Thiazolidinediones--tools for the research of metabolic syndrome X

Recent studies have demonstrated that the expression of Fas by peripheral T cells from HIV-1+ patients is deregulated and increases the susceptibility of these cells to undergo apoptosis. Here, we show that secretion of Fas-ligand (L), the complementary agonist of Fas, is abnormally upregulated in CD4+ cells from HIV-1-infected individuals, particularly during the non-lymphopenic stages of the disease. An increase of soluble Fas-L occurred in T cell cultures from 26 patients with a number of CD4+ cells higher than 400/microliter, whereas it was almost undetectable in cultures from 21 severely lymphopenic patients (CD4+ < 200/microliter). The MTT test, cytofluorimetric analysis of cellular DNA, cytotoxicity, and proliferative assays using the Fas-transfected WC8 mouse lymphoma confirmed the cytocidal capability of T cell supernatants from non-lymphopenic patients. Double-fluorescence analysis revealed that the majority of CD4+ cells (approximately 90%) in these cultures secreted Fas-L in the presence of high intracellular gamma-interferon and low Bcl-2. In contrast, the CD8+/Fas-L+ population was comparably decreased (approximately 55%). Molecular cloning of Fas-L revealed a substantial expression of Fas-L mRNA in cells from non-lymphopenic patients compared with patients with advanced disease and healthy controls. Since CD4+ cells of Th1 phenotype are impaired during HIV-1 infection and show high cellular expression of Fas-L, it is conceivable that excess Fas-L during the early or non-lymphopenic phase of the disease increases the extent of apoptosis in these cells by the Fas/Fas-L pathway. The defective expression of the ligand in severely lymphopenic stages could be explained by exhaustion of this mechanism as the disease progresses.     

Perspectives and molecular diagnosis of the fragile X syndrome

The fragile X syndrome is the most common mendelianly inherited form of mental retardation. The underlying mutation is usually a triplet repeat (CGG) that is variable in length and undergoes a tremendous length amplification in affected individuals. The mutation leads to absence expression of a gene, which apparently functions as an RNA binding protein. Molecular diagnostic testing for the mutation is conducted using direct genomic Southern blot analysis and polymerase chain reaction. Because the mutation is so common and a single type of mutation accounts for most individuals with the disease, widespread genetic screening can be considered.     

Enhanced activity of sodium-lithium countertransport in patients with cardiac syndrome X: a potential link between cardiac and metabolic syndrome X

OBJECTIVES: This study was aimed at assessing both stimulated insulinemia and the sodium-lithium countertransport in a selected group of patients with cardiac syndrome X. BACKGROUND: Hyperinsulinemia, which is frequently present in patients with cardiac syndrome X, is often associated with an enhanced activity of the sodium-lithium countertransport, an in vitro marker of sodium-hydrogen exchange. METHODS: Fifteen patients with syndrome X and 14 matched controls were studied. After pharmacological washout, sodium-lithium countertransport was assessed from lithium-loaded red blood cells. Postload insulin levels were evaluated by a double-antibody radioimmunoassay. RESULTS: Maximal velocity of sodium-lithium countertransport was higher in patients with syndrome X compared to controls (635+/-200 vs. 324+/-49 micromol/liter/h, p = 0.001). Fourteen of the 15 patients with syndrome X (93%) presented sodium-lithium countertransport values higher than the mean +2 SD of the control group. At 120 min, 12 patients with syndrome X (80%) had plasma levels of insulin >420 pmol/liter, which corresponds to the mean value +2 SD of controls (p = 0.006). CONCLUSIONS: Both enhanced activity of the sodium-lithium countertransport and stimulated hyperinsulinemia are present in the vast majority of patients with cardiac syndrome X. As enhanced activity of the sodium-lithium countertransport has the potential to cause both glucose intolerance and smooth muscle hyperreactivity, it might represent a common cause of the metabolic and vascular alterations frequently found in syndrome X.     

Dipyridamole technetium-99m Sestamibi imaging in the diagnosis of syndrome X

In a middle-aged woman with anginal chest pain and a normal-appearing angiogram, dypiridamole technetium-99m Sestamibi scintigraphy, a noninvasive method, provided the diagnosis of syndrome X and was used in follow-up to monitor the course of disease.     

The fragile X syndrome

The aim of this study was to investigate the role of nitric oxide in metabolic disturbances induced in brain tissue of fetal guinea pigs by oxygen-glucose deprivation. Experiments were performed on hippocampal slices so as to exclude the effects of nitric oxide on the cardiovascular system. Metabolic disturbances were assessed by measuring changes in energy metabolism and protein synthesis after different periods of oxygen-glucose deprivation (OGD). Ten min after OGD of 40 min duration, the concentration of cGMP in tissue slices rose from 1.35 +/- 0.38 to 18.6 +/- 1.04 pmol/mg protein (P < 0.05). This rise was almost completely inhibited by the addition of 100 microM N-nitro-L-arginine (NNLA), indicating that NO-synthase was strongly activated after OGD in fetal brain tissue. However, addition of NNLA improved neither protein synthesis nor energy metabolism measured 12 h after OGD. Thus, nitric oxide does not appear to contribute directly to processes leading to metabolic disturbances induced by transient ischemia in immature brain tissue.     

Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM

Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1C over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P < 0.0005), UFC and OGTT glucose area under the curve (AUC) (P < 0.01), and UFC and HbA1C (P < 0.005). UFC levels were negatively correlated (P < 0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia. Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension. However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect "toxic" effect on the beta-cell.     

The metabolic anatomy of Tourette's syndrome

The functional brain networks underlying the clinical manifestations of Gilles de la Tourette's syndrome (TS) are currently unknown. To identify these networks, we studied TS patients and normal subjects with 18F-fluorodeoxyglucose (FDG) and PET employing a statistical model of regional metabolic covariation. We studied 10 TS patients (mean age, 41.5 +/- 12.7 years) who were either drug naive or medication free for at least 2 years. Ten normal volunteers (mean age, 42.5 +/- 11.5) served as controls. We used quantitative FDG/PET to calculate global, regional, and normalized rates of glucose metabolism (GMR, rCMRGlc, and rCMRGlc/GMR) in all subjects. The Scaled Subprofile Model (SSM) was used to identify specific patterns of regional metabolic covariation associated with TS. We found that global and regional metabolic rates were normal in TS. SSM analysis identified two TS-related brain networks. One pattern (15.8% variance accounted for, VAF) was characterized by covariate bilateral metabolic increases in lateral premotor and supplementary motor association cortices and in the midbrain. Individual patient expression of this pattern (subject score) was abnormally increased in the TS group (p < 0.01). A second pattern (10.5% VAF) was characterized by covariate decreases in caudate and thalamic metabolism associated with smaller reductions in lentiform and hippocampal metabolic activity. Subject scores for this pattern correlated with Tourette Syndrome Global Scale (TSGS) global ratings (r = 0.85, p < 0.005). We conclude that the metabolic landscape of TS is characterized by a nonspecific pattern of increased motor cortical activity identified in other hyperkinetic disorders. TS is also associated with a specific brain network characterized by a reduction in the activity of limbic basal ganglia-thalamocortical projection systems.     

Individual housing influences certain biochemical parameters in the rat

OBJECTIVE: A modified Abbe flap of the lambda figure type, designed by the author and used before or after secondary cleft lip repair in 146 consecutive cases since 1990 is described. DESIGN: This series consisted of 71 cases with unilateral deformity and 75 cases with bilateral deformity at adolescent or adult ages. The technical details of this method and representative cases with the results are shown. The philtrum is created by incising the two branches of the lambda flap obliquely at 45 degrees to the skin surface in the lower lip, then matching them in the central recipient bed of the deficient upper lip. RESULTS AND CONCLUSIONS: The resultant upper lip is not only full and slack, but also attractive with an acute cubic contour of the philtrum. Furthermore, the residual scar at the donor site is concealed in the mentolabial fold.     

An investigation of the validity of certain tempering parameters

The underlying assumptions involved in the use of a variety of tempering parameters have been examined and compared critically with experimental results for a plain carbon steel. It is found that the assumptions and experimental results are in conflict for any simple parameter but, because of the insensitivity of their mathematical forms to changes in tempering time, certain parameters are capable of adequate representation of the hardness changes which occur during tempering. The widely used Hollomon-Jaffe parameter is found to be the most successful in covering a wide range of hardness changes.     

The role of radiologic methods in assessing body composition and related metabolic parameters

The measurement of body composition and related metabolic parameters has become an important issue in clinical nutrition. Numerous techniques to assess visceral fat, which is strongly associated with metabolic disorders, have been developed. Other techniques focus mainly on the measurement of specific body components related to metabolic disturbances. This paper reviews methods that directly assess body composition and associated metabolic parameters. The principles of these methods and their accuracy, reproducibility and safety, as well as the clinical implications of their use, are discussed. Recent studies have documented the safety and efficacy of radiologic methods of assessing visceral fat, muscle mass, and morphology to obtain body composition data related to metabolic disturbances. Because these techniques have been documented to be safe and effective, clinicians should consider using them in the evaluation and follow-up of patients with various conditions.     

The value of laparoscopy in the diagnosis and treatment of non-palpable testicular cryptorchism

Laparoscopy is useful in both the diagnosis and the management of impalpable testes. Intra-abdominal testicles can be removed laparoscopically if atrophic or can be partly devascularized by spermatic vessel clipping if apparently normal. Assessment of testicular revascularization would be desirable prior to subsequent orchidopexy. A second-stage vasal-based orchidopexy can then be performed once adequate testicular reperfusion via the deferential pedicle is believed to have occurred. We have used both diagnostic and therapeutic laparoscopy in the management of 103 non-palpable testes over a period of 6 years. Open procedures following laparoscopy included 57 orchidopexies, 11 orchiectomies and one microvascular testicular autotransplant. Thirteen laparoscopic interventions were performed: 5 orchiectomies for atrophic testes and 8 testicular vessel clippings followed by 6 second stage open inguinal orchidopexies. Color Doppler duplex ultrasonography was not found to be reliable for assessment of testicular revascularization following spermatic vessel clipping. There were 3 complications which were all related to puncture with the Veress needle.     

Esophageal dysfunction in syndrome X

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing or myocardial scintigraphy, but with angiographically "normal" coronary arteries. The etiology of this enticing syndrome is still not known. Besides myocardial ischemia, esophageal dysfunction and visceral hypersensitivity may play a role in the development of pain. The purpose of this study was to study esophageal function and visceral sensitivity in patients with syndrome X. Twenty consecutive patients with the diagnosis of syndrome X were investigated with esophageal manometry and a 24-hour pH recording. Visceral esophageal sensitivity was explored by balloon distention of the distal esophagus, as well as by instillation of acid. Twelve patients (67% of the 18 evaluated) had some abnormality on 24-hour pH monitoring; 2 had abnormal global acid exposure time (pH <4) and 7 had symptoms coincidental with episodes of pH <4. Seven patients (35%) had esophageal dysmotility including 5 with the "nutcracker" esophagus. Esophageal hypersensitivity to acid (n = 9) or distention (n = 13) was seen in 14 of the 20 patients. Eleven patients received acid suppressive therapy that resulted in amelioration of chest pain in 8 (73%). Thus, results suggest that esophageal hypersensitivity rather than gross functional abnormality is an important factor for the development of chest pain in patients with syndrome X, and that acid in the context of a hypersensitive esophagus is the main culprit. Acid suppression may ameliorate pain in a substantial proportion of patients.     

The association between selected metabolic parameters and left abomasal displacement in dairy cows

The objective of this study was to examine the association between selected metabolic parameters and subsequent left displaced abomasum (LDA) diagnosis in dairy cows. Forty-four LDA cows sampled in the third week ante partum (a.p.) which was at a median of 34 days prior to LDA diagnosis, 36 LDA cows sampled in the first week post partum (p.p.) which was at a median of 14 days prior and 28 LDA cows sampled in the second week p.p., which was at a median of 9 days prior to LDA diagnosis were used. Each case was matched to 3 controls by herd and calving date. Data were available from a large field study. Aspartate-aminotransferase (AST) activity, the concentrations of beta-hydroxybutyrate (BHB), glucose, calcium and urea in blood, and the body condition score (BCS) were studied. Logistic regression was used to analyse the association between these parameters and subsequent LDA, adjusting for the effects of parity and pretreatment. A separate model was used for each sampling week and each parameter. In the third week a.p. none of the parameters were significantly associated with LDA. AST and BHB sampled in the first week p.p. and in the second week p.p. were significantly associated with LDA diagnosis. The higher the AST and BHB, the higher the odds of being diagnosed subsequently with LDA. The lower glucose and Ca in the second week p.p. the higher the odds of subsequent LDA diagnosis. Urea and BCS were not significantly associated with LDA in any of the weeks examined. We conclude that AST and BHB in the first and second week p.p. might be used as tests for subsequent LDA. Glucose, calcium, urea and body condition were either not significantly associated with LDA or significantly associated only in the second week p.p.; this may limit their use as tests for LDA.