Baroreflex deficit blunts exercise training‐induced cardiovascular and autonomic adaptations in hypertensive rats

1. Baroreceptors regulate moment‐to‐moment blood pressure (BP) variations, but their long‐term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex‐mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long‐term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50–70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re‐established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.     

Malaria and mosquito net utilisation among schoolchildren in villages with or without healthcare facilities at different altitudes in Iringa District, Tanzania

Background

The endemicity of malaria in Tanzania is heterogenous, mainly associated with physical factors such as topography, climate and socio-economic status. The contributions of these factors in many regions of Tanzania have not been studied in detail.

Objective

This study was carried out to determine the prevalence and transmission of malaria and mosquito nets coverage among schoolchildren in relation to altitude in villages with or without healthcare facilities in Iringa District,Tanzania.

Methods

A cross-sectional survey of schoolchildren was carried out in six villages in three altitude transects (965–2075 m). In each transect a village with and without a healthcare facility were selected. The villages included Idodi (965m), Makifu (985m), Tosamaganga (1561m) Mangalali (1520m) Lulanzi (1917) and Kilolo (2075m). For the purpose of this study, the villages were categorised as lowlands (Idodi and Makifu), intermediate (Tosamaganga and Mangalali) and highlands (Lulanzi and Kilolo. Healthcare facilities were available at Idodi,Tosamaganga and Kilolo. Each child was asked whether or not slept under a mosquito net during the previous night. Mosquitoes were collected using pyrethrum spray catch technique in ten houses in each study village.

Results

Blood smears from a total of 1643 schoolchildren (mean age = 5.9–12.3 years) were examined for malaria infection. Plasmodium falciparum accounted for 93.1% of the malaria parasites. The prevalence of P. falciparum among children in Idodi, Makifu, Mangalali,Tosamaganga, was 51.51%, 73.66%, 22.79%, and 14.83%, respectively. Malaria parasites were not found among children in the highland villages of Lulanzi and Kilolo). The prevalence of malaria parasitaemia, packed cell volume, geometric mean parasite density and spleen rates were higher in children living in villages without healthcare facilities (P<0.001). Of the children, 16.1% (264/1643) slept under a mosquito net during the previous night. About three quarters (253/344) of the schoolchildren who had malaria parasites were not using mosquito nets. Mosquito net coverage was higher in lowland villages, accounting for 61.7% (163/264) of the total net use in the district. The majority (75.5%) of the mosquito net users were from village with health facilities (P<0.001). A total of 228 mosquitoes were collected, with Anopheles gambiae s.l. accounting for the majority (53.5%). Overall, 8.7% of the An. gambiae s.l. were infected with malaria sporozoites. Higher sporozoite rates were observed in mosquitoes collected in the lowlands.

Conclusion

Communities living in areas without health facilities form the largest proportion of malaria-infected populations in Iringa district. Availability of healthcare service has an influence on mosquito net coverage. The results provide more evidence of the existence of a relationship between altitude variability or accessibility to healthcare services, and the burden of malaria in rural communities of Tanzania.     

Plasminogen receptors, urokinase receptors, and their modulation on human endothelial cells

Endothelial cells are centrally involved in regulation of fibrinolysis, and receptors for plasminogen and urokinase provide a mechanism by which cells can regulate their fibrinolytic function. Therefore, the existence and characteristics of receptors for these fibrinolytic components on cultured human umbilical vein endothelial cells were examined. We verified the presence of plasminogen receptors on these cells (Kd = 2.1 +/- 1.3 mumol/L, and 1.8 +/- 1.3 x 10(7) binding sites/cell). These binding parameters and other characteristics indicate that these receptors are closely related to the plasminogen receptors on many circulating and adherent cells. Specific binding sites that interact with two-chain urokinase of mol wt 55,000 with a dissociation constant of 2.1 +/- 1.7 nmol/L, with 2.9 +/- 2.9 x 10(5) sites/cell were also identified. Single-chain urokinase of mol wt 55,000, but not the two-chain degradation product of mol wt 33,000 bound to the cells, implicating the amino-terminal aspects of the ligand in receptor recognition. When endothelial cells were stimulated with thrombin, an agent that modulates their fibrinolytic potential, both receptor types were modestly affected; urokinase binding increased 17%, whereas plasminogen binding decreased 19%. The presence and modulation of plasminogen and urokinase receptors provide a potentially important additional mechanism by which endothelial cells may regulate fibrinolysis.     

The nexus of evidence,context, and patient preferences in primary care: postal survey of Canadian family physicians

Background  

Evidence-based medicine is gaining prominence in primary care. This study sought to examine the relationships among family physicians' attitudes toward EBM, contextual factors, and clinical decision-making and to investigate the factors that contribute to 'contrary to evidence' clinical decisions.     

Appearance of glucoprivic control of feeding behavior in the developing rat

2-Deoxyglucose was administered to determine whether glucoprivation would shorten either suckling or nibbling latencies of fed pups studied on Days 10, 14, 17, 21 and 24. A dosage of 200 mg/100 g BW given IP 2 hr prior to latency studies, shortened suckling latencies on Day 24, but shortened nibbling latencies from Day 21 onward. It is concluded that glucoprivic feeding control appears in the developing rat by Day 21 and affects nibbling behavior to a greater extent than suckling behavior.     

DNA databanks and consent: A suggested policy option involving an authorization model

Background

Genetic databases are becoming increasingly common as a means of determining the relationship between lifestyle, environmental exposures and genetic diseases. These databases rely on large numbers of research subjects contributing their genetic material to successfully explore the genetic basis of disease. However, as all possible research questions that can be posed of the data are unknown, an unresolved ethical issue is the status of informed consent for future research uses of genetic material.

Discussion

In this paper, we discuss the difficulties of an informed consent model for future ineffable uses of genetic data. We argue that variations on consent, such as presumed consent, blanket consent or constructed consent fail to meet the standards required by current informed consent doctrine and are distortions of the original concept. In this paper, we propose the concept of an authorization model whereby participants in genetic data banks are able to exercise a certain amount of control over future uses of genetic data. We argue this preserves the autonomy of individuals at the same time as allowing them to give permission and discretion to researchers for certain types of research.

Summary

The authorization model represents a step forward in the debate about informed consent in genetic databases. The move towards an authorization model would require changes in the regulatory and legislative environments. Additionally, empirical support of the utility and acceptability of authorization is required.