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PubMed1999

Mechanisms for hyperglycemia in the metabolic syndrome. The key role of beta-cell dysfunction.

Hyperglycemia in Type 2 diabetes represents a steady-state re-regulation of plasma glucose to a higher-than-normal level after an overnight fast. The underlying pathophysiology represents an interaction between impaired beta-cell function and peripheral and hepatic insulin resistance which leads to abnormal hepatic glucose production. Subjects with the Metabolic Syndrome are at an increased risk for Type 2 diabetes and often have one or both of these disorders present even when glucose tolerance is normal. Thus, sophisticated measures of beta-cell function and insulin sensitivity demonstrate a high frequency in populations characterized as having a high prevalence of atherosclerosis, central obesity, hypertension, and dyslipidemia with or without impaired glucose tolerance. Hyperglycemia compensates for the impairment of beta-cell function and therefore, in our view, the beta-cell is the critical factor in its development. Hyperinsulinemia, a curvilinear compensation for insulin resistance that is closely correlated with central adiposity, is another important predictor of hyperglycemia. In a Japanese-American population followed for five years, impaired beta-cell function was present at baseline and preceded the accumulation of intraabdominal fat in those who developed Type 2 diabetes five years later. This interaction between these two pathophysiologic abnormalities in this sequence supports the hypothesis that beta-cell dysfunction contributes to the development of central adiposity by reduced CNS insulin signaling.

Diabetes Mellitus, Type 2↗

PubMed2000

Hypothalamic-pituitary-adrenal dysfunction in Apoe(-/-) mice: possible role in behavioral and metabolic alterations.

Several neurological diseases are frequently accompanied by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis regulates the secretion of glucocorticoids (GCs), which play important roles in diverse brain functions, including cognition, emotion, and feeding. Under physiological conditions, GCs are adaptive and beneficial; however, prolonged elevations in GC levels may contribute to neurodegeneration and brain dysfunction. In the current study, we demonstrate that apolipoprotein E (apoE) deficiency results in age-dependent dysregulation of the HPA axis through a mechanism affecting primarily the adrenal gland. Apoe(-/-) mice, which develop neurodegenerative alterations as they age, had an age-dependent increase in basal adrenal corticosterone content and abnormally increased plasma corticosterone levels after restraint stress, whereas their plasma and pituitary adrenocorticotropin levels were either unchanged or lower than those in controls. HPA axis dysregulation was associated with behavioral and metabolic alterations. When anxiety levels were assessed in the elevated plus maze, Apoe(-/-) mice showed more anxiety than wild-type controls. Apoe(-/-) mice also showed reduced activity in the open field. Finally, Apoe(-/-) mice showed age-dependent increases in food and water intake, stomach and body weights, and decreases in brown and white adipose tissues. These results support a key role for apoE in the tonic inhibition of steroidogenesis and HPA axis activity and have important implications for the behavioral analysis of Apoe(-/-) mice.

Adrenal Glands↗

PubMed2007

beta-Secretase expression in normal and functionally deprived rat olfactory bulbs: inverse correlation with oxidative metabolic activity.

Cerebral hypometabolism, mitochondrial dysfunction, and beta-amyloid peptide (Abeta) accumulation are well-characterized manifestations of Alzheimer's disease (AD). beta-Secretase (BACE) is a prerequisite for amyloidogenesis, and it is up-regulated in sporadic AD. To explore a potential in vivo mechanism by which Abeta production is modulated by neuronal activity and/or oxidative metabolism, we compared BACE expression with cytochrome c oxidase (CO) or succinic dehydrogenase (SDH) activity in normal and functionally deprived adult rat olfactory bulb. In normal bulb, BACE was expressed predominantly in the glomerular layer, but labeling intensity within individual glomeruli varied substantially. A strong negative correlation existed between BACE labeling intensity and CO or SDH activity among individual glomeruli. Unilateral naris occlusion resulted in elevated glomerular BACE labeling in the deprived bulbs relative to the nondeprived counterparts, which was correlated with decreased CO activity in the same anatomic location. Enhanced BACE labeling was confirmed by measurements of elevated protein levels, enzymatic activity, and beta-site cleavage products of amyloid precursor protein in bulb extracts. Our findings reveal a negative regulation of BACE expression by physiological neuronal activity and an intrinsic inverse correlation between BACE expression and oxidative metabolism at the first synapse on the olfactory pathway. The results point to a biological role of BACE in synapse function and plasticity as well as a potential mechanism whereby reduced neuronal activity or metabolism could lead to amyloid overproduction in synaptic terminals.

Amyloid Precursor Protein Secretases↗

PubMed1997

Endothelial dysfunction: cause of the insulin resistance syndrome.

Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the "insulin resistance syndrome," according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the well-established and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.

Animals↗

PubMed1999

Magnetic resonance proton spectroscopy of the brain in Wilson's disease.

We studied 13 patients with Wilson's disease (WD) using localized magnetic resonance proton spectroscopy to test whether hepatic encephalopathy or impaired energy metabolism contributes to neurological dysfunction. Levels of myoinositol (MI), choline-containing compounds (Cho), creatine (Cr), N-acetyl-aspartate (NAA), Glx (unresolved resonances of glutamate, glutamine, and gamma-aminobutyric acid) and lactate were measured using a relative quantitative approach. Results were compared with those from 12 healthy controls. In one patient with de novo WD and acute hepatic disease but no neurological symptoms we found a marked decrease in the Cho/Cr and MI/Cr ratios. However, proton spectroscopy in the white matter, gray matter, and putamen of patients with treated WD showed no significant differences compared to healthy controls. In none of the subjects studied was the lactate/Cr ratio elevated. The spectroscopic findings were compatible with subclinical hepatic encephalopathy in the one patient with de novo WD and acute hepatic disease, but this does not play a major role in brain dysfunction in patients with treated WD. Additionally, there was no evidence of increased lactate concentration, indicating that cerebral energy metabolism was not grossly impaired.

Adolescent↗

PubMed1999

Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients with type I diabetes mellitus under good metabolic control.

Dyspnoea and pulmonary dysfunction have recently been associated with Type I (insulin-dependent) diabetes mellitus. The putative role of altered pulmonary mechanics and of performance of inspiratory muscles in inducing dyspnoea has not been yet assessed in Type I diabetes. To better focus on this topic we evaluated nine patients with Type I diabetes mellitus, aged 19 to 48 years with good and stable metabolic control, without a history of smoking and microvascular complications, alongside a group of 14 healthy control subjects. In each subject, pulmonary volumes, static and dynamic compliance, pleural pressure swings (Pplsw), maximal inspiratory pressures (Pplsn), Pplsw(%Pplsn), a measure of respiratory muscle effort, and tension-time index [TTI=TI/TTOTxPplsw(%Pplsn)] were measured (TI=inspiratory time;TTOT=total time of the respiratory cycle). All subjects were studied at baseline and during hypoxic rebreathing. Patients had normal pulmonary volumes. During hypoxic rebreathing, a normal change in respiratory muscle effort [DeltaPplsw(%Pplsn)/DeltaSaO2] and DeltaTTI/DeltaSaO2, and a lower change in tidal volume versus change in oxygen saturation [DeltaVT(% vital capacity)/DeltaSaO2], resulted in a higher ratio of respiratory effort to tidal volume [Pplsw(%Pplsn)/VT(% vital capacity)], a measure of neuroventilatory dissociation of the respiratory pump. Hypoxic dyspnoea, assessed by a modified Borg scale, showed a greater rate of rise (DeltaBorg/DeltaSaO2) and a greater increase for a given level of respiratory effort in patients. Moreover, neuroventilatory dissociation related to the expression of peripheral airway involvement, as assessed in terms of low dynamic compliance, and to concurrent change in dyspnoea sensation. Patients with Type I diabetes mellitus under good metabolic control and with normal lung volumes may have abnormal peripheral airway function. The latter is thought to be responsible for the association between dyspnoea sensation and neuroventilatory dissociation.

Adult↗

PubMed1992

Endocrine dysfunction in Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction. Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperaldosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroidism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroidism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroidism was found.

Child↗

PubMed2004

Metabolic consequences of hypoxia from birth and dexamethasone treatment in the neonatal rat: comprehensive hepatic lipid and fatty acid profiling.

Neonatal hypoxia is a common condition resulting from pulmonary and/or cardiac dysfunction. Dexamethasone therapy is a common treatment for many causes of neonatal distress, including hypoxia. The present study examined the effects of dexamethasone treatment on both normoxic and hypoxic neonatal rats. We performed comprehensive hepatic fatty acid/lipid profiling and evaluated changes in pertinent plasma hormones and lipids and a functional hepatic correlate, i.e. hepatic lipase activity. Rats were exposed to hypoxia from birth to 7 d of age. A 4-d tapering dose regimen of dexamethasone was administered on: postnatal day (PD)3 (0.5 mg/kg), PD4 (0.25 mg/kg), PD5 (0.125 mg/kg), and PD6 (0.05 mg/kg). The most significant finding was that dexamethasone attenuated nearly all hypoxia-induced changes in hepatic lipid profiles. Hypoxia increased the concentration of hepatic triacylglyceride and free fatty acids and, more specifically, increased a number of fatty acid metabolites within these lipid classes. Administration of dexamethasone blocked these increases. Hypoxia alone increased the plasma concentration of cholesterol and triacylglyceride, had no effect on plasma glucose, and only tended to increase plasma insulin. Dexamethasone administration to hypoxic pups resulted in an additional increase in plasma lipid concentrations, an increase in insulin, and a decrease in plasma glucose. Hypoxia and dexamethasone treatment each decreased total hepatic lipase activity. Normoxic pups treated with dexamethasone displayed increased plasma lipids and insulin. The effects of dexamethasone on hepatic function in the hypoxic neonate are dramatic and have significant implications in the assessment and treatment of metabolic dysfunction in the newborn.

Animals↗

PubMed2003

Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease.

Obesity, insulin resistance, and endothelial dysfunction closely coexist throughout the natural history of type 2 diabetes. They all can be identified not only in people with type 2 diabetes, but also in various groups at risk for the disease, such as individuals with impaired glucose tolerance, family history of type 2 diabetes, hypertension, dyslipidemia, prior gestational diabetes, or polycystic ovary syndrome. Whereas their evident association cannot fully establish a cause-effect relationship, fascinating mechanisms that bring them closer together than ever before are rapidly emerging. Central or abdominal obesity leads to insulin resistance and endothelial dysfunction through fat-derived metabolic products, hormones, and cytokines. Insulin resistance leads to endothelial dysfunction through the frequent association with traditional cardiovascular risk factors and through some more direct novel mechanisms. Some specific and shared insulin signaling abnormalities in muscle, fat, and endothelial cells, as well as some new genetic and nontraditional factors, may contribute to this interesting association. Some recent clinical studies demonstrate that nonpharmacological and pharmacological strategies targeting obesity and/or insulin resistance ameliorate endothelial function and low-grade inflammation. All these findings have added a new dimension to the association of obesity, insulin resistance, and endothelial dysfunction that may become a key target in the prevention of type 2 diabetes and cardiovascular disease.

Diabetes Mellitus, Type 2↗

PubMedDate not supplied

[Vascular headache, thrombopenia and serotonin metabolism].

The role of platelet serotonin in migraine remains a subject of controversy. However, the frequency of association of migraine with antibody-mediated thrombocytopenia would suggest that platelet dysfunction or impaired serotonin metabolism might play a role in migrainous attack. We report three new cases, two involving chronic idiopathic thrombocytopenia and one lupus. The observation of high levels of anti-platelet antibodies in close correlation with the occurrence of attacks suggests that the Serotonin Releasing Factor (SRF) could be concerned. This was suspected previously on the basis of in vitro studies. The hypothesis that other forms of migraine might be linked to an immunopathological process involving other immunoglobulins is proposed (Acta neurol. belg., 1988, 88, 290-296).

Adult↗

PubMed2005

Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction.

INTRODUCTION: Advanced age in men is accompanied by an increased prevalence of cardiovascular disease (CVD) and erectile dysfunction (ED). Prior studies revealed that 56% of an ED population have asymptomatic myocardial ischemia, 75% of men with CAD have symptoms of ED, and 91% of our ED patients have cardiovascular risks. AIM: Because metabolic syndrome (MS) and insulin resistance (IR) are both predictors of CVD, we wished to evaluate these parameters in our population. METHODS: Our men (N = 154) were evaluated for multiple cardiovascular risk factors and graded on severity of ED. The severity of ED was evaluated by the Sexual Health Inventory for Men (SHIM) questionnaire. The prevalence of MS was determined by NCEP/ATP III criteria. Insulin resistance was measured by QUICKI. MAIN OUTCOME MEASURES: Bivariate associations among total cholesterol/high-density lipoprotein (HDL), triglyceride/HDL, and Quantitative Insulin Sensitivity Check Index (QUICKI) were compared. Chi-square analysis was used to evaluate the relation between the presence and severity of IR with the severity of ED. RESULTS: The total cholesterol/HDL ratio was moderately and negatively correlated with QUICKI (r = -0.33; P < 0.01) and similarly for the triglyceride/HDL ratio (r = -0.32; P < 0.01). Metabolic syndrome was present in 43% of our ED population as opposed to 24% in a matched patient population. Approximately 79.2% of our total population had IR and 73.3% of the nondiabetic portion (N = 120) had IR, compared to 26% in a general population study. Metabolic syndrome (P = 0.01), IR (P = 0.01), and fasting blood sugar (FBS) >110 mg/dL (P = 0.01) correlated positively and moderately with increasing severity of ED by SHIM score. CONCLUSION: Men with ED have a high incidence of MS and IR. Early detection of metabolic disease in patients with ED may be a gateway to the reduction endothelial dysfunction in younger men with increased cardiovascular risk but who present for treatment of ED alone.

Comorbidity↗

PubMed1992

Dependence of recovery of contractile function on maintenance of oxidative metabolism after myocardial infarction.

This study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of the potential for functional recovery after revascularization in patients with recent myocardial infarction. In 11 patients (mean interval after infarction 6 days; 5 patients given thrombolytic therapy), positron emission tomography (PET) was performed to characterize myocardial perfusion (with oxygen-15-labeled water), glucose utilization (with fluorine-18-fluorodeoxyglucose) and oxidative metabolism (with carbon-11-acetate). Dysfunctional but viable myocardium was differentiated from nonviable myocardium by assessments of regional function before and after coronary revascularization. The impact of coronary revascularization on regional myocardial perfusion and metabolism was assessed in nine patients in whom tomography was repeated after revascularization. Before revascularization, dysfunctional but viable myocardium (19 segments) and nonviable myocardium (10 segments) exhibited relative perfusion equivalent to 74% and 63% of that of normal myocardium (33 segments), respectively (p less than 0.02). Dysfunctional but viable myocardium exhibited oxidative metabolism equivalent to 74% of that of normal myocardium (p less than 0.02). In contrast, in nonviable myocardium, oxidative metabolism was only 45% of that seen in normal (p less than 0.02) and 60% of that in reversibly dysfunctional myocardium (p less than 0.003). Regional glucose utilization (normalized to regional perfusion) in dysfunctional but viable myocardium was higher than that in normal myocardium (p less than 0.02). Nonviable myocardium exhibited lower levels of glucose utilization than did normal tissue (p less than 0.02). However, in both reversibly and persistently dysfunctional myocardium utilization of glucose normalized to relative perfusion was markedly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Energy metabolism in myocardial stunning.

We investigated the effect of reversible ischemia, leading to persistent contractile dysfunction (stunning), on myocardial energy metabolism. The balance of energy metabolism is expressed by the phosphorylation state of cytosolic nucleotides. This variable cannot be measured directly because of nucleotide compartmentation, but in the isolated heart it can be estimated by the release of purine catabolites. We have previously shown that increased energy consumption or impaired energy production cause purine release to increase, while primary reduction in energy consumption has the opposite effect. Isolated working rat hearts were reperfused after 10 min of global ischemia, measuring hemodynamic variables, tissue high energy phosphate compounds and purine release. In post-ischemic recovery, aortic flow and minute work decreased to 82 +/- 3% and 77 +/- 4% of control, adenine nucleotide pool was reduced by 4.6 mumol/g dry wt, phosphocreatine to creatine ratio increased significantly and purine release decreased to 42 +/- 6% (P < 0.01). The rate of purine salvage, as evaluated by the incorporation of exogenous 3H-adenosine and 14C-hypoxanthine into tissue nucleotides, was much lower than net purine release, and was unchanged after ischemia and reperfusion. The adenine nucleotide pool could be depleted to the same extent as in the stunned myocardium by prolonged (60 min) aerobic perfusion. In this group the hemodynamic variables were unchanged and purine release averaged 87 +/- 9% of control (P = NS). In other experiments prolonged perfusion was combined with preload reduction in order to decrease energy demand. This protocol reproduced the effects of ischemia-reperfusion: aortic flow and minute work averaged 79 +/- 4% and 73 +/- 9% of control, adenine nucleotide depletion was 4.4 mumol/g dry wt and purine release decreased to 38 +/- 5% (P < 0.01). Our findings support the view that stunning is not due to adenine nucleotide depletion or to impairment in energy production, which would cause purine release to increase, but rather to primary reduction in energy utilization.

Animals↗

PubMed2006

The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men?

PURPOSE: We examined pooled baseline data from 2 lipid treatment studies to evaluate the relationship among total serum testosterone levels, obesity and the metabolic syndrome in aging men. MATERIALS AND METHODS: Baseline total serum testosterone, lipid, glycemic and anthropometric data were obtained from 864 men (mean age 52 years) participating in 2 lipid treatment studies. Inclusion criteria for the 2 studies included low-density lipoprotein cholesterol 130 to 160 mg/dl and triglycerides 350 mg/dl or less. RESULTS: For all patients as well as the nonmetabolic syndrome and the metabolic syndrome cohorts, testosterone decreased with increasing body mass index (p < 0.0001 for Pearson correlation coefficient in all 3 cohorts). Mean baseline total serum testosterone levels in obese and severely obese aging men with the metabolic syndrome were around 150 and 300 ng/dl, respectively, less than that in aging, lean men with no metabolic syndrome. The relative contributions of each of the individual National Cholesterol Education Program Adult Treatment Panel III components of the metabolic syndrome to low serum testosterone in aging men was examined using multiple linear regression modeling. Based on these analyses the presence of diabetes or fasting serum glucose greater than 110 mg/dl, body mass index 30 kg/m or greater, and triglycerides 150 mg/dl or greater each appeared to have a clinically relevant association with low serum testosterone. CONCLUSIONS: This study demonstrated that aging men with obesity and the metabolic syndrome have a significant decrease in total serum testosterone levels compared to aging, metabolically healthy men. These data suggest that the well established association between erectile dysfunction and pre-diabetes/diabetes (particularly in obese pre-diabetic/diabetic patients) may involve a hormonal component.

Age Factors↗

PubMed1997

[Consequences of cholestasis from the hepatologist's viewpoint].

Chronic cholestasis is associated with a variety of symptoms and dysfunction of most organs. Among them, jaundice and pruritus are the first to be recognized, usually prompting the patients to see a physician. Besides the skin, however, cholestasis also affects, inter alia, the metabolism of plasma lipids and fat-soluble vitamins, as well as bone and liver. In the following article the pathogenesis and therapy of metabolic disturbances and organ dysfunctions occurring frequently in patients with chronic cholestasis are discussed.

Bone Diseases, Metabolic↗

PubMed1984

Disorders of the adrenal cortex: their effects on electrolyte metabolism.

The adrenal cortex is an important factor in the control of electrolyte and water balance and in blood pressure homeostasis. Not surprisingly, therefore, hyper- and hyposecretion of one or more of its products has extensive repercussions. Hypersecretion of aldosterone, as seen in primary hyperaldosteronism and related diseases, and of other mineralocorticoids such as corticosterone and/or 11-deoxycorticosterone, as seen in 17 alpha-hydroxylase deficiency or 11 beta-hydroxylase deficiency syndromes, respectively, are associated with hypertension, sodium retention, potassium wastage and a metabolic alkalosis. On the other hand, impaired secretion, as in Addison's disease or in congenital deficiencies of other steroid-synthesizing enzymes, leads to hypotension, sodium loss with hypovolaemia, and hyperkalaemia. In each case, these disturbances of electrolyte metabolism may cause neurological and muscle dysfunction. The relationship between glucocorticoid hypertension and electrolyte metabolism is less clear and the importance of the adrenal cortex in the aetiology of essential hypertension is still being assessed.

Addison Disease↗

PubMed1998

Dextromethorphan and dextrorphan in rats: common antitussives--different behavioural profiles.

Dextromethorphan (DM), a widely used and well-tolerated centrally acting antitussive, has been tested in several clinical trials for its antiepileptic and neuroprotective properties. However, the use of DM in these new clinical indications requires higher doses than antitussive doses, which may therefore induce phencyclidine (PCP)-like side-effects (memory and psychotomimetic disturbances) through its metabolic conversion to the active metabolite dextrorphan (DX), a more potent PCP-like non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor than DM. Thus, we compared the behavioural effects in rats of intraperitoneal administration of DM and DX on motor activity in an open field and on learning and memory in the Morris water maze. DM (20, 30, 40 mg/kg) produced a dose-dependent decrease in both locomotion and stereotyped behaviour with a slight ataxia for the highest dose. DX (20, 30, 40 mg/kg) induced a dose-dependent increase in locomotion and stereotypies (swaying, turning) with moderate ataxia. Assessments of learning and memory were performed with lower doses of DM (10, 20, 30 mg/kg) and DX (5, 10, 15 mg/kg) because of motivational deficits (40 mg/kg of DM, 20-40 mg/kg of DX) and motor disorders (30, 40 mg/kg of DX) in the cue learning procedure. DX (10, 15 mg/kg) impaired spatial learning with a long-lasting effect for the highest dose whereas 5 mg/kg of DX and DM (10-30 mg/kg) did not. Only 15 mg/kg of DX appeared to slightly impair working memory. DM (10-30 mg/kg) and DX (5-15 mg/kg) did not impair reference memory. Thus, the two antitussives DM and DX induced different behavioural effects suggesting sedative effects for DM and PCP-like effects for DX. However, PCP-like side-effects with DM remain possible through its metabolic conversion to DX, with very high doses and/or in extensive metabolizers and/or in aged subjects prone to cognitive dysfunction. Therefore, the identification of DM metabolism phenotype, an adapted prescription and a pharmacological modulation of the DM metabolism may avoid adverse effects.

Animals↗

PubMed1994

Osteoporosis from the point of view of the clinical endocrinologist.

The physiology of the bone tissue is reviewed from the point of view of a clinical endocrinologist. The effect of the main calcium-regulating hormones and various local factors on the osteoblasts and osteoclasts is discussed. The aim of this review is to summarize the physiological and pathophysiological role of calcitonin, parathormone, vitamin D3, thyroid hormones, glucocorticoids, growth hormone and sex hormones on bone metabolism. The significance of endocrinological dysfunctions in the pathogenesis of osteoporosis, the most wide-spread metabolic bone disease, is emphasized. A theory concerning the pathogenetic role of androgen hormone deficiency in postmenopausal osteoporosis is discussed in detail.

Bone Remodeling↗