Culture at low glucose up-regulates mitochondrial function in pancreatic β cells with accompanying effects on viability

We tested whether exposure of β cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike. An increased release of lactate dehydrogenase that followed exposure to hypoxia was attenuated in rat islets which had been pre-cultured at half standard glucose. In INS-1 cells exposure to half standard glucose attenuated hypoxia-induced effects on several viability parameters (MTT, cell number and incremental apoptotic DNA). Thus culture at reduced glucose of pancreatic islets and clonal β cells leads to mitochondrial adaptions which possibly lessen the negative impact of hypoxia on β cell viability. These findings appear relevant in the search for optimization of pre-transplant conditions in a clinical setting.     

Assessing parasitic infestation of vegetables in selected markets in Metro Manila,Philippines

ObjectiveTo assess the parasitic infestation of vegetables in selected markets in Metro Manila, Philippines.MethodsA total of 80 vegetables were purchased from public and private markets in Munoz, Quezon City, and Alabang, Muntinlupa City. Vegetables were washed, and the washings were collected and examined for parasitic organisms.ResultsIn all vegetables examined, 36 of 80 (45.0%) were infested with parasitic organisms. Vegetables obtained from Muntinlupa City showed that 17 of 40 (42.5%) have parasitic infestation as compared with those obtained from Quezon City with 19 of 40 (47.5%). Significant differences on the parasitic organisms existed between the public and private markets and between the two locations (P<0.05).ConclusionsFindings indicate that vegetables can be potential source of parasitic infection. There is a need to be vigilant in ensuring that foodstuffs sold in our market systems are safe and fit for consumption.     

Cardiac-Arrest-Zentren

Notfall + Rettungsmedizin -     

Death following ingestion of MDMA (ecstasy) and moclobemide

Four deaths following the ingestion of moclobemide and MDMA ('ecstasy') are described. The probable cause of death in each case was serotonin syndrome as a result of an interaction between the two drugs. As none of the victims had been prescribed moclobemide it seems that each had taken the drug to enhance the effects of MDMA, with fatal consequences. Warnings are needed against misinformed attempts to potentiate the pharmacological effects of illicit drugs.     

Hemostatic factors as predictors of coronary events and total mortality: The FINRISK '92 Hemostasis Study

The role of hemostatic factors as predictors of coronary heart disease (CHD) and total mortality is poorly understood. Therefore, we carried out a prospective cohort study in Finland. In 1992, a random population sample of 2378 men and women aged 45 to 64 years was investigated and then followed up until December 31, 1998. During the follow-up, 133 CHD events were observed; 73 were among participants free of CHD at baseline. The total number of deaths was 124. After adjustment for traditional risk factors and prevalent CHD at baseline and correction for regression dilution bias, a 1-SD increase in plasminogen was associated with a 1.41-fold (95% CI 1.09 to 1.81) increase in CHD risk. The predictive power of plasminogen depended significantly on the level of total cholesterol being stronger for persons with high cholesterol. A 1-SD increase in fibrinogen was associated with a 1.23-fold (95% CI 1.05 to 1.44) increase in all-cause mortality, but its association with CHD events did not reach statistical significance. Factor VII antigen or coagulant activity or lipoprotein(a) were not independent predictors of CHD risk. These findings support the role of plasminogen as a risk factor for CHD events.     

Does the calcium antagonist verapamil modify calcium metabolism?

In 11 healthy volunteers the effects of oral verapamil administration (4 X 80 mg/d) on plasma or serum concentrations of ionized, pH-corrected ionized and total calcium, on intact and midregional parathyroid hormone and on 24 h urinary excretion of calcium were investigated at rest. In addition the concentrations of ionized, pH-corrected ionized and total serum calcium were analyzed under bicycle exercise. Verapamil resulted in an increase of total serum calcium (p less than 0.02) and a fall in midregional parathyroid hormone concentrations (p less than 0.02) at rest. There was also found a statistically significant elevation of both ionized (p less than 0.05) and pH-corrected ionized (p less than 0.05) plasma calcium, and a slight increase in the total calcium under exercise (p less than 0.1). Before verapamil a significant negative correlation between total calcium and midregional parathyroid hormone was evident (r = -0.618; p less than 0.05), which however could not be clearly discerned after verapamil.     

Cardiac arrest and left ventricular fibrosis in a Finnish family with the lamin A/C mutation

Introduction: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms.
Methods and Results: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum.
Conclusion: These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.     

Interactions between peroxisome proliferator-activated receptor-gamma 2 gene polymorphisms and size at birth on blood pressure and the use of antihypertensive medication

OBJECTIVE: The combination of small birth size and the Pro12Pro variant of the peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma 2) gene has been shown to be associated with insulin resistance, which is linked to hypertension. We examined whether the association between small body size at birth and adult blood pressure is modulated by PPAR-gamma 2 gene polymorphism, and whether the use of any class of antihypertensive medication is related to birth size. DESIGN AND METHODS: A total of 500 subjects from an original epidemiological cohort of 7086 men and women aged 65-75 years attended a clinical study. Two hundred and eight of them (73 men and 135 women) were taking antihypertensive medication and are included in this study. The Pro12Ala polymorphism of the PPAR-gamma 2 gene was determined using the polymerase chain reaction single-strand conformation polymorphism method. RESULTS AND CONCLUSIONS: Hypertensive subjects with low birth weight or short length at birth and the Pro12Pro variant had raised systolic blood pressure. We suggest that insulin resistance enhances the regulatory responses of the renin-angiotensin system, leading to raised blood pressure levels. Those hypertensive subjects who had small birth size and the Pro12Pro variant tended to use angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB). This could be because insulin resistance interacts with the renin-angiotensin system in ways that make ACEI/ARB an effective therapy. Alternative explanations include more severe and treatment resistant hypertension, leading to application of ACEI/ARB, or co-morbid conditions, such as myocardial infarction and type 2 diabetes, known to be linked to low birth weight.