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Metabolic Alterations (metabolic + alteration)
Selected AbstractsCerebral metabolic alterations in children with diabetic ketoacidosisDIABETIC MEDICINE, Issue 5 2005N. S. Glaser No abstract is available for this article. [source] Adiponectin and visfatin concentrations in children treated with valproic acidEPILEPSIA, Issue 2 2008Markus Rauchenzauner Summary Chronic antiepileptic therapy with valproic acid (VPA) is associated with increased body weight and insulin resistance in adults and children. Attempts to determine the underlying pathophysiologic mechanisms have failed. Adipocytokines have recently been defined as a link between glucose and fat metabolism. We herein demonstrate that VPA-associated overweight is accompanied by lower adiponectin and higher leptin concentrations in children. The absence of any relationship with visfatin concentration does not suggest a role of this novel insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore, adiponectin and leptin but not visfatin may be considered as potential regulators of glucose and fat metabolism during VPA-therapy. [source] Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytesGLIA, Issue 13 2010Astrid Bottelbergs Abstract Ablation of functional peroxisomes from all neural cells in Nestin-Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp-Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between these neurological anomalies and the known metabolic alterations, namely the accumulation of very long-chain fatty acids (VLCFA) and reduction of plasmalogens, has not been established. We now focused on the role of peroxisomes in neurons and astrocytes. A neuron-specific peroxisome knockout model, NEX-Pex5, showed neither microscopic nor metabolic abnormalities indicating that the lack of functional peroxisomes within neurons does not cause axonal damage. Axonal integrity and normal behavior was also preserved when peroxisomes were deleted from astrocytes in GFAP-Pex5,/, mice. Nevertheless, peroxisomal metabolites were dysregulated in brain including a marked accumulation of VLCFA and a slight reduction in plasmalogens. Interestingly, despite minor targeting of oligodendrocytes in GFAP-Pex5,/, mice, these metabolic perturbations were also present in isolated myelin indicating that peroxisomal metabolites are shuttled between different brain cell types. We conclude that absence of peroxisomal metabolism in neurons and astrocytes does not provoke the neurodegenerative phenotype observed after deleting peroxisomes from oligodendrocytes. Lack of peroxisomal metabolism in astrocytes causes increased VLCFA levels in myelin, but this has no major impact on neurological functioning. © 2010 Wiley-Liss, Inc. [source] Intrahepatic amino acid and glucose metabolism in a D -galactosamine,induced rat liver failure modelHEPATOLOGY, Issue 2 2001Kosuke Arai A better understanding of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and other nonsurgical medical therapies for FHF. We used an isolated perfused liver system in combination with a mass-balance model of hepatic intermediary metabolism to generate a comprehensive map of metabolic alterations in the liver in FHF. To induce FHF, rats were fasted for 36 hours, during which they received 2 D -galactosamine injections. The livers were then perfused for 60 minutes via the portal vein with amino acid,supplemented Eagle minimal essential medium containing 3% wt/vol bovine serum albumin and oxygenated with 95% O2/5% CO2. Control rats were fasted for 36 hours with no other treatment before perfusion. FHF rat livers exhibited reduced amino acid uptake, a switch from gluconeogenesis to glycolysis, and a decrease in urea synthesis, but no change in ammonia consumption compared with normal fasted rat livers. Mass-balance analysis showed that hepatic glucose synthesis was inhibited as a result of a reduction in amino acid entry into the tricarboxylic acid cycle by anaplerosis. Furthermore, FHF inhibited intrahepatic aspartate synthesis, which resulted in a 50% reduction in urea cycle flux. Urea synthesis by conversion of exogenous arginine to ornithine was unchanged. Ammonia removal was quantitatively maintained by glutamine synthesis from glutamate and a decrease in the conversion of glutamate to ,-ketoglutarate. Mass-balance analysis of hepatic metabolism will be useful in characterizing changes during FHF, and in elucidating the effects of nutritional supplements and other treatments on hepatic function. [source] Screening of glucose/insulin metabolic alterations in men with multiple skin tags on the neckJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 10 2008Emilio Sudy Summary Multiple skin tags appear associated with abnormalities in glucose/insulin metabolism. Clinical and metabolic glucose/insulin characteristics of men with multiple (8 or more) skin tags on the neck were compared with a control group with few or none. Both groups were divided in two subgroups according to normal or abnormal laboratory findings. In the study subgroup with normal laboratory findings the number of skin tags varied from 8,33, whereas in those with abnormal laboratory findings the range was 9,65. Eight or more skin tags were related with statistically significant laboratory glucose/insulin abnormalities: basal hyperinsulinemia (p<0.002), postprandial hyperinsulinemia (p<0.003), and postprandial hyperglycemia (p<0.01). In the multiple skin tag group 77 % had diverse laboratory abnormalities, including insulin resistance, basal hyperinsulinemia, postprandial hyperinsulinemia, glucose intolerance or type 2 diabetes, in contrast with the control group, where only 33 % showed laboratory abnormalities. One-third of the study group had acanthosis nigricans. Only 15 % of patients with metabolic abnormalities did not show any cutaneous expression of glucose/insulin alterations (9 or more skin tags on the neck, acanthosis nigricans, or waist circumference greater than 95 cm). Multiple skin tags were more sensitive than acanthosis nigricans in identifying those with alterations in the glucose/insulin metabolism (77 vs. 32 % respectively), although less specific (68 vs.100%). Multiple skin tags should raise suspicion of insulin resistance or hyperinsulinemia. [source] Diabetes and mitochondrial bioenergetics: Alterations with ageJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2003Fernanda M. Ferreira Abstract Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, some of the results reported are controversial, since experimental conditions, such as aging, and/or strain of animals used were different. The purpose of this study was to evaluate the metabolic changes in liver mitochondria, both in the presence of severe hyperglycaemia (STZ-treated rats) and mild hyperglycaemia (Goto-Kakizaki (GK) rats). Moreover, metabolic alterations were evaluated both at initial and at advanced states of the disease. We observed that both models of type 1 and type 2 diabetes presented alterations on respiratory chain activity. Because of continual severe hyperglycaemia, 9 weeks after the induction of diabetes, the respiratory function declined in STZ-treated rats, as observed by membrane potential and respiratory ratios (RCR, P/O, and FCCP-stimulated respiration) assessment. In contrast, GK rats of 6 months age presented increased respiratory ratios. To localize which respiratory complexes are affected by diabetes, enzymatic respiratory chain activities were evaluated. We observed that succinate dehydrogenase and cytochrome c oxidase activities were significantly augmented both in STZ-treated rats and GK rats of 6 months age. Moreover, H+ -ATPase activity was also significantly increased in STZ-treated rats with 3 weeks of diabetes and in GK rats of 6 months age as compared to controls. Therefore, these results clearly suggest that both animal models of diabetes present some metabolic adjustments in order to circumvent the deleterious effects promoted by the high glucose levels typical of the disease. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:214,222, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10081 [source] Genome-wide screen identifies Escherichia coli TCA-cycle-related mutants with extended chronological lifespan dependent on acetate metabolism and the hypoxia-inducible transcription factor ArcAAGING CELL, Issue 5 2010Stavros Gonidakis Summary Single-gene mutants with extended lifespan have been described in several model organisms. We performed a genome-wide screen for long-lived mutants in Escherichia coli, which revealed strains lacking tricarboxylic acid (TCA)-cycle-related genes that exhibit longer stationary-phase survival and increased resistance to heat stress compared to wild-type. Extended lifespan in the sdhA mutant, lacking subunit A of succinate dehydrogenase, is associated with the reduced production of superoxide and increased stress resistance. On the other hand, the longer lifespan of the lipoic acid synthase mutant (lipA) is associated with reduced oxygen consumption and requires the acetate-producing enzyme pyruvate oxidase, as well as acetyl-CoA synthetase, the enzyme that converts extracellular acetate to acetyl-CoA. The hypoxia-inducible transcription factor ArcA, acting independently of acetate metabolism, is also required for maximum lifespan extension in the lipA and lpdA mutants, indicating that these mutations promote entry into a mode normally associated with a low-oxygen environment. Because analogous changes from respiration to fermentation have been observed in long-lived Saccharomyces cerevisiae and Caenorhabditis elegans strains, such metabolic alterations may represent an evolutionarily conserved strategy to extend lifespan. [source] Malnutrition and hypermetabolism are not risk factors for the presence of hepatic encephalopathy: A cross-sectional studyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008Peter Sörös Abstract Background and Aim:, Hepatic encephalopathy is a frequent complication of cirrhosis. The present retrospective investigation was conducted to characterize metabolic alterations in cirrhotic patients with and without hepatic encephalopathy. We tested the hypothesis that reduced nutritional status or the degree of tissue catabolism are associated with the presence of hepatic encephalopathy. Methods:, We investigated 223 patients with histologically confirmed nonalcoholic cirrhosis without hepatic encephalopathy and with hepatic encephalopathy (grades 1,3). To assess liver function, nutritional status, and energy metabolism, a variety of biochemical and clinical tests were performed including anthropometric measurements, bioelectrical impedance analysis, and indirect calorimetry. Results:, Nutritional status and tissue catabolism were not significantly different between patients with and without hepatic encephalopathy. Conclusions:, Our data do not support the hypothesis that malnutrition or tissue catabolism are independent risk factors for the presence of hepatic encephalopathy in patients with nonalcoholic cirrhosis. [source] Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2007Ewert Schulte-Frohlinde Abstract Background and Aim:, Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. Methods:, Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. Results:, In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. Conclusions:, The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation. [source] Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illnessJOURNAL OF INTERNAL MEDICINE, Issue 2 2006P. E. MOLINA Abstract. Traumatic injury, surgical interventions and sepsis are amongst some of the clinical conditions that result in marked activation of neuroendocrine and opiate responses aimed at restoring haemodynamic and metabolic homeostasis. The central activation of the neuroendocrine and opiate systems, known collectively as the stress response, is elicited by diverse physical stressor conditions, including ischaemia, glucopenia and inflammation. The role of the hypothalamic,pituitary,adrenal axis and sympathetic nervous system in counterregulation of haemodynamic and metabolic alterations has been studied extensively. However, that of the endogenous opiates/opioid system is still unclear. In addition to activation of the opiate receptor through the endogenous release of opioids, pharmacotherapy with opiate receptor agonists is frequently used for sedation and analgesia of injured, septic and critically ill patients. How this affects the haemodynamic, cardiovascular, metabolic and immune responses is poorly understood. The variety of opiate receptor types, their specificity and ubiquitous location both in the central nervous system and in the periphery adds additional complicating factors to the clear understanding of their contribution to the stress response to the various physical perturbations. This review aims at discussing scientific evidence gathered from preclinical studies on the role of endogenous opioids as well as those administered as pharmacological agents on the host cardiovascular, neuroendocrine, metabolic and immune response mechanisms critical for survival from injury in perspective with clinical observations that provide parallel assessment of relevant outcome measures. When possible, the clinical relevance and corresponding scenarios where this evidence can be integrated into our understanding of the clinical implications of opiate effects will be examined. Overall, the scientific basis to enhance clinical judgment and expectations when using opioid sedation and analgesia in the management of the injured, septic or postsurgical patient will be discussed. [source] MRI of late microstructural and metabolic alterations in radiation-induced brain injuriesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2009Kevin C. Chan BEng Abstract Purpose To evaluate the late effects of radiation-induced damages in the rat brain by means of in vivo multiparametric MRI. Materials and Methods The right hemibrains of seven Sprague-Dawley rats were irradiated with a highly collimated 6 MV photon beam at a single dose of approximately 28 Gy. Diffusion tensor imaging (DTI), proton MR spectroscopy (1H-MRS), T2-weighted imaging, and T1-weighted imaging were performed to the same animals 12 months after radiation treatment. Results Compared with the contralateral side, a significantly higher percentage decrease in fractional anisotropy was observed in the ipsilateral fimbria of hippocampus (29%) than the external capsule (8%) in DTI, indicating the selective vulnerability of fimbria to radiation treatment. Furthermore, in 1H-MRS, significantly higher choline, glutamate, lactate, and taurine peaks by 24%, 25%, 87%, and 58%, respectively, were observed relative to creatine in the ipsilateral brain. Postmortem histology confirmed these white matter degradations as well as glial fibrillary acidic protein and glutamine synthetase immunoreactivity increase in the ipsilateral brain. Conclusion The microstructural and metabolic changes in late radiation-induced brain injuries were documented in vivo. These multiparametric MRI measurements may help understand the white matter changes and neurotoxicity upon radiation treatment in a single setting. J. Magn. Reson. Imaging 2009;29:1013,1020. © 2009 Wiley-Liss, Inc. [source] Ranolazine Attenuates Palmitoyl- l -carnitine-induced Mechanical and Metabolic Derangement in the Isolated, Perfused Rat HeartJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2000KAZUYASU MARUYAMA The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl- l -carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl- l -carnitine (4 ,m) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl- l -carnitine were attenuated by ranolazine (5, 10, and 20 ,m) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mm) did not attenuate palmitoyl- l -carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl- l -carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl- l -carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase. [source] Activation of the Innate Immune System and Alcoholic Liver Disease: Effects of Ethanol per se or Enhanced Intestinal Translocation of Bacterial Toxins Induced by Ethanol?ALCOHOLISM, Issue 2005Christiane Bode The mechanisms involved in the ethanol-induced activation of monocytes/macrophages (including Kupffer cells) are however, still a matter of debate. The brief review will summarize the published data from the literature on the two main pathomechanisms discussed until now: I) Gut-derived bacterial toxins, specially endotoxin; and II) metabolic changes induced by alcohol oxidation (independent of mechanism I). For pathomechanism I, clear evidence has been published from numerous groups: Alcohol induces mucosal injury in the upper gastrointestinal tract and leads to marked increase in the permeability of the gut mucosa to macromolecules such as endotoxin. The resulting endotoxemia then leads to activation of Kupffer cells and other macrophages. The increased release of pro-inflammatory mediators (e.g., TNF-,, Il-1, reacting oxygen species) and infiltration of other inflammatory cells (e.g., neutrophils) finally causes liver damage. Regarding the second pathomechanism it has repeatedly been argued that the metabolic alterations which are induced by chronic administration of ethanol to rats or mice might increase the sensitivity of monocytes/macrophages to secrete TNF-, and other pro-inflammatory mediators thereby increasing the susceptibility to ethanol-induced liver injury. However, in all feeding experiments the effect of ethanol on intestinal permeability and enhanced translocation of bacterial toxins (endotoxin) is likely to occur (or at least cannot be excluded). The latter holds true also for experiments using isolated macrophages/Kupffer cells from ethanol fed animals. Therefore, to clarify whether or not alterations related to ethanol metabolism ("direct" effects of ethanol) contribute to the activation of the innate immune system studies using germ-free animals are needed to exclude the "indirect" effect of ethanol via gut-derived bacterial toxins. [source] Characterization of the Streptococcus sobrinus acid-stress response by interspecies microarrays and proteomicsMOLECULAR ORAL MICROBIOLOGY, Issue 5 2010A.R. Martinez Summary Streptococcus mutans and Streptococcus sobrinus are considered the primary organisms responsible for human dental caries. The ability to generate acids and to adapt to low pH conditions is directly associated with the cariogenic potential of these bacteria. To survive acidic conditions, both species have been shown to mount an acid-tolerance response (ATR). However, previous characterization of the S. sobrinus ATR identified critical differences in the mechanisms of acid adaptation between S. mutans and S. sobrinus. Here, interspecies microarray and proteomic approaches were used to identify novel, previously unrecognized genes and pathways that participate in the S. sobrinus acid-stress response. The results revealed that, among other things, metabolic alterations that enhance energy generation and upregulation of the malolactic fermentation enzyme activity constitute important acid-resistance properties in S. sobrinus. Some of these acid adaptive traits are shared by S. mutans and might be considered optimal targets for therapeutic treatments designed to control dental caries. [source] Endotoxemia does not limit energy supply in exercising rat skeletal muscleMUSCLE AND NERVE, Issue 4 2008Benoit Giannesini PhD Abstract Although depletion in high-energy phosphorylated compounds and mitochondrial impairment have been reported in septic skeletal muscle at rest, their impact on energy metabolism has not been documented during exercise. In this study we aimed to investigate strictly gastrocnemius muscle function non-invasively, using magnetic resonance techniques in endotoxemic rats. Endotoxemia was induced by injecting animals intraperitoneally at t0 and t0 + 24 h with Klebsiella pneumoniae lipopolysaccharides (at 3 mg kg,1). Investigations were performed at t0 + 48 h during a transcutaneous electrical stimulation protocol consisting of 5.7 min of repeated isometric contractions at a frequency of 3.3 HZ. Endotoxin treatment produced a depletion in basal phosphocreatine content and a pronounced reduction in oxidative adenosine triphosphate (ATP) synthesis capacity, whereas the resting ATP concentration remained unchanged. During the stimulation period, endotoxemia caused a decrease in force-generating capacity that was fully accounted for by the loss of muscle mass. It further induced an acceleration of glycolytic ATP production and an increased accumulation of adenosine diphosphate (ADP, an important mitochondrial regulator) that allowed a near-normal rate of oxidative ATP synthesis. Finally, endotoxemia did not affect the total rate of ATP production or the ATP cost of contraction throughout the whole stimulation period. These data demonstrate that, in an acute septic phase, metabolic alterations in resting muscle do not impact energy supply in exercising muscle, likely as a result of adaptive mechanisms. Muscle Nerve, 2008 [source] 1H- and 31P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral componentsNMR IN BIOMEDICINE, Issue 5 2001Fritz-Georg Lehnhardt Abstract In vitro NMR spectrocopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. 31P- and 1H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. 31P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the 1H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the 31P- and the 1H-spectra. Based on the total detectable 31P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p,=,0.0003), whereas the level of sphingomyelin was about 45% lower in primary gioblastomas than in primary astrocytomas (p,=,0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p,=,0.0103) and ,23% (p,=,0.0314) change, respectively]. 1H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the 31P-spectra, the 1H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. 1H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution 1H- and 31P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism. Copyright © 2001 John Wiley & Sons, Ltd. [source] Hypoglycaemic activity of Pterocarpus marsupium Roxb.PHYTOTHERAPY RESEARCH, Issue 1 2006S. P. Dhanabal Abstract The antidiabetic activity of various subfractions of the alcohol extract of the bark of Pterocarpus marsupium Roxb. was evaluated in alloxan-induced diabetic rats. The effect of these extracts on lipid profile and liver function tests were also assessed to evaluate their activity in controlling diabetes related metabolic alterations. The parameters measured were plasma glucose, total protein, cholesterol, triglycerides, alkaline phosphatase, SGOT and SGPT. The results indicate the effective role of Pterocarpus marsupium on the above mentioned parameters indicating that Pterocarpus marsupium can also control the diabetes related metabolic alterations apart from controlling the glucose levels. Among the fractions tested the butanol subfraction was found to be more active in comparison with other subfractions. It can be concluded that the butanol subfraction of the alcohol extract of Pterocarpus marsupium exhibits significant antidiabetic activity and corrects the metabolic alterations in diabetic rats and this activity may resemble insulin-like properties. Copyright © 2006 John Wiley & Sons, Ltd. [source] Review article: The impact of obesity on reproduction in women with polycystic ovary syndromeBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2006R Pasquali The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS. [source] Increased expression of TDP-43 in the skin of amyotrophic lateral sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010M. Suzuki Suzuki M, Mikami H, Watanabe T, Yamano T, Yamazaki T, Nomura M, Yasui K, Ishikawa H, Ono S. Increased expression of TDP-43 in the skin of amyotrophic lateral sclerosis. Acta Neurol Scand: 2010: 122: 367,372. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives,,, Transactivation-responsive DNA-binding protein-43 (TDP-43) was indentified as a major component of the ubiquitin-positive inclusions in sporadic amyotrophic lateral sclerosis (ALS). However, there has been no study of TDP-43 in ALS skin. The present study investigates TDP-43 in ALS skin. Materials and methods,,, We made a quantitative immunohistochemical study of the expression of TDP-43 in the skin from 15 patients with ALS and 15 control subjects. Results,,, The proportion of TDP-43-positive (TDP-43+) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.62, P < 0.02) between the proportion and duration of illness in ALS patients. The optical density of TDP-43+ cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.72, P < 0.01) between the immunoreactivity and duration of illness in ALS patients. Conclusions,,, These data suggest that changes of TDP-43 in ALS skin are likely to be related to the disease process and that metabolic alterations of TDP-43 may take place in the skin of patients with ALS. [source] Adipocytokines and the metabolic syndrome among older persons with and without obesity: the InCHIANTI studyCLINICAL ENDOCRINOLOGY, Issue 1 2010Sari Stenholm Summary Objectives, Adipose tissue-derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: (1) examine the role of adipocytokines in the association between obesity and the MetS and (2) to determine whether the association is different in obese and non-obese persons. Design, Cross-sectional population-based InCHIANTI study. Subjects, A total of 944 community-dwelling adults aged 65 years and older living in Tuscany, Italy. Measurements, Obesity was defined as body mass index ,30 kg/m2 and MetS as ,3 of the ATP-III criteria. Circulating levels of C-reactive protein, interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-18, tumour necrosis factor (TNF)-, R1, adiponectin, resistin and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA-IR). Results, The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA-IR, IL-1ra, TNF-, R1 and adiponectin (P < 0·05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese (P for trend 0·002) and non-obese persons (P for trend 0·001) independent of insulin resistance. Conclusions, Non-obese and obese individuals who develop an intense pro-inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation. [source] | |||||||||||||