, Sargodha (Pakistan)EQUINE VETERINARY EDUCATION, Issue 4 2010M. Ijaz Summary The prevalence of Streptococcus equi serovar equi (S.equi) in nasal discharge and pus samples from sub-mandibular lymph nodes in mules at the Remount Depot, Sargodha was examined and total serum proteins, serum albumin, serum globulin and fibrinogen measured. A total of 250 nasal swabs and pus samples were collected from mules and examined microbiologically: 99 (39.6%) were positive for S. equi. A higher occurrence of S. equi was recorded in foals as compared to adults. The concentrations of total serum protein, serum globulin and fibrinogen were significantly increased (P<0.05), while the concentration of serum albumin significantly decreased (P<0.05) in strangles-affected mules. It was concluded that increased total serum proteins, serum globulin and fibrinogen along with decreased serum albumin were important indicators of infection by S. equi in mules. [source] Treatment of an explosives plume in groundwater using an organic mulch biowallREMEDIATION, Issue 1 2009Farrukh Ahmad A field demonstration of a mulch permeable reactive barrier (PRB), or "biowall," as an in situ treatment technology for explosives in groundwater is summarized. Organic mulch consists of insoluble carbon biopolymers that are enzymatically hydrolyzed during decomposition to release aqueous total organic carbon (TOC). The released TOC is then available for microorganisms to use as an electron donor to transform electrophilic contaminants via reductive pathways. A 100-foot-long and 2-foot-thick mulch biowall was installed at the Pueblo Chemical Army Depot in Colorado to treat a shallow groundwater plume containing hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). To discourage groundwater flow bypassing around and under the biowall in this highly permeable formation, a hydraulic control was installed and the PRB was keyed into the bedrock. Technology performance was monitored using a monitoring well network to establish the development and extent of the downgradient treatment zone. Performance objectives of the field demonstration were: (1) greater than 90 percent removal of RDX across the PRB and the treatment zone; (2) an RDX concentration of less than 0.55 ,g/L in the treatment zone; and (3) cumulative toxic intermediate concentration (nitroso intermediates of RDX, MNX, DNX, and TNX) of less than 20 percent of the upgradient RDX concentration. All performance objectives were met within seven months after installation once the system reached a pseudo-steady state. By this point, a sustained reducing/treatment zone had been created downgradient of the mulch PRB that showed greater than 93 percent RDX removal, RDX concentrations less than 0.55 ,g/L, and no accumulation of toxic intermediates. The mulch biowall implemented during this demonstration was successful at meeting performance objectives while addressing the majority of potential concerns of the technology. © 2009 Wiley Periodicals, Inc. [source] Effect of Long-Term Testosterone Administration on the Endometrium of Female-to-Male (FtM) TranssexualsTHE JOURNAL OF SEXUAL MEDICINE, Issue 11 2009Anna Myriam Perrone MD ABSTRACT Introduction., Long term safety of testosterone (T) administration in women is still unknown. In particular few and discordant data exists on the effects of T on the endometrium. Aim., The aim of this study was to investigate the effects of long-term T treatment on endometrium histology and proliferation in female to male transsexual subjects (FtM). We compared these endometria with those of young women in the proliferative phase (PM) of the cycle and with those of post menopausal women (M). Method., Endometrial samples from 27 FtM treated with T (intramuscular injection of 100 mg Testoviron Depot /10 days for at least one year), 30 M undergoing vaginal hysterectomy, and 13 PM undergoing hysteroscopy for infertility problems were collected. Endometrial proliferation was evaluated on the basis of histopathology and expression of the proliferation marker Ki-67. Both M and PM women had not received any hormonal treatment for at least one year. Main Outcome Measure., Circulating total testosterone (TT), estradiol (E), progesterone (P), insulin and glucose levels were measured in FtM and PM subjects. Results., FtM had received T for 33.6 ± 21.3 months (mean ± SD). In FtM subjects, histological analysis found inactive endometrium similar to the atrophic menopausal endometrium. The expression of Ki-67 in the glands, stroma and glands and stroma together was significantly (p < 0.0005) lower in FtM than in PM women and was similar in the FtM and M groups. Small polyps were detected in 5 of the 27 FtM subjects. Conclusions., In conclusion our data suggest that exogenous T administration does not stimulate endometrial proliferation in FtM transsexuals and indeed may have atrophic effects. Perrone AM, Cerpolini S, Salfi NCM, Ceccarelli C, Badiali De Giorgi L, Formelli G, Casadio P, Ghi T, Pelusi G, Pelusi C, and Meriggiola MC. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med 2009;6:3193,3200. [source] Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker ratsDIABETES OBESITY & METABOLISM, Issue 6 2009D. Laurent Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source] An adipocentric view of signaling and intracellular traffickingDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2002Silvia Mora Abstract Adipocytes have traditionally been considered to be the primary site for whole body energy storage mainly in the form of triglycerides and fatty acids. This occurs through the ability of insulin to markedly stimulate both glucose uptake and lipogenesis. Conventional wisdom held that defects in fuel partitioning into adipocytes either because of increased adipose tissue mass and/or increased lipolysis and circulating free fatty acids resulted in dyslipidemia, obesity, insulin resistance and perhaps diabetes. However, it has become increasingly apparent that loss of adipose tissue (lipodystrophies) in both animal models and humans also leads to metabolic disorders that result in severe states of insulin resistance and potential diabetes. These apparently opposite functions can be resolved by the establishment of adipocytes not only as a fuel storage depot but also as a critical endocrine organ that secretes a variety of signaling molecules into the circulation. Although the molecular function of these adipocyte-derived signals are poorly understood, they play a central role in the maintenance of energy homeostasis by regulating insulin secretion, insulin action, glucose and lipid metabolism, energy balance, host defense and reproduction. The diversity of these secretory factors include enzymes (lipoprotein lipase (LPL) and adipsin), growth factors [vascular endothelial growth factor (VEGF)], cytokines (tumor necrosis factor-,, interleukin 6) and several other hormones involved in fatty acid and glucose metabolism (leptin, Acrp30, resistin and acylation stimulation protein). Despite the large number of molecules secreted by adipocytes, our understanding of the pathways and mechanisms controlling intracellular trafficking and exocytosis in adipocytes is poorly understood. In this article, we will review the current knowledge of the trafficking and secretion processes that take place in adipocytes, focusing our attention on two of the best characterized adipokine molecules (leptin and adiponectin) and on one of the most intensively studied regulated membrane proteins, the GLUT4 glucose transporter. Copyright © 2002 John Wiley & Sons, Ltd. [source] Insulin resistance in type 2 diabetes: role of fatty acids,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002Peter Arner Abstract Insulin resistance is one of the key factors responsible for hyperglycaemia in type 2 diabetes and can result in a number of metabolic abnormalities associated with cardiovascular disease (insulin resistance syndrome), even in the absence of overt diabetes. The mechanisms involved in the development of insulin resistance are multifactorial and are only partly understood, but increased availability of free fatty acids (FFAs) is of particular importance for the liver and skeletal muscle. The role of FFAs in type 2 diabetes is most evident in obese patients who have several abnormalities in FFA metabolism. Because of a mass effect, the release of FFAs from the total adipose tissue depot to the blood stream is increased and the high concentration of circulating FFAs impairs muscle uptake of glucose by competitive inhibition. In upper-body obesity, which predisposes individuals to type 2 diabetes, the rate of lipolysis is accelerated in visceral adipose tissue. This results in a selective increase in FFA mobilisation to the portal vein, which connects visceral fat to the liver. A high ,portal' FFA concentration has undesirable effects on the liver, resulting in dyslipidaemia, hyperinsulinaemia, hyperglycaemia and hepatic insulin resistance. Recently, a new class of antidiabetic agents, the thiazolidinediones (TZDs) or ,glitazones' has been developed. A prominent effect of these agents is the lowering of circulating FFA levels and it is believed, but not yet proven, that this interaction with FFAs constitutes a major mechanism behind the glucose-lowering effect of the TZDs. Copyright © 2002 John Wiley & Sons, Ltd. [source] Tissue-specific distribution and whole-body burden estimates of persistent organic pollutants in the bottlenose dolphin (Tursiops truncatus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010Jennifer E. Yordy Abstract Most exposure assessments for free-ranging cetaceans focus on contaminant concentrations measured in blubber, and few data are available for other tissues or the factors governing contaminant distribution among tissues. The goal of this study was to provide a detailed description of the distribution of persistent organic pollutants (POPs) within the common bottlenose dolphin (Tursiops truncatus) body and assess the role of lipid dynamics in mediating contaminant distribution. Thirteen tissues (brain, blubber, heart, liver, lung, kidney, mammary gland, melon, skeletal muscle, spleen, thyroid, thymus, and testis/uterus) were sampled during necropsy from bottlenose dolphins (n,=,4) and analyzed for lipid and 85 POPs, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers. Significant correlations between tissue POP concentrations and lipid suggest that distribution of POPs is generally related to tissue lipid content. However, blubber:tissue partition coefficients ranged widely from 0.753 to 6.25, suggesting that contaminant distribution is not entirely lipid-dependent. Tissue-specific and whole-body contaminant burdens confirmed that blubber, the primary site of metabolic lipid storage, is also the primary site for POP accumulation, contributing >90% to the whole-body burdens. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue concentrations. These results suggest that individuals with reduced blubber lipid may be at increased risk for exposure-related health effects. However, this study also provides evidence that the melon, a metabolically inert lipid-rich structure, may serve as an alternate depot for POPs, thus preventing the bulk of blubber contaminants from being directly available to other tissues. This unique physiological adaptation should be taken into consideration when assessing contaminant-related health effects in wild cetacean populations. Environ. Toxicol. Chem. 2010;29:1263,1273. © 2010 SETAC [source] A Gene Therapy Technology-Based Biomaterial for the Trigger-Inducible Release of Biopharmaceuticals in MiceADVANCED FUNCTIONAL MATERIALS, Issue 15 2010Michael M. Kämpf Abstract Gene therapy scientists have developed expression systems for therapeutic transgenes within patients, which must be seamlessly integrated into the patient's physiology by developing sophisticated control mechanisms to titrate expression levels of the transgenes into the therapeutic window. However, despite these efforts, gene-based medicine still faces security concerns related to the administration of the therapeutic transgene vector. Here, molecular tools developed for therapeutic transgene expression can readily be transferred to materials science to design a humanized drug depot that can be implanted into mice and enables the trigger-inducible release of a therapeutic protein in response to a small-molecule inducer. The drug depot is constructed by embedding the vascular endothelial growth factor (VEGF121) as model therapeutic protein into a hydrogel consisting of linear polyacrylamide crosslinked with a homodimeric variant of the human FK-binding protein 12 (FM), originally developed for gene therapeutic applications, as well as with dimethylsuberimidate. Administrating increasing concentrations of the inducer molecule FK506 triggers the dissociation of FM thereby loosening the hydrogel structure and releasing the VEGF121 payload in a dose-adjustable manner. Subcutaneous implantation of the drug depot into mice and subsequent administration of the inducer by injection or by oral intake triggers the release of VEGF121 as monitored in the mouse serum. This study is the first demonstration of a stimuli-responsive hydrogel that can be used in mammals to release a therapeutic protein on demand by the application of a small-molecule stimulus. This trigger-inducible release is a starting point for the further development of externally controlled drug depots for patient-compliant administration of biopharmaceuticals. [source] Heterologous expression of AtClo1, a plant oil body protein, induces lipid accumulation in yeastFEMS YEAST RESEARCH, Issue 3 2009Marine Froissard Abstract Proteomic approaches on lipid bodies have led to the identification of proteins associated with this compartment, showing that, rather than the inert fat depot, lipid droplets appear as complex dynamic organelles with roles in metabolism control and cell signaling. We focused our investigations on caleosin [Arabidopsis thaliana caleosin 1 (AtClo1)], a minor protein of the Arabidopsis thaliana seed lipid body. AtClo1 shares an original triblock structure, which confers to the protein the capacity to insert at the lipid body surface. In addition, AtClo1 possesses a calcium-binding domain. The study of plants deficient in caleosin revealed its involvement in storage lipid degradation during seed germination. Using Saccharomyces cerevisiae as a heterologous expression system, we investigated the potential role of AtClo1 in lipid body biogenesis and filling. The green fluorescent protein-tagged protein was correctly targeted to lipid bodies. We observed an increase in the number and size of lipid bodies. Moreover, transformed yeasts accumulated more fatty acids (+46.6%). We confirmed that this excess of fatty acids was due to overaccumulation of lipid body neutral lipids, triacylglycerols and steryl esters. We showed that the original intrinsic properties of AtClo1 protein were sufficient to generate a functional lipid body membrane and to promote overaccumulation of storage lipids in yeast oil bodies. [source] Controllable Soluble Protein Concentration Gradients in Hydrogel Networks,ADVANCED FUNCTIONAL MATERIALS, Issue 21 2008Brian J. Peret Abstract Here, controlled formation of sustained, soluble protein concentration gradients within hydrated polymer networks is reported. The approach involves spatially localizing proteins or biodegradable, protein-loaded microspheres within hydrogels to form a protein-releasing "depot." Soluble protein concentration gradients are then formed as the released protein diffuses away from the localized source. Control over key gradient parameters, including maximum concentration, gradient magnitude, slope, and time dynamics, is achieved by controlling the release of protein from the depot and subsequent transport through the hydrogel. Results demonstrate a direct relationship between the amount of protein released from the depot and the source concentration, gradient magnitude, and slope of the concentration gradient. In addition, an inverse relationship exists between the diffusion coefficient of protein within the hydrogel and the slope of the concentration gradient. The time dynamics of the concentration gradient profile can be directly correlated to protein release from the localized source, providing a mechanism for temporarily controlling gradient characteristics. Therefore, each key biologically relevant parameter associated with the protein concentration gradient can be controlled by defining protein release and diffusion. It is anticipated that the resulting materials may be useful in 3D cell culture systems, and in emerging tissue engineering approaches that aim to regenerate complex, functional tissues. [source] Clinical correlates of clozapine prescription for schizophrenia in ChinaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2007Yu-tao Xiang Abstract Aims Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile. This study examined the use of clozapine and its correlates in China. Methods Three hundred ninety-eight clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment instruments included the Structured Clinical Interview for DSM-IV, Brief Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms, Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health Organization Quality of Life Schedule-Brief version. Assessments were performed by the same investigator in both sites. Results Clozapine was prescribed to 15.6% of (n,=,62) patients. There was a wide inter-site variation between HK and BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side effects (EPS), having health insurance, use of depot and typical antipsychotic and anticholinergic drugs and benzodiazepines as well as history of suicidal attempts. On multiple logistic regression analysis, the number of hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy and co-prescription with anticholinergics were significantly associated with the prescription of clozapine. No significant differences were found between the clozapine and non-clozapine groups with regard to any of the quality of life domains. Conclusion A combination of economical and clinical factors, health policies and the characteristics of the treatment settings plays important roles in determining clozapine use. Clozapine appears to have little significant influence on quality of life in clinical stable Chinese patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd. [source] Prevalence of snoring and sleep-disordered breathing in a group of commercial bus drivers in Hong KongINTERNAL MEDICINE JOURNAL, Issue 4 2002D. S. C. Hui Abstract Objectives:,To assess the prevalence of sleep-disordered breathing (SDB) and its associated symptoms in a group of commercial bus drivers in Hong Kong. Methods:,Two hundred and sixteen of 410 bus drivers from three different shifts were interviewed with the Sleep & Health Questionnaire (SHQ) and the Epworth sleepiness scale (ESS) at a Hong Kong bus depot. Seventeen subjects from each shift were then randomly selected for at-home sleep study using the Mesam IV device (Madaus Medizin,Elektronik, Freiburg, Germany). Results:,There were 207 men and nine women (mean age 42.4 ± 7.5 years; body mass index (BMI) 25.4 ± 4.5 kg/m2; ESS 5.3 ± 4.2). From the SHQ it was discovered that: (i) daytime sleepiness was reported by 87 subjects (40%), (ii) snoring , 3 times per week was reported by 80 subjects (37%), (iii) witnessed apnoea was reported by 17 subjects (7.9%) and (iv) 29 subjects (13.4%) reported having fallen asleep during driving. Among the 51 subjects who underwent the at-home sleep study: (i) 31 subjects (61%) had respiratory disturbance index (RDI) , 5 per hour of sleep, (ii) 21 subjects (41%) had RDI , 10 per hour of sleep, (iii) 12 subjects (24%) had RDI , 15 per hour of sleep and (iv) 35 subjects (68.6%) snored objectively , 10% of the night. Ten subjects (20%) had RDI , 5 and sleepiness at work, while five subjects (9.8%) had RDI , 5 and ESS > 10. No significant differences were noted in the SHQ responses, ESS, objective snoring or RDI among the three groups. Multiple regression analysis showed that BMI and witnessed apnoea were the only positive independent predictors of RDI. Conclusions:,This study showed a high prevalence of objective snoring and SDB in a group of commercial bus drivers. Neither self-reported sleepiness nor the ESS could identify subjects with SDB. (Intern Med J 2002; 32: 149,157) [source] Solution of the Dial-a-Ride Problem with multi-dimensional capacity constraintsINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 3 2006K. I. Wong Abstract The Dial-a-Ride Problem (DARP) consists of planning routes and schedules for picking up and delivering users within user-specified time windows. Vehicles of a given fleet with limited capacity depart from and end at a common depot. The travel time of passengers cannot exceed a given multiple of the minimum ride time. Other constraints include vehicle capacity and vehicle route duration. In practice, scheduling is made more complicated by special user requirements and an inhomogeneous vehicle fleet. The transportation of elderly and handicapped people is an important example, as space for wheelchairs is limited and a lift is required. In this study, we present a modified insertion heuristic to solve the DARP with multi-dimensional capacity constraints, and the performance of the proposed algorithm is tested in simulation. We show that the proposed methodology is effective when compared with the classic algorithms. [source] The extraordinary ligand binding properties of human serum albuminIUBMB LIFE, Issue 12 2005Mauro Fasano Abstract Human serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites. HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and acts as a NO-carrier. The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins. Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized. [source] Changes in adipocytes and dendritic cells in lymph node containing adipose depots during and after many weeks of mild inflammationJOURNAL OF ANATOMY, Issue 6 2005Dawn Sadler Abstract The time course and cellular basis for inflammation-induced hypertrophy of adipose tissue were investigated over 20 weeks in mature male rats. Mild inflammation was induced by subcutaneous injection of 20 µg lipopolysaccharide into one hind-leg three times/week for 4 or 8 weeks, followed by up to 12 weeks ,rest' without intervention. Mean volume and frequency of apoptosis (TUNEL assay) were measured in adipocytes isolated from sites defined by their anatomical relations to lymph nodes, plus numbers of CCL21-stimulated lymph node-derived and adipose tissue-derived dendritic cells. Experimental inflammation increased dendritic cells and adipocyte apoptosis in the locally stimulated popliteal depot and the lymphoid tissue-associated regions of the contralateral popliteal and mesentery and omentum. Responses declined slowly after inflammation ended, but all measurements from the locally stimulated popliteal depot, and the omentum, were still significantly different from controls after 12 weeks rest. The locally stimulated popliteal adipose tissue enlarged by 5% within 4 weeks and remained larger than the control. We conclude that prolonged inflammation induces permanent enlargement, greater adipocyte turnover and increased dendritic cell surveillance in the adjacent adipose tissue and the omentum. The experiment suggests a mechanism for selective hypertrophy of lymphoid tissue-associated adipose tissue in chronic stress and inflammatory disorders, including impaired lymph drainage, Crohn's disease and HIV-associated lipodystrophy, and a link between evolutionary fitness, sexual selection and aesthetically pleasing body symmetry. It would be useful for further study of molecular mechanisms in inflammation-induced local hypertrophy of adipose tissue and development of specific therapies that avoid interference with whole-body lipid metabolism. [source] Treatment with oxidizing agents damages the inner membrane of spores of Bacillus subtilis and sensitizes spores to subsequent stressJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2004D.E. Cortezzo Abstract Aims:, To determine if treatment of Bacillus subtilis spores with a variety of oxidizing agents causes damage to the spore's inner membrane. Methods and Results:, Spores of B. subtilis were killed 80,99% with wet heat or a variety of oxidizing agents, including betadine, chlorine dioxide, cumene hydroperoxide, hydrogen peroxide, OxoneTM, ozone, sodium hypochlorite and t-butylhydroperoxide, and the agents neutralized and/or removed. Survivors of spores pretreated with oxidizing agents exhibited increased sensitivity to killing by a normally minimal lethal heat treatment, while spores pretreated with wet heat did not. In addition, spores treated with wet heat or the oxidizing agents, except sodium hypochlorite, were more sensitive to high NaCl in plating media than were untreated spores. The core region of spores treated with at least two oxidizing agents was also penetrated much more readily by methylamine than was the core of untreated spores, and spores treated with oxidizing agents but not wet heat germinated faster with dodecylamine than did untreated spores. Spores of strains with very different levels of unsaturated fatty acids in their inner membrane exhibited essentially identical resistance to oxidizing agents. Conclusions:, Treatment of spores with oxidizing agents has been suggested to cause damage to the spore's inner membrane, a membrane whose integrity is essential for spore viability. The sensitization of spores to killing by heat and to high salt after pretreatment with oxidizing agents is consistent with and supports this suggestion. Presumably mild pretreatment with oxidizing agents causes some damage to the spore's inner membrane. While this damage may not be lethal under normal conditions, the damaged inner membrane may be less able to maintain its integrity, when dormant spores are exposed to high temperature or when germinated spores are faced with osmotic stress. Triggering of spore germination by dodecylamine likely involves action by this agent on the spore's inner membrane allowing release of the spore core's depot of dipicolinic acid. Presumably dodecylamine more readily alters the permeability of a damaged inner membrane and thus more readily triggers germination of spores pretreated with oxidizing agents. Damage to the inner spore membrane by oxidizing agents is also consistent with the more rapid penetration of methylamine into the core of treated spores, as the inner membrane is likely the crucial permeability barrier to methylamine entry into the spore core. As spores of strains with very different levels of unsaturated fatty acids in their inner membrane exhibited essentially identical resistance to oxidizing agents, it is not through oxidation of unsaturated fatty acids that oxidizing agents kill and/or damage spores. Perhaps these agents work by causing oxidative damage to key proteins in the spore's inner membrane. Significance and Impact of the Study:, The more rapid heat killing and germination with dodecylamine, the greater permeability of the spore core and the osmotic stress sensitivity in outgrowth of spores pretreated with oxidizing agents is consistent with such agents causing damage to the spore's inner membrane, even if this damage is not lethal under normal conditions. It may be possible to take advantage of this phenomenon to devise improved, less costly regimens for spore inactivation. [source] The Beneficial Effect of Propolis on Fat Accumulation and Lipid Metabolism in Rats Fed a High-Fat DietJOURNAL OF FOOD SCIENCE, Issue 5 2009I. Ichi ABSTRACT:, This study examined whether propolis, which had many biological activities, affected body fat and lipid metabolism. Four-week-old Wistar rats were fed a control or propolis diet for 8 wk. The control group was fed a high-fat diet, the low and the high group were fed a high-fat diet supplemented with 0.5% (w/w) and 0.05% (w/w) propolis, respectively. The weight of total white adipose tissue of the high group was lower than that of the control group. The level of PPAR, protein in the adipose tissues of the high group was significantly lower than that of the control group. In plasma and the liver, the high group showed a significantly reduced level of cholesterol and triglyceride compared to the control group. The liver PPAR, protein level of the high group was significantly higher than that of the control group. The liver HMG-CoA reductase protein in the high group was also significantly lower than that in the control group. Results from rats on an olive oil loading test were used to investigate whether propolis inhibited triglyceride absorption. The serum triglyceride level of the group, which received propolis corresponding to the daily dose of the high group, was significantly lower than that of the control group. It is possible that the administration of propolis improves the accumulation of body fat and dyslipidemia via the change of the expression of proteins involved in adipose depot and lipid metabolism. [source] White Adipose Tissue: Getting NervousJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2003E. Fliers Abstract Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative physiology of fuel and energy metabolism, eating behaviour and the regulation of hormone secretion and sensitivity. WAT is controlled by humoral factors, para- and intracrine factors and by neural regulation. Sympathetic nerve fibres innervate WAT and stimulate lipolysis, leading to the release of glycerol and free fatty acids. In addition, recent research in rats has clearly shown a functional parasympathetic innervation of WAT. There appears to be a distinct somatotopy within the parasympathetic nuclei: separate sets of autonomic neurones in the brain stem innervate either the visceral or the subcutaneous fat compartment. We therefore propose that the central nervous system (CNS) plays a major role in the hitherto unexplained regulation of body fat distribution. Parasympathectomy induces insulin resistance with respect to glucose and fatty acid uptake in the innervated fat depot and has selective effects on local hormone synthesis. Thus, the CNS is involved not only in the regulation of hormone production by WAT, but also in its hormone sensitivity. The developments in this research area are likely to increase our insights in the pathogenesis of metabolic disorders such as hypertriglyceridemia, diabetes mellitus type 2 and lipodystrophy syndromes. [source] A detailed assessment of the pattern of moxidectin tissue distribution after pour-on treatment in calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2003J. M. Sallovitz The use of topical (pour-on) administration of endectocide drugs in cattle has reached world-wide acceptance. However, only limited information is available on the kinetic behaviour for topically administered moxidectin (MXD). To improve our understanding of the relationship between pharmacokinetics and efficacy for pour-on preparations, MXD concentration profiles were measured in tissues of endo- and ectoparasites location over 35 days postadministration. MXD distribution to the fluid content and mucosal tissue of the abomasum and different intestinal sections (duodenum, ileum, caecum and colon) was assessed. The comparative patterns of MXD distribution to skin and hypodermic tissue from different anatomical sites (backline, rib cage, thigh and face) were also investigated following the pour-on administration. Wide tissue distribution and long residence time characterized the kinetics of topically administered MXD. MXD was recovered between 1 and 35 days post-treatment in all the tissues investigated. The highest MXD availabilities were observed in the skin layers at the site of administration (backline) and in the fat tissue. The fluid contents of different intestinal sections showed MXD concentrations higher than those measured in their respective mucosal tissues, particularly at day 1 post-treatment. MXD concentrations in the skin (epidermis + dermis) were higher than those measured in the hypodermic tissue. Large differences in the availability of MXD in skin from different anatomical regions (backline > rib cage > thigh > face) were observed. The low plasma and the high skin availability indicate the formation of a skin depot of the drug, being released slowly to the plasma and reaching concentrations in systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after subcutaneous administration. These findings demonstrate that target parasites may be exposed to markedly different drug concentrations according to their location sites, which is particularly relevant for ectoparasites located in different anatomical regions. Knowledge of the tissue distribution of topically administered endectocides contributes to understand the differences observed in efficacy and/or persistence of activity and to optimize their use in cattle. [source] A branch-and-price-based large neighborhood search algorithm for the vehicle routing problem with time windowsNETWORKS: AN INTERNATIONAL JOURNAL, Issue 4 2009Eric Prescott-Gagnon Abstract Given a fleet of vehicles assigned to a single depot, the vehicle routing problem with time windows (VRPTW) consists of determining a set of feasible vehicle routes to deliver goods to a set of customers while minimizing, first, the number of vehicles used and, second, total distance traveled. A large number of heuristic approaches for the VRPTW have been proposed in the literature. In this article, we present a large neighborhood search algorithm that takes advantage of the power of branch-and-price which is the leading methodology for the exact solution of the VRPTW. To ensure diversification during the search, this approach uses different procedures for defining the neighborhood explored at each iteration. Computational results on the Solomo's and the Gehring and Homberge's benchmark instances are reported. Compared to the best known methods, the proposed algorithm produces better solutions, especially on the largest instances where the number of vehicles used is significantly reduced. © 2009 Wiley Periodicals, Inc. NETWORKS, 2009 [source] The one-commodity pickup-and-delivery traveling salesman problem: Inequalities and algorithmsNETWORKS: AN INTERNATIONAL JOURNAL, Issue 4 2007Hipólito Hernández-Pérez Abstract This article concerns the "One-commodity Pickup-and-Delivery Traveling Salesman Problem" (1-PDTSP), in which a single vehicle of fixed capacity must either pick up or deliver known amounts of a single commodity to a given list of customers. It is assumed that the product collected from the pickup customers can be supplied to the delivery customers, and that the initial load of the vehicle leaving the depot can be any quantity. The problem is to find a minimum-cost sequence of the customers in such a way that the vehicle's capacity is never exceeded. This article points out a close connection between the 1-PDTSP and the classical "Capacitated Vehicle Routing Problem" (CVRP), and it presents new inequalities for the 1-PDTSP adapted from recent inequalities for the CVRP. These inequalities have been implemented in a branch-and-cut framework to solve to optimality the 1-PDTSP that outperforms a previous algorithm (Hernández-Pérez and Salazar-González, Discrete Appl Math 145 (2004), 126,139). Larger instances (with up to 100 customers) are now solved to optimality. The classical "Traveling Salesman Problem with Pickups and Deliveries" (TSPPD) is a particular case of the 1-PDTSP, and this observation gives an additional motivation for this article. The here-proposed algorithm for the 1-PDTSP was able to solve to optimality TSPPD instances with up to 260 customers. © 2007 Wiley Periodicals, Inc. NETWORKS, Vol. 50(4), 258,272 2007 [source] Leptin and Insulin Action in the Central Nervous SystemNUTRITION REVIEWS, Issue 2002Daniel Porte Jr M.D. Body adiposity is known to be carefully regulated and to remain relatively stable for long periods of time in most mammalian species. This review summarizes old and recent data implicating insulin and leptin as key circulating signals to the central nervous system, particularly the ventral hypothalamus, in communicating thesizeand thedistribution of body fat stores. This input ultimately alters food intake and energy expenditure to maintain constancy of the adipose depot. The key primary neurons in the arcuate nucleus containing NPY/AgRP and POMC/CART appear be critical constituents of the CNS regulating system, and are shown to contribute to anabolic and catabolic signaling systems to complete the feedback loop. New data to indicate shared intracellular signaling from leptin and insulin is provided. The satiety system for meals, consisting of neural afferents to the hind-brain from the gastrointestinal tract, is described and its effectiveness is shown to vary with the strength of the insulin and leptin signals. This provides anefferent mechanism that plays a key role in a complex feedback system that allows intermittent meals to vary from day to day, but provides appropriate long-term adjustment to need. Recently described contributions of this system to obesity are described and potential therapeutic implications are discussed. [source] Numerical Simulation of Pollution Dispersion over Real TerrainPROCEEDINGS IN APPLIED MATHEMATICS & MECHANICS, Issue 1 2003k Bene The paper presents a mathematical and numerical investigation of the atmospheric boundary layer (ABL) flow over coal depot. Two mathematical models have been mentioned based upon: 1) the RANS equations in the conservative form and 2) the Boussinesq approximation of RANS equations in the non,conservative form, both formulated for an incompressible flow with a simple algebraic turbulence closure and given stationary boundary conditions. Also pollution dispersion of passive pollutants has been considered. [source] Pharmacokinetics and efficacy of a direct switch from conventional depot to risperidone long-acting injection in Chinese patients with schizophrenic and schizoaffective disordersPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2009Ying-Ching Lai md Aims:, This 12-week open-label study was designed to investigate the pharmacokinetics and efficacy of a direct switch from a conventional depot to long-acting injectable risperidone in patients with schizophrenia and schizoaffective disorder. Methods:, Men or women from 18 to 65 years old with a diagnosis of schizophrenia or schizoaffective disorder were eligible for participation if they had been treated with conventional depot for at least 8 weeks before study entry. Intramuscular long-acting risperidone was administered starting from 25 mg, with the dose flexibly adjusted every two weeks for 12 weeks from week 4. Results:, Of the 25 patients enrolled in this study, 21 completed at least one post-baseline assessment and were thus included in the analysis. The mean serum concentration of risperidone plus 9-hydroxyrisperidone was 29.1 ng/mL at the 12th week after switching, with an average injection dose of 31.25 mg long-acting risperidone every two weeks. The levels of active moiety of risperidone seemed to be higher in Chinese patients compared to those in Caucasian patients. Positive and Negative Syndrome Scale total scores (from 67.5 to 56.4; P = 0.002), scores for negative symptoms (P = 0.006) and general symptoms (P = 0.001) were improved significantly 12 weeks after the switch. Mean Extrapyramidal Symptom Rating Scale scores were improved significantly from 20.1 to 5.5 (P < 0.001). Significantly decreased levels of cholesterol and triglyceride were found at the 12th week. The levels of fasting glucose, low-density lipoprotein, high-density lipoprotein and bodyweight remained unchanged. Conclusions:, These findings suggest that switching from conventional depot to long-acting risperidone is feasible with the advantage of symptom reduction and side-effect profile decrement. [source] Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestationTHE JOURNAL OF PHYSIOLOGY, Issue 1 2005B. S. Mühlhäusler In the present study, our aim was to determine whether intrafetal glucose infusion increases fetal adiposity, synthesis and secretion of leptin and regulates gene expression of the ,appetite regulatory' neuropeptides neuropepetide Y (NPY), agouti-related peptide (AGRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and receptors (leptin receptor (OB-Rb) and melancortin 3 receptor (MC3R)) within the fetal hypothalamus. Glucose (50% dextrose in saline) or saline was infused (7.5 ml h,1) into fetal sheep between 130 and 140 days gestation (term = 150 ± 3 days gestation). Glucose infusion increased circulating glucose and insulin concentrations, mean lipid locule size (532.8 ± 3.3 ,m2versus 456.7 ± 14.8 ,m2) and total unilocular fat mass (11.7 ± 0.6 g versus 8.9 ± 0.6 g) of the perirenal fat depot. The expression of OB-Rb mRNA was higher in the ventromedial nucleus compared to the arcuate nucleus of the hypothalamus in both glucose and saline infused fetuses (F= 8.04; P < 0.01) and there was a positive correlation between expression of OB-Rb and MC3R mRNA in the arcuate nucleus (r= 0.81; P < 0.005). Glucose infusion increased mRNA expression for POMC, but not for the anorectic neuropeptide CART, or the orexigenic neuropeptides NPY and AGRP, in the arcuate nucleus of the fetal hypothalamus. These findings demonstrate that increased circulating glucose and insulin regulate gene expression of the neuropeptides within the fetal hypothalamus that are part of the neural network regulating energy balance in adult life. [source] Decorrugation, edge detection, and modelling of total field magnetic observations from a historic town site, Yellowstone National Park, USAARCHAEOLOGICAL PROSPECTION, Issue 1 2010Steven D. Sheriff Abstract Cinnabar, Montana is a historic town site and railroad depot near the northern edge of Yellowstone National Park and was inhabited between 1883 and 1903. Remains of foundations and old photographs help determine the area of the town, but the south and east limits are unknown. We acquired total field magnetic intensity data to help determine the full extent of the town. Randomly distributed ferrous magnetic sources on the surface and typical noise associated with acquisition complicate the signal. To separate signal and noise we applied filtering and edge detection techniques common in the aeromagnetic industry to our data. Regional removal, decorrugation, upward continuation, and edge detection successfully separated signal and noise. Following filtering, we extracted two larger anomalies from the data set. For those two anomalies, we estimated the edges of their causative sources by calculating the maxima in the horizontal gradient of their anomalies and by inverse modelling those sources; both methods yield similar results. An archaeological test unit excavation within one of the anomalies clearly indicates the remains of buried domestic features, the foundation to a house or other building associated with the late nineteenth to early twentieth century use of Cinnabar. Thus the southeast extent of Cinnabar is greater than previously thought. The lack of surface indicators or adequate historic photography precluded the identification of this buried feature without the aid of the magnetic study. Copyright © 2009 John Wiley & Sons, Ltd. [source] Development and characterization of a fusion protein between thermally responsive elastin-like polypeptide and interleukin-1 receptor antagonist: Sustained release of a local antiinflammatory therapeuticARTHRITIS & RHEUMATISM, Issue 11 2007Mohammed F. Shamji Objective Interleukin-1 receptor antagonist (IL-1Ra) has been evaluated for the intraarticular treatment of osteoarthritis. Such administration of proteins may have limited utility because of their rapid clearance and short half-life in the joint. The fusion of a drug to elastin-like polypeptides (ELPs) promotes the formation of aggregating particles that form a "drug depot" at physiologic temperatures, a phenomenon intended to prolong the presence of the drug. The purpose of this study was to develop an injectable drug depot composed of IL-1Ra and ELP domains and to evaluate the properties and bioactivity of the recombinant ELP-IL-1Ra fusion protein. Methods Fusion proteins between IL-1Ra and 2 distinct sequences and molecular weights of ELP were overexpressed in Escherichia coli. Environmental sensitivity was demonstrated by turbidity and dynamic light scattering as a function of temperature. IL-1Ra domain activity was evaluated by surface plasmon resonance, and in vitro antagonism of IL-1,mediated lymphocyte and thymocyte proliferation, as well as IL-1,induced tumor necrosis factor , (TNF,) expression and matrix metalloproteinase 3 (MMP-3) and ADAMTS-4 messenger RNA expression in human intervertebral disc fibrochondrocytes. IL-1Ra immunoreactivity was assessed before and after proteolytic degradation of the ELP partner. Results Both fusion proteins underwent supramolecular aggregation at subphysiologic temperatures and slowly resolubilized at 37°C. Interaction with IL-1 receptor was slower in association but equivalent in dissociation as compared with the commercial antagonist. Anti,IL-1 activity was demonstrated by inhibition of lymphocyte and thymocyte proliferation and by decreased TNF, expression and ADAMTS-4 and MMP-3 transcription by fibrochondrocytes. ELP domain proteolysis liberated a peptide of comparable size and immunoreactivity as the commercial IL-1Ra. This peptide was more bioactive against lymphocyte proliferation, nearly equivalent to the commercial antagonist. Conclusion The ELP-IL-1Ra fusion protein proved to retain the characteristic ELP inverse phase-transitioning behavior as well as the bioactivity of the IL-1Ra domain. This technology represents a novel drug carrier designed to prolong the presence of bioactive peptides following intraarticular delivery. [source] Individual variations of serum testosterone in patients with prostate cancer receiving androgen deprivation therapyBJU INTERNATIONAL, Issue 3 2009Juan Morote OBJECTIVE To analyse individual variations in serum testosterone level, the cumulative rate of ,breakthrough' increases over castrate levels, and to evaluate whether the increases can be predicted. PATIENTS AND METHODS Serum testosterone levels were determined every 6 months over 3 years in 73 consecutive patients with prostate cancer who were medically castrated, prospectively enrolled in a single tertiary academic centre. Patients recruited for this study were being treated with a 3-monthly depot of luteinizing hormone-releasing hormone agonist over 6,48 months. Serum testosterone was measured using a chemiluminescent assay with a lower sensitivity level of 15 ng/dL and interassay coefficient of variation of 25% at low testosterone concentrations. RESULTS Individual variations could not be explained by the interassay variation coefficient in 26% of the patients. The rate of breakthrough increases >50 ng/dL increased from 12.3% at the first determination to 24.7% at the third, then remaining stable. The rate of breakthrough increases of 20,50 ng/dL increased from 27.4% at the first determination to 31.5% at the second, and then remained stable. A first determination of <20 ng/dL provided an 11.4% probability for future increases of >50 ng/dL, with a 5.7% probability if two consecutive determinations were <20 ng/dL and a null probability when three consecutive determinations were <20 ng/dL. CONCLUSIONS Individual variations in serum testosterone level cannot be explained by the coefficient of variation of the assay in a quarter of patients who are medically castrated. Breakthrough increases over castrate levels increase over time and those of >50 ng/dL can be predicted from the previous levels. [source] Intrabdominal fat is related to metabolic risk factors in Hispanic Americans, African Americans and in girlsACTA PAEDIATRICA, Issue 12 2009K Casazza Abstract Aim:, This study aimed to test the association of individual adipose depots on cardiometabolic outcomes, whether the association varied by depot and if the associations differed by race/ethnicity or gender in early pubertal children. Methods:, Three hundred and twenty children (53% male) aged 7,12 years self-identified as African American (AA; n = 114), European American (EA; n = 120) or Hispanic American (HA; n = 86) participated. Insulin dynamics were assessed by intravenous glucose tolerance test; body composition with DXA; fat distribution with CT. Results:, AA had the least fat in each depot and HA had the most. Fat accumulation negatively impacted cardiometabolic outcomes independent of race/ethnicity or gender. AA and females were reproductively more mature. In AA and HA, each measure of adiposity influenced the insulin sensitivity index (SI), whereas intra-abdominal adipose tissue (IAAT) did not contribute to SI in EA. IAAT was positively associated with blood pressure in AA only. In females, adiposity adversely influenced cardiometabolic outcomes such that total fat mass, IAAT and/or SAAT was inversely associated with SI, and positively associated with blood pressure and fasting insulin. Conclusion:, IAAT is uniquely related to metabolic risk factors in Hispanic Americans, African Americans and girls, suggesting that either the threshold for adverse effects of IAAT is lower, or the IAAT metabolism differs in these groups. [source] Ocular toxicity of fluoroquinolonesCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 6 2007Andrew M Thompson FRANZCO Abstract The ocular toxicity of fluoroquinolones and the risks of their use in the treatment of ocular infection were reviewed. Systematic identification, selection, review and synthesis of published English-language studies relating to fluoroquinolone use and safety in animals and humans was conducted. Although not free of complications, fluoroquinolones are generally safe when used to treat ocular infection. Ocular toxicity appears to be dose-dependent and results from class-effects and specific fluoroquinolone structures. Phototoxicity and neurotoxicity have been reported, and toxic effects on ocular collagen may be associated with Achilles tendinopathy. Corneal precipitation may provide an advantageous drug depot but delay healing and result in corneal perforation in approximately 10% of cases. Although human toxicity studies are limited, the current recommended dose for intracameral injection of ciprofloxacin is less than 25 ,g. Intravitreal injections of ciprofloxacin 100 ,g, ofloxacin 50 ,g/mL, trovafloxacin 25 ,g or less, moxifloxacin 160 ,g/0.1 mL or less and pefloxacin 200 ,g/0.1 mL are considered safe. [source] | ||||||||||||||||||||||||||||||||||||||||