Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

Endothelial reactivity to the immediate hypersensitivity reaction of guinea pig pulmonary artery

Ovalbumin at low doses (0.1 microg/ml) caused pronounced relaxations in the precontracted pulmonary arteries of sensitized guinea pigs but, at high doses, (1-100 microg/ml) the relaxations were blunted by the contractions. The relaxations in response to ovalbumin challenge were related to histamine, which is released during the immediate hypersensitivity reaction, because they were almost blocked by mepyramine (10(-5) M) plus cimetidine (10(-4) M) pretreatment and never observed in unsensitized animal arteries. Additionally, the inhibition of relaxations by endothelium removal or N(G)-nitro-L-arginine (L-NOARG, 10(-4) M) treatment implies that the phenomenon requires endothelial nitric oxide synthesis. However, the contractions appear to depend on leukotriene production since they were markedly blocked in the presence of 2(S)-hydroxy-3(R)-[(2-carboxyethyl)thio]-3-[2-(8-phenyloctyl)pheny l]- propanoic acid (SKF 104353, 10(-5) M), a leukotriene receptor antagonist. These results indicate that ovalbumin-induced nitric oxide and histamine H(2) receptor dependent relaxations in pulmonary artery may have an important role in the recovery of the increased pulmonary vascular resistance during the hypersensitivity reaction.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.     

Conduction abnormalities in nonischemic dilated cardiomyopathy: basic mechanisms and arrhythmic consequences

Heart failure is associated with an increased risk of sudden death caused by ventricular tachyarrhythmias. The role of altered repolarization in the formation of arrhythmogenic substrates and triggers has been studied at multiple levels of integration, including molecular, cellular, tissue, and organ levels. Numerous studies have focused on conduction abnormalities in the context of ischemic heart disease and left ventricular dysfunction after myocardial infarction. However, ischemia alone, independent of left ventricular dysfunction, alters conduction by depressing membrane excitability and increasing tissue resistivity. In this review, we focus on the role of conduction abnormalities in the genesis of arrhythmias in nonischemic dilated cardiomyopathy and discuss their underlying cellular and molecular mechanisms, including changes in myocyte excitability, the extracellular matrix, and cell-to-cell coupling. We compare the nature of conduction slowing in ischemic and nonischemic heart failure and highlight the mechanistic differences between the two disease etiologies.     

Factor V 1691 G-A mutation in children with intracardiac thrombosis: a prospective study

The objective of this study was to determine the association between intracardiac thrombosis and hereditary causes of thrombophilia, including factor V 1691 G-A (factor V Leiden, FVL) and prothrombin 20210 G-A mutations. Over a period of 3 y, genetic risk factors were evaluated in 13 consecutive children (mean age 6.27 ±5.44 y) with intracardiac thrombosis, diagnosed by cross-sectional echocardiography. Thrombi were localized in the left heart in four patients and the right heart in nine patients. All children had predisposing factors for thrombus formation: ventriculoatrial shunt for hydrocephalus ( n = 3), indwelling catheter for chemotherapy ( n = 5), cardiomyopathy ( n = 2), sepsis ( n = 1), homocystinuria ( n = 1) and tetralogy of Fallot ( n = 1). Six of the 13 children with intracardiac thrombosis were heterozygotes for FVL mutation. Three of these six children with FVL mutation had ventriculoatrial shunt for hydrocephalus, two children had cardiomyopathy and one had sepsis. None of the patients carried the prothrombin 20210 G-A mutation.

Conclusion : It is recommended that FVL mutations should be investigated in all cases of intracardiac thrombosis irrespective of whether or not a predisposing factor is identified. When a predisposing factor is found antithrombotic prophylaxis may be considered in patients carrying the FVL mutation.     

The Effects on Health Behavior and Health Outcomes of Internet-Based Asynchronous Communication Between Health Providers and Patients With a Chronic Condition: A Systematic Review

Background

In support of professional practice, asynchronous communication between the patient and the provider is implemented separately or in combination with Internet-based self-management interventions. This interaction occurs primarily through electronic messaging or discussion boards. There is little evidence as to whether it is a useful tool for chronically ill patients to support their self-management and increase the effectiveness of interventions.

Objective

The aim of our study was to review the use and usability of patient-provider asynchronous communication for chronically ill patients and the effects of such communication on health behavior, health outcomes, and patient satisfaction.

Methods

A literature search was performed using PubMed and Embase. The quality of the articles was appraised according to the National Institute for Health and Clinical Excellence (NICE) criteria. The use and usability of the asynchronous communication was analyzed by examining the frequency of use and the number of users of the interventions with asynchronous communication, as well as of separate electronic messaging. The effectiveness of asynchronous communication was analyzed by examining effects on health behavior, health outcomes, and patient satisfaction.

Results

Patients’ knowledge concerning their chronic condition increased and they seemed to appreciate being able to communicate asynchronously with their providers. They not only had specific questions but also wanted to communicate about feeling ill. A decrease in visits to the physician was shown in two studies (P=.07, P=.07). Increases in self-management/self-efficacy for patients with back pain, dyspnea, and heart failure were found. Positive health outcomes were shown in 12 studies, where the clinical outcomes for diabetic patients (HbA1c level) and for asthmatic patients (forced expiratory volume [FEV]) improved. Physical symptoms improved in five studies. Five studies generated a variety of positive psychosocial outcomes.

Conclusions

The effect of asynchronous communication is not shown unequivocally in these studies. Patients seem to be interested in using email. Patients are willing to participate and are taking the initiative to discuss health issues with their providers. Additional testing of the effects of asynchronous communication on self-management in chronically ill patients is needed.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective　To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods　Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results　All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion　Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.