Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

Alterations in sympathetic nervous system activity do not regulate adipsin gene expression in mice.

Adipsin gene expression is severely diminished in certain forms of genetic and acquired rodent obesity. Common to many of these models of obesity is decreased sympathetic nervous system (SNS) activity. In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity. Based on these observations, we hypothesized that adipsin gene expression might be regulated through changes in SNS activity with deficient adipsin gene expression in obesity being the result of impaired SNS activity. In the present study we used three models to assess the role of the SNS in regulating adipsin gene expression. First we exposed mice to the cold (4 degrees C), a potent activator of SNS activity. Second, we chemically sympathectomized mice with 60H-dopamine. Third, we treated mice with BRL 26830A, an atypical beta adrenoreceptor agonist. In contrast to our initial hypothesis, these studies demonstrate that alterations of SNS activity do not affect adipsin gene expression in normal mice. Neither increased SNS activity secondary to cold exposure nor decreased SNS activity resulting from sympathectomy alter serum adipsin concentration or adipsin mRNA levels in white (WAT) and brown adipose tissue (BAT). Surprisingly, treatment of lean mice with BRL 26830A decreases both adipsin serum concentrations and adipsin mRNA levels, suggesting a potential role for atypical beta adrenoreceptors in pathways that suppress adipsin expression in vivo. The significance of this observation with respect to adipocyte physiology is unclear at present. Future studies will be aimed at defining the molecular mechanisms by which BRL 26830A suppresses adipsin gene expression and the physiological significance of this effect.     

Characterization of binding and phosphorylation defects of erythrocyte insulin receptors in the type A syndrome of insulin resistance

The type A syndrome of insulin resistance and acanthosis nigricans is characterized by severe insulin resistance due to a cellular defect in insulin action. To better understand the molecular nature of this defect, we have investigated insulin binding to circulating monocytes, erythrocytes, and the Triton X-100-solubilized erythrocyte receptor, and insulin-stimulated receptor autophosphorylation using cells and receptor from three type A patients. Insulin binding in both circulating cells and the soluble extract of erythrocytes indicated a heterogeneity of defects. Patients A1 and A2 both presented a major decrease in tracer insulin binding to intact cells and soluble insulin receptor. Determination of stoichiometric binding parameters using a cooperative model indicated that in patient A1 this was due to a reduction in the number of receptors, whereas in patient A2 the affinity constant for binding was decreased. Patient A3 presented near-normal insulin binding to erythrocytes and normal binding in intact monocytes, solubilized erythrocyte receptors, and cultured fibroblasts. Affinity labeling of erythrocyte receptor from this patient revealed a normal alpha-subunit and also a normal relative distribution of the higher-molecular-weight, nonreduced oligomeric forms of the receptor. Receptor autophosphorylation was measured using the solubilized insulin receptor from erythrocytes. The maximal stimulated phosphorylation was reduced by 79%, 76%, and 52% in patients A1, A2, and A3, respectively, relative to the simultaneous control. In all three patients, the autophosphorylation was stimulated only 1.0-3.5 times the basal level compared with controls, in which the stimulation was 5.7-fold +/- 1.2 (mean +/- 1 SD, P less than 0.005). In addition, in patients A1 and A2 a decrease in basal phosphorylation was observed and in patient A2 there was a rightward shift of the dose-response curve for insulin stimulation. These data and the correlation of coupling of receptor phosphorylation with the fractional occupancy of the receptor measured in the same extract suggest that these patients exhibit three types of defects. In patient A1, there is a loss in receptor number manifested by a parallel decrease in insulin binding and receptor phosphorylation. In patient A2, there is an additional decrease in the affinity constant leading to a decrease in both binding and receptor phosphorylation with an almost linear coupling between receptor occupancy and receptor phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Is Functional Dyspepsia of Particular Concern in Women? A Review of Gender Differences in Epidemiology, Pathophysiologic Mechanisms, Clinical Presentation, and Management

Dyspepsia is a remarkably common symptom in the general population. Although multiple definitions have been used to describe the symptom, the most common explanation is that of chronic or recurrent pain or discomfort (a subjective negative feeling that may be associated with early satiety, fullness, bloating, or nausea) centered in the upper abdomen. When a thorough evaluation of a dyspeptic patient fails to identify a cause for her symptoms, the label of nonulcer or functional dyspepsia is applied. Functional dyspepsia is a heterogeneous disorder characterized by relapsing and remitting symptoms. Treatment strategies should focus on alleviating the most bothersome symptom and can be based on the proposed underlying pathophysiology. The effect of gender on mechanisms of disease, symptom presentation, and treatment response is an area of increasing interest and study. As with other functional gastrointestinal disorders, there appear to be some gender-specific features of functional dyspepsia. Specifically, gender-related differences have been observed in some studies of both the prevalence of individual dyspepsia symptoms, and in gastric emptying and proximal gastric motor function. There also appear to be gender differences in the psychosocial realm, with dyspeptic women experiencing a lesser sense of well-being than dyspeptic men, as well as an association of an abuse history with functional dyspepsia. This review will highlight specific gender differences related to the symptom presentation, pathophysiology, and approach to treatment of functional dyspepsia, while noting where differences have not been found and where further investigation is warranted.     

Reduced activity of the red-cell sodium-potassium pump in human obesity

Looking for evidence of reduced energy use in the cells of obese persons, we measured the numbers of sodium-potassium-pump units in erythrocytes from a group of 21 obese human subjects and found them to be reduced by 22 per cent as compared with those of nonobese controls (P <0.001). The cation-transport activity of the pump, as measured by 86rubidium uptake by the cells, we also reduced in parallel with decrease in pump units. An increased concentration of sodium in the red cells of obese subjectes was also found (9.6 +/- 0.7 vs. 7.1 +/- 0.6 mmol per liter of cells; P<0.01). This finding demonstrates independently the physiologic importance of reduced numbers of sodium-pump units and reduced pump activity as measured by ouabain binding and rubidium transport, respectively. The magnitude of the reduction in the number of pump units was found to be negatively correlated with the percentage of ideal body weight (r = 0.56, P<0.001); this observation suggests a possible role of abnormalities of the sodium pump in the pathophysiology of obesity.     

Augmentation of antigen-specific lymphoproliferative responses in vitro by biological response modifiers.

The detection of antigen-specific T cell responsiveness, particularly of resting memory lymphocytes, in cultures of peripheral blood mononuclear cells (PBMC) may be hampered by a less than optimal antigen presentation in vitro. Augmented sensitivity of the test system may be achieved by the addition of reagents with a beneficial effect on lymphocyte and antigen-presenting cell (APC) functions. In this study the effect of several biological response modifiers on antigen-specific T cell proliferation was determined, using nickel sulphate and tetanus toxoid as test antigens. IL-1 alpha (100 U/ml), interferon-gamma (IFN-gamma) (10 U/ml), and indomethacin (2 microM) were found to significantly enhance nickel-induced proliferation in PBMC cultures from nickel-hypersensitive donors (n = 6). Tetanus-induced proliferation (n = 5) was similarly enhanced, both by the above supplements and by the addition of polyethylene glycol (PEG) or a neuraminidase treatment of the PBMC before culture. The addition to PBMC cultures of a combination of IL-1 alpha (30 U/ml), IFN-gamma (10 U/ml), and indomethacin (2 microM) is recommended to specifically enhance antigen-induced lymphoproliferative signals.     

Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.     

Escherichia coli tetracycline efflux determinants in relation to tetracycline residues in chicken

ObjectiveTo screen for Escherichia coli (E. coli) resistant to tetracycline, followed by identification of tet efflux genes by polymerase chain reaction (PCR). In addition, detection of tetracycline residues in chicken livers and kidneys were conducted using high performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS).MethodsStrains of E. coli were isolated from samples of chicken colon and screened for tetracycline resistance. Tetracycline genes conferring resistance (Tc^r) were detected by polymerase chain reaction (PCR). Most of the isolates were resistant to tetracycline (97.9%).ResultsPCR analysis indicated that Tc^r E. coli R-plasmids contained tet(A), tet(B) and a combination of both efflux genes. None of the isolates contained other efflux tet genes tet (C, D, E and Y). High performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS), a sensitive technique, was used to detect residues of chlortetracycline (CTC), oxytetracycline (OTC), doxycycline (DC) in chicken livers and kidneys. The samples containing tetracycline residues were at 0.13-0.65 pg/μL levels.ConclusionsTetracycline and other antibiotics are commonly used in the poultry and meat production industry for prevention of microbial infections. Multiple antibiotic resistant bacteria in Oman have increased to alarming levels, threatening public health, domestic and may have adverse effect on environment.