Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor beta-1 is involved in local signaling for a variety of human diseases including renal diseases, cardiac hypertrophy and fibrosis in heart failure, hepatic fibrosis, and pulmonary fibrosis. Elevated levels of circulating transforming growth factor beta-1 result in organ fibrosis in animal models. In humans smoking, hypertension, diabetes and obesity appear to result in elevated circulating levels. This paper outlines a hypothesis that elevated circulating levels of transforming growth factor beta-1 are part of the molecular link between several entities that have epidemiologic ties including hypertension, diabetes, smoking and obesity on one hand and diseases resulting in organ fibrosis on the other including renal disease and cardiac fibrosis and hypertrophy in heart failure. Additionally, it is suggested that elevated levels are not simply a marker of a similar mechanism of disease production but that elevated levels of circulating transforming growth factor beta-1 lead to disease production and to the synergy of risk factors seen in production of human fibrotic diseases.
Med Sci Monit 2005 Jul
PMID:Circulating transforming growth factor beta-1: a partial molecular explanation for associations between hypertension, diabetes, obesity, smoking and human disease involving fibrosis. 1612 68

Glucagon-like peptide-1 (GLP-1) is produced both in the human and rat intestine and brain. The release of GLP-1 into the blood is mediated by factors of neural and hormonal origin and is stimulated by the presence of nutrients in the digestive tract, while the enzyme dipeptidyl peptidase IV and the kidneys are responsible for, respectively, the rapid degradation and excretion of the hormone. Peripherally secreted GLP-1 enhances insulin synthesis and release and maintains the normal anatomical status of pancreatic islets. Diminished GLP-1 response to ingested food, associated with attenuated insulin release and glucose intolerance, was found in non-insulin-dependent diabetes mellitus. GLP-1 replacement in diabetic subjects normalized these parameters, thus indicating a role for this peptide in the pathogenesis of type 2 diabetes. GLP-1 might also be involved in the pathophysiology of obesity and stress to some extent. Both peripheral and central GLP-1 are probably involved in the control of feeding centers as an anorexic agent. GLP-1 affects the activity of the hypothalamo-pituitary-adrenal axis both under basal and stress conditions, including taste aversion learning. Hence, GLP-1-dependent pathophysiological mechanisms may participate in the pathogenesis of the most common metabolic and behavioral disorders.
Med Sci Monit 2005 Aug
PMID:Physiology and pathophysiology of glucagon-like peptide-1 (GLP-1): the role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress. 1604 95

The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes; 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method. A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0.1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 kg (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, eg, effects on neonatal obesity and insulin resistance, remain unknown.
Ther Drug Monit 2006 Feb
PMID:Population pharmacokinetics of metformin in late pregnancy. 1641 96

A body of evidence indicates that masked hypertension is a significant predictor of cardiovascular disease, but how to identify these patients is still a matter of dispute. Data obtained in several cross-sectional studies have demonstrated that masked hypertension is associated with increased left ventricular mass index and carotid intima-media thickness, and impaired large artery distensibility. Furthermore, in longitudinal studies, masked hypertension was a strong predictor of cardiovascular morbidity and mortality. Several factors that can selectively raise ambulatory blood pressure increase the likelihood of having masked hypertension. These include younger age, smoking, alcohol use, contraceptive use in women, sedentary habits and central obesity. In addition, masked hypertension is more common in individuals with high-normal clinic blood pressure or transiently elevated blood pressure. Increased reactivity to daily life stressors and behavioural factors are other important predictors of masked hypertension. In clinical practice, masked hypertension should be searched for in individuals who are more likely to have this condition or are at increased risk of cardiovascular events including those with coronary, cerebrovascular or kidney disease, patients with diabetes and individuals with a high cardiovascular risk profile. To determine whether the use of ambulatory blood pressure monitoring is cost-effective in these individuals, further research is needed.
Blood Press Monit 2005 Dec
PMID:Masked hypertension in adults. 1649 45

Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa, and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its action on glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhanced TNF-alpha production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassium regimen in these clinical conditions, sepsis, and cancer.
Med Sci Monit 2006 May
PMID:Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. 1664 87

Recent studies suggest that adipose tissue hormones ("adipokines") are involved in the pathogenesis of various complications of obesity, including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Apelin and visfatin are two recently described adipokines, although they are also synthesized outside adipose tissue. Apelin exists in at least three forms, consisting of 13, 17, or 36 amino acids, all originating from a common 77-amino-acid precursor. In the cardiovascular system, apelin elicits endothelium-dependent, nitric oxide-mediated vasorelaxation and reduces arterial blood pressure. In addition, apelin demonstrates potent and long-lasting positive inotropic activity which is preserved even in injured myocardium and is not accompanied by myocardial hypertrophy. Apelin synthesis in adipocytes is stimulated by insulin, and plasma apelin level markedly increases in obesity associated with insulin resistance and hyperinsulinemia. In addition to regulating cardiovascular function, apelin inhibits water intake and vasopressin production. Visfatin, previously recognized as a pre-B cell colony-enhancing factor (PBEF), is abundantly expressed in visceral adipose tissue and is upregulated in some, but not all, animal models of obesity. Preliminary studies suggest that plasma visfatin concentration is also increased in humans with abdominal obesity and/or type 2 diabetes mellitus. Visfatin binds to the insulin receptor at a site distinct from insulin and exerts hypoglycemic effect by reducing glucose release from hepatocytes and stimulating glucose utilization in peripheral tissues. Thus, apelin and visfatin are unique among adipose tissue hormones in that they are upregulated in the obese state and both exert primarily beneficial effects.
Med Sci Monit 2006 Jun
PMID:Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? 1694 Sep 39

The purpose of the work was to investigate the influence of psychosocial factors on the development of ischemic heart disease and arterial hypertension in persons with genetic predisposition to cardiovascular disease. Three groups of patients were investigated: 72 patients with AH, 175 patients with IHD (74 with angina pectoris and 101 with angina pectoris and myocardial infarction) and 164 patients with IHD and AH. In nearest relation of 283 (69/03%) patients from 410 were found the presence of high arterial hypertension, myocardial infarction, diabetes and obesity. In this persons reliable relationship were found between psychosocial and genetic factors (in persons with genetic predisposition to cardiovascular disease were found high rate of anxiety, frequent stressful situations at work and in family, psychoemotional overloads). On the basis of our investigations it may be concluded that the genetic and psychosocial factors together play important role in the development of IHD and AH, that perhaps caused from influence of genetic factors on capable of to overcome the stress.
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PMID:[The influence of psychosocial factors in developments of ischemic heart disease and arterial hypertension in persons with genetic predisposition]. 1690 44

In the UK the mental and physical health and well-being of millions of women are influenced by living in poverty. Low educational attainment, unemployment, low pay and poor areas of residence exacerbate the challenges of obtaining optimal food choices, dietary intake and healthy eating patterns. Poorer women are more likely to eat low amounts of fruits and vegetables, whole grains and fish, and higher amounts of sugar and sweetened drinks compared with more affluent women. Diet contributes to the health inequalities evident in high rates of diet-related morbidity (including obesity) and mortality (including IHD and stroke) and in maternal and child health considerations (including breast-feeding and family diet practices). There is a dearth of research on effective interventions undertaken with low-income women, reflecting some of the challenges of engaging and evaluating programmes with this 'hard to reach' subpopulation. Intervention programmes from the USA, including WISEWOMAN, the Women's Health Initiative, the American Special Supplemental Food Program for Women, Infants and Children and the Expanded Food and Nutrition Education Program provide models for changing behaviour amongst women in the UK, although overall effects of such programmes are fairly modest. Lack of evidence does not mean that that policy work should be not be undertaken, but it is essential that policy work should be evaluated for its ability to engage with target groups as well as for the behavioural change and health outcomes.
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PMID:Nutrition interventions in women in low-income groups in the UK. 1734 69

We report the concentrations of scheduled prescription drugs in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID). The investigation covered a 2 year period 2004 (N = 7052 cases) and 2005 (N = 7759 cases) and was prompted by recent legislation stipulating zero-concentration limits in blood for controlled substances. However, prescription drugs are exempt from the zero-limit law provided that the medication was being used in accordance with a doctor's prescription. The blood concentrations of various psychoactive substances were compared with the limits of quantitation of the analytic method used and the so-called therapeutic concentration range according to various reference books and tabulations. Diazepam [N = 1950 (26%)] and nordazepam [N = 2168 (28%)] were the therapeutic agents most frequently identified in these forensic blood samples along with other benzodiazepines such as alprazolam [N = 430 (5.6%)], flunitrazepam [N = 308 (4.0%)], and nitrazepam [N = 222 (2.9%)]. The newer hypnotics, exemplified by zolpidem [N = 148 (1.9%)] and zopiclone [N = 111 (1.5%)], were also high on the list of psychoactive substances identified. Interpreting the concentration of a prescription drug in blood in relation to whether the person had taken an overdose or was abusing the substance in question is not always easy. The age, gender, degree of obesity, and ethnicity of the person concerned; the pharmacokinetic profile of the drug; polymorphism of drug-metabolizing enzymes as well as liver and kidney function and blood hematocrit need to be considered. Among preanalytic factors, stability of the drug in blood after sampling, the type of tubes and preservatives used, the dosage form and route of administration deserve consideration. When therapeutic drug monitoring concentrations are compared with forensic toxicology results, then the plasma-to-whole blood distribution ratio of the drug also needs to be considered. In blood samples from DUID suspects, the concentrations of many commonly used sedatives and hypnotics exceeded the accepted therapeutic limits, which gives an indication of the abuse potential of these types of medications.
Ther Drug Monit 2007 Apr
PMID:Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results. 1741 81

Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.
Med Sci Monit 2007 Dec
PMID:Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. 1804 45


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