Metabolic Factors (metabolic + factor)

Distribution by Scientific Domains


Selected Abstracts


Association between metabolic syndrome and periodontal disease

AUSTRALIAN DENTAL JOURNAL, Issue 3 2010
OM Andriankaja
Abstract Background:, Metabolic syndrome has been suggested as a potential risk factor for periodontal disease. Data based on NHANES III, with 7431 subjects aged 20 years or older, were analysed to confirm the association between metabolic syndrome and periodontal disease, and identify which components of metabolic syndrome might play a role in this association. Methods:, Clinical criteria for metabolic syndrome included: (1) abdominal obesity; (2) increased triglycerides; (3) decreased HDL cholesterol; (4) hypertension or current use of hypertension medication; and (5) high fasting plasma glucose. Periodontal disease was evaluated by probing pocket depth (PPD) and was defined as mean PPD ,2.5 mm. Results:, Women with two or more metabolic components had significantly increased odds of having periodontal disease as compared to those with no component [(two components, OR = 5.6 (95% CI: 2.2,14.4); three or more, OR = 4.7 (2.0,11.2)]. Using the definition of metabolic syndrome as having three to five metabolic components (reference group with <3 components), the adjusted odds ratios were 1.0 (0.7,1.6) for men and 2.1 (1.2,3.7) for women. Abdominal obesity was the largest contributory factor in both genders. Conclusions:, While the association between metabolic syndrome and periodontal disease was particularly significant for women, abdominal obesity appeared to be the contributing metabolic factor for both genders. [source]


RESEARCH FOCUS ON COMPULSIVE BEHAVIOUR IN ANIMALS: An animal model of compulsive food-taking behaviour

ADDICTION BIOLOGY, Issue 4 2009
Andrea Heyne
ABSTRACT The increase in the incidence of obesity and eating disorders has promoted research aimed at understanding the aetiology of abnormal eating behaviours. Apart from metabolic factors, obesity is caused by overeating. Clinical reports have led to the suggestion that some individuals may develop addictive-like behaviours when consuming palatable foods, and compulsive eating plays a similar dominant role in obesity as compulsive drug taking does in drug addiction. The progress made in the development of treatment strategies for obesity is limited, in part, because the physiological and neurological causes and consequences of compulsive eating behaviour are not clearly understood and cannot readily be studied in human subjects. We have developed experimental approaches that reflect the functioning of the components of eating control, including compulsive food taking in rats. Rats that are given free choice between standard chow and a palatable, chocolate-containing ,Cafeteria Diet' (CD) develop distinct signs of compulsive food taking that appear at an early stage. These include the inability to adapt intake behaviour in periods of limited or bitter-tasting CD access, continued food intake during resting phases and changes in fine structure of feeding (duration, distribution and recurrence of feeding bouts). The model will help examine the neurobiological underpinnings of compulsive food seeking and food taking and provides a possibility to study the effects of novel anti-obesity compounds on compulsive eating and other components of food-taking behaviour in detail. For future use of genetic models, the possibility of a transfer to a mouse was discussed. [source]


Cytosolic calcium regulates liver regeneration in the rat,

HEPATOLOGY, Issue 2 2010
Laura Lagoudakis
Liver regeneration is regulated by growth factors, cytokines, and other endocrine and metabolic factors. Calcium is important for cell division, but its role in liver regeneration is not known. The purpose of this study was to understand the effects of cytosolic calcium signals in liver growth after partial hepatectomy (PH). The gene encoding the calcium-binding protein parvalbumin (PV) targeted to the cytosol using a nuclear export sequence (NES), and using a discosoma red fluorescent protein (DsR) marker, was transfected into rat livers by injecting it, in recombinant adenovirus (Ad), into the portal vein. We performed two-thirds PH 4 days after Ad-PV-NES-DsR or Ad-DsR injection, and liver regeneration was analyzed. Calcium signals were analyzed with fura-2-acetoxymethyl ester in hepatocytes isolated from Ad-infected rats and in Ad-infected Hela cells. Also, isolated hepatocytes were infected with Ad-DsR or Ad-PV-NES-DsR and assayed for bromodeoxyuridine incorporation. Ad-PV-NES-DsR injection resulted in PV expression in the hepatocyte cytosol. Agonist-induced cytosolic calcium oscillations were attenuated in both PV-NES,expressing Hela cells and hepatocytes, as compared to DsR-expressing cells. Bromodeoxyuridine incorporation (S phase), phosphorylated histone 3 immunostaining (mitosis), and liver mass restoration after PH were all significantly delayed in PV-NES rats. Reduced cyclin expression and retinoblastoma protein phosphorylation confirmed this observation. PV-NES rats exhibited reduced c-fos induction and delayed extracellular signal-regulated kinase 1/2 phosphorylation after PH. Finally, primary PV-NES,expressing hepatocytes exhibited less proliferation and agonist-induced cyclic adenosine monophosphate responsive element binding and extracellular signal-regulated kinase 1/2 phosphorylation, as compared with control cells. Conclusion: Cytosolic calcium signals promote liver regeneration by enhancing progression of hepatocytes through the cell cycle. (HEPATOLOGY 2010;) [source]


The importance of steatosis in chronic hepatitis C infection and its management: A review

HEPATOLOGY RESEARCH, Issue 3 2010
Timothy J. S. Cross
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease with approximately 180 million people infected worldwide. Hepatic steatosis is a frequent histological finding in chronic hepatitis C (CHC) infection and is 2- to 3-fold more common than would be expected by chance alone. A high body mass index with excess visceral fat distribution is associated with steatosis in patients infected with HCV genotype 1 but not genotype 3, re-enforcing the concept that in patients with CHC, some have "metabolic steatosis", predominantly HCV genotype 1, and others "viral steatosis", mainly HCV genotype 3. Accumulating evidence suggests that steatosis may contribute to progression of fibrosis in CHC. Hepatic insulin resistance appears to play a role through the pro-fibrogenic effects of compensatory hyperinsulinemia. The aim of this review was to assess the effect host and viral factors play in steatosis development in patients with CHC infection and its possible relationship with hepatocellular carcinoma. The review examines the mechanisms by which CHC infection causes hepatic steatosis, the impact hepatic steatosis has on the natural history of the disease and finally, explores if treatments leading to a reduction in the amount of steatosis might lead to improved treatment outcomes. The basic medical science of steatosis in CHC will be discussed including proposed models of steatogenesis and the influence of viral and metabolic factors at the molecular level and how these might impact on current and future therapies. [source]


Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case,control study

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2007
Luigi Nibali
Abstract Background and Aim: A cluster of metabolic factors defines a syndrome that predisposes to diabetes and cardiovascular disease. Chronic infections such as periodontitis might alter these individual metabolic factors and the systemic inflammatory burden. The aim of this study was to investigate the association between severe periodontitis and increase in inflammatory and metabolic risk factors for cardiovascular disease. Materials and Methods: We examined 302 patients with severe periodontitis and 183 healthy controls, and we collected a blood sample from each subject in order to investigate differences in inflammatory (leukocyte numbers and differential counts) and metabolic markers (lipids and glucose). Results: After correcting for differences in age, gender, smoking and ethnicity, periodontitis subjects exhibited a low-grade systemic inflammation (increased white cell counts, 1.10±1.02 × 109/l, 95%CI 1.05,1.15, p=0.0001), dyslipidemia [lower high-density lipoprotein cholesterol, 1.14±1.03 mmol/l, 95%CI 1.08,1.20, p<0.0001 and higher low-density lipoprotein cholesterol, 1.12±1.03, 95%CI 1.05,1.19, p<0.0001) and increased non-fasting serum glucose levels (1.04±1.01 mmol/l, 95%CI 1.02,1.06, p=0.01) when compared with controls. The associations were confirmed in a subpopulation of Caucasian non-smokers. A trend for a dose dependent effect of the number of periodontal pockets on the tested inflammatory and metabolic markers was observed. Conclusions: These data suggest a possible link between severe generalized periodontitis, systemic inflammation and a dysmetabolic state in otherwise healthy individuals. [source]


Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2008
Jun-ping Shi
Abstract Background and Aims:, The clinical significance of hepatic steatosis in chronic hepatitis B infection (CHB) is unclear. The aims of this study were thus to investigate the prevalence and risk factors for hepatic steatosis in patients with CHB and its relationship with liver injury. Methods:, Consecutive patients with biopsy-proven CHB at Hangzhou Sixth People's Hospital between January 2005 and June 2007 were included. Patients co-infected with other viruses or suffering from liver disease of any other cause were excluded. Liver steatosis, necroinflammation and fibrosis were assessed by both Brunt and Scheuer classifications. Results:, A total of 1915 patients (1497 men) with a mean age of 31 ± 9.5 years were analyzed. Hepatic steatosis was present in 260 (14%) patients. The steatosis involved < 33% of hepatocytes in 90% of cases, and was more frequent among men than women (15% vs 8%, P < 0.001). Two-thirds (178 of 260) of patients with steatosis were hepatitis B e antigen (HBeAg)-positive, but there was no correlation with either serum HBeAg status or hepatitis B virus DNA titer. Degree of inflammation and fibrosis were more mild among those with steatosis than those without. Multivariate analysis showed that steatosis was independently associated with body mass index, serum triglyceride, apolipoprotein B, uric acid, and fasting blood glucose. However, fibrosis was only independently associated with age and inflammatory grade, and the latter associated with viral load and fibrosis stage. Conclusions:, Hepatic steatosis is common in CHB, it is associated with metabolic factors not viral ones, and does not appear to affect the severity of liver disease. [source]


Hepatic steatosis in chronic hepatitis B patients is associated with metabolic factors more than viral factors

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7pt1 2008
Dandan Peng
Abstract Background and Aims:, Hepatic steatosis is commonly seen in chronic hepatitis C (CHC) patients. It has been reported to be associated with both metabolic factors and viral factors, and affects the severity of fibrosis in CHC. However, the relationship between hepatic steatosis and chronic hepatitis B (CHB) is unclear. The aims of this study were to investigate the frequency of hepatic steatosis in CHB patients, to identify the factors associated with its presence, and assess the relationship between the stage of steatosis and the severity of fibrosis. Methods:, Medical records of 153 adult patients with CHB who had undergone a liver biopsy within the past 4 years were included in the study. Results:, Body mass index (BMI) and age of CHB patients with steatosis was significantly higher than the patients without steatosis (P < 0.05), as determined by the univariate analysis. Steatosis was found to correlate with the BMI values and alanine aminotransferase (ALT) levels, and ALT levels were associated with hepatitis B virus (HBV),DNA levels and histology activity index (HAI) scores, stages of fibrosis were associated with the HAI score and HBV,DNA, as determined by the multivariate analysis. In contrast, there was no significant association between advanced stages of fibrosis and steatosis. Conclusion:, Our data indicate that hepatic steatosis is more frequently present in CHB patients than in the general population. We hypothesize that steatosis in CHB patients may be due to metabolic factors and the ability of HBV to indirectly facilitate the development of steatosis. In the present study, steatosis in CHB patients was not found to be associated with the severity of fibrosis. [source]


Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2002
Jason M Hui
Abstract Background: Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. Methods: In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein,cholesterol, high-density lipoprotein,cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). Results: By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Conclusions: Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C. [source]


Evolving clinical landscape of chronic hepatitis B: A multicenter Italian study

JOURNAL OF MEDICAL VIROLOGY, Issue 12 2009
Tommaso Stroffolini
Abstract The aim of the study was to evaluate the characteristics of chronic hepatitis B with special reference to the geographical origin of the patients and to the prevalence of HBeAg and viral and non-viral co-factors of liver disease. A cross-sectional multicenter survey was undertaken, which enrolled 1,386 HBsAg chronic carriers observed consecutively in 21 referral centers over a 6-month period. The prevalence of HBeAg in patients was 11%; the presence of HBeAg was associated independently with a younger age and co-infection with HIV. Anti-HDV, anti-HCV, or anti-HIV antibodies were detected in 8.1%, 6.5%, and 2%, respectively. However, among the patients first diagnosed during the study period (incident cases), 14.3% were anti-HDV positive. Seven percent of the patients were immigrants; they were younger than Italian patients and 18% were HBeAg positive; no difference was observed in the prevalence of anti-HDV, anti-HCV, or anti-HIV antibodies. The presence of cirrhosis was associated independently with an age >52 years, the presence of anti-HDV or anti-HCV, alcohol use >4 drinks/day, and a high BMI. The clinical epidemiology of chronic hepatitis B virus (HBV) infection shows a dynamic profile, with the potential for re-emergence of cases with HBeAg or anti-HDV and an emerging impact of metabolic factors on the evolution of liver disease. J. Med. Virol. 81:1999,2006, 2009. © 2009 Wiley-Liss, Inc. [source]


Effect of oral melatonin on the procoagulant response to acute psychosocial stress in healthy men: a randomized placebo-controlled study

JOURNAL OF PINEAL RESEARCH, Issue 4 2008
Petra H. Wirtz
Abstract:, Acute mental stress is a potent trigger of acute coronary syndromes. Catecholamine-induced hypercoagulability with acute stress contributes to thrombus growth after coronary plaque rupture. Melatonin may diminish catecholamine activity. We hypothesized that melatonin mitigates the acute procoagulant stress response and that this effect is accompanied by a decrease in the stress-induced catecholamine surge. Forty-five healthy young men received a single oral dose of either 3 mg melatonin (n = 24) or placebo medication (n = 21). One hour thereafter, they underwent a standardized short-term psychosocial stressor. Plasma levels of clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, and catecholamines were measured at rest, immediately after stress, and 20 min and 60 min post-stress. The integrated change in D-dimer levels from rest to 60 min post-stress differed between medication groups controlling for demographic and metabolic factors (P = 0.047, = 0.195). Compared with the melatonin group, the placebo group showed a greater increase in absolute D-dimer levels from rest to immediately post-stress (P = 0.13; = 0.060) and significant recovery of D-dimer levels from immediately post-stress to 60 min thereafter (P = 0.007; = 0.174). Stress-induced changes in FVII:C, FVIII:C, fibrinogen, and catecholamines did not significantly differ between groups. Oral melatonin attenuated the stress-induced elevation in the sensitive coagulation activation marker D-dimer without affecting catecholamine activity. The finding provides preliminary support for a protective effect of melatonin in reducing the atherothrombotic risk with acute mental stress. [source]


Suppression of Heavy Drinking and Alcohol Seeking by a Selective ALDH-2 Inhibitor

ALCOHOLISM, Issue 11 2009
Maria P. Arolfo
Background:, Inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH-2 inhibitor might affect other metabolic factors involved in regulating drinking. Methods:, Aldehyde dehydrogenase 2 inhibitors were synthesized based on the co-crystal structure of ALDH-2 and daidzin. We tested the efficacy of a highly selective reversible ALDH-2 inhibitor, CVT-10216, in models of moderate and high alcohol drinking rats. We studied 2-bottle choice and deprivation-induced drinking paradigms in Fawn Hooded (FH) rats, operant self-administration in Long Evans (LE), FH, and inbred P (iP) rats and in cue-induced reinstatement in iP rats. We also assayed blood acetaldehyde levels as well as dopamine (DA) release in the nucleus accumbens (NAc) and tested possible rewarding/aversive effects of the inhibitor in a conditioned place preference (CPP) paradigm. Results:, CVT-10216 increases acetaldehyde after alcohol gavage and inhibits 2-bottle choice alcohol intake in heavy drinking rodents, including deprivation-induced drinking. Moreover, CVT-10216 also prevents operant self-administration and eliminates cue-induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT-10216 prevents alcohol-induced increases in NAc DA without changing basal levels. CVT-10216 does not show rewarding or aversive properties in the CPP paradigm at therapeutic doses. Conclusion:, Our findings suggest that selective reversible ALDH-2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics. [source]


A Review of Genetic, Biological, Pharmacological, and Clinical Factors That Affect Carbohydrate-Deficient Transferrin Levels

ALCOHOLISM, Issue 9 2004
Michael F. Fleming
Background: Carbohydrate-deficient transferrin (CDT) is an alcohol biomarker recently approved by the U.S. Food and Drug Administration. This test is increasingly being used to detect and monitor alcohol use in a variety of health care, legal, and industrial settings. The goal of this study is to review the genetic, biological, pharmacological, and clinical factors that may affect CDT levels. Methods: A review of the literature identified 95 research articles that met the authors' criteria and reported potential interactions of a variety of factors on percent and total CDT levels. The review established 12 categories of variables that may affect CDT levels. These categories include (1) alcohol use, (2) genetic factors, (3) race, (4) gender, (5) age, (6) liver disease, (7) iron levels, (8) tobacco use, (9) medication such as estrogen and anticonvulsants, (10) metabolic factors such as body mass index and total body water, (11) chronic medical conditions such as rheumatoid arthritis, and (12) surgical patients. Results: There is evidence that %CDT levels are affected by alcohol use, end-stage liver disease, and genetic variants. In addition to these three factors, total CDT levels (CDTect) are also affected by factors that raise transferrin levels such as iron deficiency, chronic illnesses, and menopausal status. Other potential factors such as tobacco and age appear to be confounded by alcohol use. The roles of female gender, low body mass index, chronic inflammatory diseases, and medication on CDT levels require further study. False negatives are associated with female gender, episodic lower level alcohol use, and acute trauma with blood loss. Conclusions: This review suggests that a number of factors are associated with false-positive CDTect and %CDT levels. CDT offers great promise to assist physicians in the care of patients to detect and monitor heavy alcohol use. [source]


Electrophysiological findings of peripheral neuropathy in newly diagnosed type II diabetes mellitus

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2005
Eugenia Rota
Abstract This study was aimed at assessing the electrophysiological signs of peripheral neuropathy in diabetes mellitus (DM) type II patients at diagnosis. Nerve conduction studies (NCS) of median, ulnar, peroneal, tibial and sural nerves were performed in 39 newly diagnosed DM subjects and compared to those of 40 healthy controls. Metabolic indices were also investigated. Electrophysiological alterations were found in 32 (82%) of the DM patients, and more than half of them (62.2%) showed multiple (two to five) abnormal parameters. Because most of the subjects (84.4%) had from two to five nerves involved, these alterations were widespread in the seven nerves evaluated. Forty-two percent of the patients had NCS alterations suggestive of distal median mononeuropathy, implying that metabolic factors in DM make the median nerve more susceptible to focal entrapment. A reduced sensory nerve action potential (SNAP) amplitude was observed in the median nerve in 70% of the patients, in the ulnar in 69% and in the sural nerve only in 22%. In the presence of a decrease in the SNAP amplitude of the ulnar or median nerve, the SNAP amplitude of the sural nerve was normal in 82 or 80% of the subjects, respectively. This finding may be in keeping with a distal involvement of the sensory fibres, as explored by routine median or ulnar NCS. No correlation was found between metabolic indices and NCS parameters. In conclusion, a high percentage of newly diagnosed DM patients show signs of neuropathy, and upper limb nerve sensory NCS seem to be more sensitive in detecting it than lower limb NCS. [source]


Physical activity, sport, and pediatric diabetes

PEDIATRIC DIABETES, Issue 1 2006
MC Riddell
Abstract:, The benefits derived from regular physical activity include improved cardiovascular fitness, increased lean mass, improved blood lipid profile, enhanced psychosocial well-being, and decreased body adiposity. The benefits for children with diabetes may also include blood glucose control and enhanced insulin sensitivity. However, for these children, engagement in vigorous physical activity and sport must be properly controlled through modifications in insulin therapy and nutritional intake so that the benefits of exercise outweigh the risks. The following review describes the various physiological and metabolic factors which occur both during exercise and during sport while describing specific recommendations to control glucose excursions by proper insulin management and diet. [source]


Evidence for the Influence of Diet on Cranial Form and Robusticity

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2010
Rachel A. Menegaz
Abstract The evolutionary significance of cranial form and robusticity in early Homo has been variously attributed to allometry, encephalization, metabolic factors, locomotor activity, and masticatory forces. However, the influence of such factors is variably understood. To evaluate the effect of masticatory loading on neurocranial form, sibling groups of weanling white rabbits were divided into two cohorts of 10 individuals each and raised on either a soft diet or a hard/tough diet for 16 weeks until subadulthood. Micro-CT was used to quantify and visualize morphological variation between treatment groups. Results reveal trends (P < 0.10) for greater outer table thickness of the frontal bones, zygomatic height, and cranial globularity in rabbits raised on a hard/tough diet. Furthermore, analyses of three-dimensional coordinate landmark data indicate that the basicrania of hard/tough diet rabbits exhibit more robust middle cranial fossae and pterygoid plates, as well as altered overall morphology of the caudal cranial fossa. Thus, long term increases in masticatory loads may result in thickening of the bones of the neurocranial vault and/or altering the curvature of the walls. Differences in cranial regions not directly associated with the generation or resistance of masticatory forces (i.e., frontal bone, basicranium) may be indirectly correlated with diet-induced variation in maxillomandibular morphology. These findings also suggest that long-term variation in masticatory forces associated with differences in dietary properties can contribute to the complex and multifactorial development of neurocranial morphology. Anat Rec, 293:630,641, 2010. © 2010 Wiley-Liss, Inc. [source]


Molecular anatomy of a speckle

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2006
Lisa L. Hall
Abstract Direct localization of specific genes, RNAs, and proteins has allowed the dissection of individual nuclear speckles in relation to the molecular biology of gene expression. Nuclear speckles (aka SC35 domains) are essentially ubiquitous structures enriched for most pre-mRNA metabolic factors, yet their relationship to gene expression has been poorly understood. Analyses of specific genes and their spliced or mature mRNA strongly support that SC35 domains are hubs of activity, not stores of inert factors detached from gene expression. We propose that SC35 domains are hubs that spatially link expression of specific pre-mRNAs to rapid recycling of copious RNA metabolic complexes, thereby facilitating expression of many highly active genes. In addition to increasing the efficiency of each step, sequential steps in gene expression are structurally integrated at each SC35 domain, consistent with other evidence that the biochemical machineries for transcription, splicing, and mRNA export are coupled. Transcription and splicing are subcompartmentalized at the periphery, with largely spliced mRNA entering the domain prior to export. In addition, new findings presented here begin to illuminate the structural underpinnings of a speckle by defining specific perturbations of phosphorylation that promote disassembly or assembly of an SC35 domain in relation to other components. Results thus far are consistent with the SC35 spliceosome assembly factor as an integral structural component. Conditions that disperse SC35 also disperse poly(A) RNA, whereas the splicing factor ASF/SF2 can be dispersed under conditions in which SC35 or SRm300 remain as intact components of a core domain. Anat Rec Part A, 288A:664,675, 2006. © 2006 Wiley-Liss, Inc. [source]


Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with neural tube defects in southern Brazil,

BIRTH DEFECTS RESEARCH, Issue 7 2004
Têmis Maria Félix
Abstract BACKGROUND The importance of metabolic factors in neural tube defects (NTDs) has been the focus of many investigations. Several authors have suggested that abnormalities in homocysteine metabolism, such as hyperhomocysteinemia, folate deficiency, and low vitamin B12, may be responsible for these malformations and that both nutritional factors and genetic abnormalities are associated with them. METHODS We conducted a case-control study to investigate the influence of biochemical and genetic factors in NTDs in infants in southern Brazil. Levels of folate, vitamin B12, total homocysteine (t-Hcy) and the 677C>T and 1298A>C polymorphisms of the MTHFR gene were analyzed in 41 NTD child,mother pairs and 44 normal child,mother control pairs. RESULTS Subjects in the case group had a higher mean blood folate level than those in the control group. The level of vitamin B12 was lower in mothers in the NTD group than in control mothers (p = 0.004). The level of t-Hcy was not different in the two groups, but t-Hcy and vitamin B12 were correlated (p = 0.002). There was no difference in the genotype distribution for 677C>T and 1298A>C polymorphisms of MTHFR in the case and control pairs. The level of t-Hcy was correlated with 677TT. CONCLUSIONS Despite the small sample in this study, we suggest that low vitamin B12 and, consequently, hyperhomocysteinemia are important risk factors for NTDs in our population. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source]


Review article: The impact of obesity on reproduction in women with polycystic ovary syndrome

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2006
R 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]


2221: Gases and the ocular vasculature

ACTA OPHTHALMOLOGICA, Issue 2010
L SCHMETTERER
Purpose The regulation of ocular blood flow and oxygenation is largely controlled by metabolic factors. Among them gases like oxygen (O2), carbon dioxide (CO2), carbon monoxide (CO) and nitroc oxide (NO) play a key role. Methods In a series of clinical trials we focussed on the role of O2, CO2, CO and NO in the control of ocular blood flow. These studies were done on healthy subjects and employed a number of techniques including laser Doppler flowmetry, color Doppler imaging and pulsatile ocular blood flow techniques. Results O2 is a very potent vasoconstrictor in the retina and optic nerve head, but not in the choroid. The mechanisms underlying this effect is not entirely clear, but appears to involve endothelin A receptors. CO and CO2 are potent vasodilators in retina, choroid and optic nerve head. NO plays a major role in the control of basal vascular tone in all ocular vessels, but is also involved in many agonist-induced vasodilator effects. Conclusion Gases play a key role in controlling ocular blood flow. An imblanace of the production of these mediators is associated with ischemia, hypoxia and endothelial dysfunction. [source]