Cardiac renin-angiotensin system (gene expression) and plasma angiotensin II in chickens with T3-induced pulmonary hypertension.

The relative expression of renin, angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) was performed using quantitative real-time PCR on tissue from the heart ventricles to investigate the effect of 3,5,3'-l-triiodothyronine (T3)-induced pulmonary hypertension syndrome (PHS) in broiler chickens at 12 and 42 d of age. Plasma angiotensin II was also measured using enzyme immunoassay at 12, 21, 28, 32 and 42 d. Renin transcript in the right ventricle of the treated group was significantly increased at 12 d and decreased at 42 d of age compared to controls. ACE transcript in the left ventricle of the treated group was significantly increased at 42 d of age compared to controls. In the right ventricle, the expression of this gene was significantly increased at 12 d while decreased at 42 d of age in the treated group compared to control. AT1R transcript in the right ventricle of the treated group was significantly increased at 12 and 42 d of age compared to control. In the left ventricle of the treated group, the transcript of this gene was only higher at 12 d of age than control. Plasma angiotensin II was significantly increased in pulmonary hypertensive chickens at 28 d of age compared to control. It is concluded that gene expression of renin, ACE and AT1R was relatively upregulated in the heart of chickens developing pulmonary hypertension. The right ventricle of hearts from pulmonary hypertensive chickens showed considerable reductions of renin/ACE and elevation of AT1R which may provide evidence of diminished responsiveness of the renin-angiotensin system.

Estimating quality-adjusted life years from patient-reported visual functioning.

PURPOSE: Glaucoma is an important disease, the impacts of which on vision have been shown to have implications for patients' health-related quality of life (HRQoL). The primary aim of this study is to estimate a mapping algorithm to predict EQ-5D and SF-6D utility values based on the vision-specific measure, the 25-item Visual Functioning Questionnaire (VFQ-25), as well as the clinical measures of visual function, that is, integrated visual field, visual acuity, and contrast sensitivity. METHODS: Ordinary least squares (OLS), Tobit, and censored least absolute deviations were compared using data taken from the Moorfields Eye Hospital in London, to assess mapping functions to predict the EQ-5D and SF-6D from the VFQ-25, and tests of visual function. These models were compared using root mean square error (RMSE), R(2), and mean absolute error (MAE). RESULTS: OLS was the best-performing model of the three compared, as this produced the lowest RMSE and MAE, and the highest R(2). CONCLUSIONS: The models provided initial algorithms to convert the VFQ-25 to the EQ-5D and SF-6D. Further analysis would be needed to validate the models or algorithms.

The dynamics of interactions between Plasmodium and the mosquito: a study of the infectivity of Plasmodium berghei and Plasmodium gallinaceum, and their transmission by Anopheles stephensi, Anopheles gambiae and Aedes aegypti.

Knowledge of parasite-mosquito interactions is essential to develop strategies that will reduce malaria transmission through the mosquito vector. In this study we investigated the development of two model malaria parasites, Plasmodium berghei and Plasmodium gallinaceum, in three mosquito species Anopheles stephensi, Anopheles gambiae and Aedes aegypti. New methods to study gamete production in vivo in combination with GFP-expressing ookinetes were employed to measure the large losses incurred by the parasites during infection of mosquitoes. All three mosquito species transmitted P. gallinaceum; P. berghei was only transmitted by Anopheles spp. Plasmodium gallinaceum initiates gamete production with high efficiency equally in the three mosquito species. By contrast P. berghei is less efficiently activated to produce gametes, and in Ae. aegypti microgamete formation is almost totally suppressed. In all parasite/vector combinations ookinete development is inefficient, 500-100,000-fold losses were encountered. Losses during ookinete-to-oocyst transformation range from fivefold in compatible vector parasite combinations (P. berghei/An. stephensi), through >100-fold in poor vector/parasite combinations (P. gallinaceum/An. stephensi), to complete blockade (>1,500 fold) in others (P. berghei/Ae. aegypti). Plasmodium berghei ookinetes survive poorly in the bloodmeal of Ae. aegypti and are unable to invade the midgut epithelium. Cultured mature ookinetes of P. berghei injected directly into the mosquito haemocoele produced salivary gland sporozoites in An. stephensi, but not in Ae. aegypti, suggesting that further species-specific incompatibilities occur downstream of the midgut epithelium in Ae. aegypti. These results show that in these parasite-mosquito combinations the susceptibility to malarial infection is regulated at multiple steps during the development of the parasites. Understanding these at the molecular level may contribute to the development of rational strategies to reduce the vector competence of malarial vectors.