Relevance of apolipoprotein E polymorphism for coronary artery disease in the Saudi population

BACKGROUND: The apolipoprotein E alleles epsilon2 and epsilon4 have been reported as independent risk factors for coronary artery disease (CAD) and as predictors for the development of atherosclerosis. METHODS AND RESULTS: We determined by polymerase chain reaction the distribution of apolipoprotein E polymorphism in 320 Saudi blood donors (BD), 96 CAD patients, and 40 control subjects who had undergone angiography. Compared to controls, only epsilon4 was elevated in CAD patients. More than 61% (P <.0001) of the patients had angina, and 52.1% (P <.05) were diabetic; both of these factors were strongly associated with the presence of allele epsilon2. The epsilon2 allele was also associated with hypertension, elevated serum triglycerides, and total cholesterol. On the other hand, the allele epsilon4 appeared to be associated with increased risk of CAD and was also associated with hypertension, 3-vessel disease, and restenosis. CONCLUSIONS: Accordingly, epsilon4 may be associated with increased risk of CAD, whereas epsilon2 appears to be a predictor of several risk factors for atherosclerosis.     

Characterization of lymphocyte beta 2-adrenoceptor signalling in patients with left ventricular volume overload disease

1. Studies using animal experimental models have suggested that the beta2-adrenoceptor is uncoupled in association with alterations in the expression of G-protein-coupled receptor kinases (GRK) 2/3 in heart failure. However, the functional expression of the components of this pathway in human disease has not been fully elucidated yet. In the present study, we evaluated the possibility that the regulation of beta2-adrenoceptor signalling components in patients with left ventricular volume overload (VOL) depends on the severity of the overload. 2. We characterized the lymphocyte GRK 2-6, beta-arrestins 1 and 2, beta2-adrenoceptor expression at the mRNA and protein levels, as well as the activity of adenylyl cyclase, protein kinases (PK) A and PKC in patients with VOL using healthy blood donors as controls. 3. In the patient group, GRK2 mRNA was increased by 61% (P < 0.001), GRK3 was increased by 54% (P < 0.005), GRK5 was increased fivefold (P < 0.001) and the beta-arrestin 2 mRNA was increased by 40% (P < 0.05). These increases were paralleled with a sixfold increase in GRK2, a twofold increase in GRK3 and a 1.3-fold increase in GRK5 protein levels. These changes were associated with a significant decrease in beta2-adrenoceptor mRNA, the basal, catalytic and receptor-mediated activity of adenylyl cyclase and sensitization of the forskolin-stimulated activity towards augmented inhibition by guanylimidodiphosphate. In general, the increase in GRK2 and 5 mRNA exhibited a positive correlation with the gravity of the haemodynamic load, as determined by changes in left ventricular fractional shortening. 4. The results suggest that VOL induces an increase in the expression of lymphocyte beta2-adrenoceptor-specific GRK and beta-arrestin 2 in association with an attenuation in beta2-adrenoceptor levels. It can be speculated that the cardiac circulatory system adapts itself to altered haemodynamic functional demands partly by altering beta2-adrenoceptor signalling.     

Genetic structure of Plasmodium falciparum populations between lowland and highland sites and antimalarial drug resistance in Western Kenya

Human travel to malaria endemic lowlands from epidemic highlands has been shown to increase the risk of malaria infections in the highlands. In order to gain insight on the impact of human travel, we examined prevalence, genetic variability and population genetic structure of Plasmodium falciparum in asymptomatic children from one highland site and three surrounding malaria endemic lowland sites in Western Kenya, using multilocus microsatellite genotyping. We further analyzed the frequencies of mutations at the genes conferring resistance to chloroquine and sulfadoxine–pyrimethamine. We found a significant decrease in malaria prevalence in the highland site from 2006 to 2007, 1 year after the introduction of the artemisinin-based combination therapy as first-line treatment for uncomplicated malaria and the scale-up of insecticide-treated bed nets. Population genetic diversity, measured by the number of observed and effective microsatellite alleles and Nei's unbiased genetic diversity, was high and comparable for both highland and lowland populations. Analysis of molecular variance did not detect a significant genetic structure across highland and lowland regions. Similarly, mutations at key antimalarial-resistance codons of the pfcrt, pfmdr1, pfdhfr and pfdhps genes were found at comparable high frequencies in all four sites. High level of gene flow and lack of significant genetic structure in malaria parasites between highland and lowland areas suggest the importance of human travel in shaping parasite population structure.     

Using educational games to promote the seeking of a pharmacist and to teach key medication use messages: Results from an inner city health party

BackgroundLow health literacy affects 80–90 million Americans with low-income, minority populations being more vulnerable to this condition. One method of addressing limited literacy that may be particularly well accepted within vulnerable populations is the use of educational board games in order to emphasize seeking health information from reliable sources such as pharmacists.ObjectiveThe research objective was to determine if the use of educational board games could impact community pharmacy patron intentions to seek pharmacist advice in an urban, minority, economically-disadvantaged population.MethodsFour medication-related educational games were played at an urban community pharmacy under the leadership of pharmacy students in the setting of a health party. Game messages, design, and evaluation processes were uniquely guided by community members' input. A verbally administered questionnaire measured game impact via knowledge and perception questions with responses compared between a non-randomly allocated intervention group and a control group.ResultsNinety-nine adults were included in the intervention (or game) group and 94 adults were in the control group. Game participants were significantly more likely than the control group to indicate they would seek pharmacist medication advice in the future.ConclusionEducational board games played in the setting of a health party can be a fun and effective way to convey selected health messages within an urban, minority, economically disadvantaged population. Community input into game development and layering multiple strategies for overcoming health literacy barriers were essential components of this initiative.     

Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats

The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10?μm with an average zeta potential of ?25.5?mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with C_max, AUC_0→48 and t_1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.     

Preferential existence of death-inducing proteins in the human cardiomyopathic left ventricle

INTRODUCTION: Idiopathic or acquired dilated cardiomyopathy (DCM) is a leading health threat resulting in considerable mortality and serious long-term disability with a substantial economic healthcare expenditure. The purpose of this study was to investigate the modulation of apoptotic signaling genes in human cardiomyopathy. METHODS: Cardiac tissue was obtained from six heart transplant recipients (age = 43 +/- 7 y) with DCM. Equivalent control specimens were taken from six healthy heart donors (age = 33 +/- 4 y). The mRNA expression of death-inducing proteins, the death (DRs) and decoy receptors (DcRs), in the four cardiac chambers was quantified using real time polymerase chain reaction LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). Immunodetectable receptor protein expression was quantified densitometrically. Data were analyzed by analysis of variance and unpaired Student's t-test. RESULTS: In DCM tissues, DR1 mRNA was elevated by 42.7% (P < 0.01) in the left ventricle (LV) and 56.4% (P < 0.001) in the left atrium (LA), while DR2 increased by 112.5% (P < 0.00001) in LV and 45.8% (P < 0.05) in LA. Increase in DR4 was 29.6% (P < 0.01) in LV, 82.5% (P < 0.01) in the right ventricle (RV), 210.8% (P < 0.01) in LA, and 99.1% (P < 0.01) in the right atrium (RA). DR5 was elevated by 66.7% (P < 0.01) in LV, 181.8% (P < 0.005) in LA, and 90.2% (P < 0.05) in RA. DcR1 decreased by 30.8% in LV, 44% (P < 0.05) in LA, and 12.5% in RA; DcR3 by 67.1% (P < 0.0001) in LV, 82.4% (P < 0.0001) in RV, 85.1% (P < 0.0001) in LA, and 84.6% (P < 0.0001) in RA. The trends in mRNA expression were comparable to the changes in protein expression. CONCLUSIONS: Left heart-sided increase of death-inducing proteins in human cardiomyopathy is suggestive of their potential modulatory roles in death-related signaling in the pathogenesis of end-stage myocardial failure.     

Does irrigated urban agriculture influence the transmission of malaria in the city of Kumasi, Ghana?

To verify the possible impact of irrigated urban agriculture on malaria transmission in cities, we studied entomological parameters, self-reported malaria episodes, and household-level data in the city of Kumasi, Ghana. A comparison was made between city locations without irrigated agriculture, city locations with irrigated urban vegetable production, and peri-urban (PU) locations with rain-fed agriculture. In the rainy as well as dry seasons, larvae of Anopheles spp. were identified in the irrigation systems of the urban farms. Night catches revealed significantly higher adult anopheline densities in peri-urban and urban agricultural locations compared to non-agricultural urban locations. Polymerase chain reaction (PCR) analysis of Anopheles gambiae sensu lato revealed that all specimens processed were A. gambiae sensu stricto. The pattern observed in the night catches was consistent with household interviews because significantly more episodes of malaria and subsequent days lost due to illness were reported in peri-urban and urban agricultural locations than in non-agricultural urban locations. In Kumasi, urban agriculture is mainly practised in inland valleys, which might naturally produce more mosquitoes. Therefore more detailed studies, also in other cities with different water sources and irrigation systems, and a better spatial distribution of sites with and without urban agriculture than in Kumasi are needed.     

Deforestation and vectorial capacity of Anopheles gambiae Giles mosquitoes in malaria transmission, Kenya

We investigated the effects of deforestation on microclimates and sporogonic development of Plasmodium falciparum parasites in Anopheles gambiae mosquitoes in an area of the western Kenyan highland prone to malaria epidemics. An. gambiae mosquitoes were fed with P. falciparum-infected blood through membrane feeders. Fed mosquitoes were placed in houses in forested and deforested areas in a highland area (1,500 m above sea level) and monitored for parasite development. Deforested sites had higher temperatures and relative humidities, and the overall infection rate of mosquitoes was increased compared with that in forested sites. Sporozoites appeared on average 1.1 days earlier in deforested areas. Vectorial capacity was estimated to be 77.7% higher in the deforested site than in the forested site. We showed that deforestation changes microclimates, leading to more rapid sporogonic development of P. falciparum and to a marked increase of malaria risk in the western Kenyan highland.