The synthesis of a novel thromboxane receptor antagonist 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid ICI 192605

The synthesis and summary pharmacology of a novel thromboxane receptor antagonist 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1, 3-dioxan-cis-5-yl) hexenoic acid (3) is reported. Compound 3 was competitive and selective with pA2 values of 8.0 +/- 0.1 (rabbit) and 8.4 +/- 0.05 (rat) on smooth muscle preparations and 8.16 +/- 0.01 on human platelets. In vivo activity of 3 was demonstrated in a Konzett Rossler guinea pig model at 0.01 mg/kg p.o.     

<Emphasis Type="Italic">Phylo-mLogo</Emphasis>: an interactive and hierarchical multiple-logo visualization tool for alignment of many sequences

Background  

When aligning several hundreds or thousands of sequences, such as epidemic virus sequences or homologous/orthologous sequences of some big gene families, to reconstruct the epidemiological history or their phylogenies, how to analyze and visualize the alignment results of many sequences has become a new challenge for computational biologists. Although there are several tools available for visualization of very long sequence alignments, few of them are applicable to the alignments of many sequences.     

Cardiovascular Health and Related Health Care Use of Moluccan-Dutch Immigrants

Objective

Studies regularly show a higher incidence, prevalence and mortality of cardiovascular disease among immigrant groups from low-income countries. Despite residing in the Netherlands for over 60 years, the Moluccan-Dutch cardiovascular disease profile and health care use are still unknown. We aimed to compare (a) the clinical prevalence of cardiovascular diseases and (b) the use of health care services by cardiovascular disease patients of 5,532 Moluccan-Dutch to an age-sex matched control group of 55,320 native Dutch.

Methods

We performed a cross-sectional analysis of data of the Achmea health insurance company for the period of 1 January 2009 to 31 December 2010. We collected information on health care use, including diagnostic information. Linear and logistic regression models were used for comparison.

Results

Moluccans had a higher clinical prevalence of ischemic heart diseases (odds ratio 1.26; 95% confidence interval 1.03–1.56), but tended to have a lower prevalence of cerebrovascular accidents (0.79; 0.56–1.11) and cardiac failure (0.67; 0.44–1.03). The clinical prevalence of cardiovascular diseases together tended to be lower among Moluccans (0.90; 0.80–1.00). Consultation of medical specialists did not differ. Angiotensin II inhibitors (1.42; 1.09–1.84), antiplatelet agents (1.27; 1.01–1.59) and statins (1.27; 1.00–1.60) were prescribed more frequently to Moluccans, as were cardiovascular agents in general (1.27; 0.94–1.71).

Conclusion

The experience of Moluccans in the Netherlands suggests that, in the long run, cardiovascular risk and related health care use of ethnic minority groups may converge towards that of the majority population.     

Hypertension in sub-Saharan Africa: cross-sectional surveys in four rural and urban communities

Background

Cardiovascular disease (CVD) is the leading cause of adult mortality in low-income countries but data on the prevalence of cardiovascular risk factors such as hypertension are scarce, especially in sub-Saharan Africa (SSA). This study aims to assess the prevalence of hypertension and determinants of blood pressure in four SSA populations in rural Nigeria and Kenya, and urban Namibia and Tanzania.

Methods and Findings

We performed four cross-sectional household surveys in Kwara State, Nigeria; Nandi district, Kenya; Dar es Salaam, Tanzania and Greater Windhoek, Namibia, between 2009–2011. Representative population-based samples were drawn in Nigeria and Namibia. The Kenya and Tanzania study populations consisted of specific target groups. Within a final sample size of 5,500 households, 9,857 non-pregnant adults were eligible for analysis on hypertension. Of those, 7,568 respondents ≥18 years were included. The primary outcome measure was the prevalence of hypertension in each of the populations under study.The age-standardized prevalence of hypertension was 19.3% (95%CI:17.3–21.3) in rural Nigeria, 21.4% (19.8–23.0) in rural Kenya, 23.7% (21.3–26.2) in urban Tanzania, and 38.0% (35.9–40.1) in urban Namibia. In individuals with hypertension, the proportion of grade 2 (≥160/100 mmHg) or grade 3 hypertension (≥180/110 mmHg) ranged from 29.2% (Namibia) to 43.3% (Nigeria). Control of hypertension ranged from 2.6% in Kenya to 17.8% in Namibia. Obesity prevalence (BMI ≥30) ranged from 6.1% (Nigeria) to 17.4% (Tanzania) and together with age and gender, BMI independently predicted blood pressure level in all study populations. Diabetes prevalence ranged from 2.1% (Namibia) to 3.7% (Tanzania).

Conclusion

Hypertension was the most frequently observed risk factor for CVD in both urban and rural communities in SSA and will contribute to the growing burden of CVD in SSA. Low levels of control of hypertension are alarming. Strengthening of health care systems in SSA to contain the emerging epidemic of CVD is urgently needed.     

Enhancing ascorbate in fruits and tubers through over-expression of the L-galactose pathway gene GDP-L-galactose phosphorylase

Ascorbate, or vitamin C, is obtained by humans mostly from plant sources. Various approaches have been made to increase ascorbate in plants by transgenic means. Most of these attempts have involved leaf material from model plants, with little success reported using genes from the generally accepted l-galactose pathway of ascorbate biosynthesis. We focused on increasing ascorbate in commercially significant edible plant organs using a gene, GDP-l-galactose phosphorylase (GGP or VTC2), that we had previously shown to increase ascorbate concentration in tobacco and Arabidopsis thaliana. The coding sequence of Actinidia chinensis GGP, under the control of the 35S promoter, was expressed in tomato and strawberry. Potato was transformed with potato or Arabidopsis GGP genes under the control of the 35S promoter or a polyubiquitin promoter (potato only). Five lines of tomato, up to nine lines of potato, and eight lines of strawberry were regenerated for each construct. Three lines of tomato had a threefold to sixfold increase in fruit ascorbate, and all lines of strawberry showed a twofold increase. All but one line of each potato construct also showed an increase in tuber ascorbate of up to threefold. Interestingly, in tomato fruit, increased ascorbate was associated with loss of seed and the jelly of locular tissue surrounding the seed which was not seen in strawberry. In both strawberry and tomato, an increase in polyphenolic content was associated with increased ascorbate. These results show that GGP can be used to raise significantly ascorbate concentration in commercially significant edible crops.     

Isolation and concentration of Salmonellae with an immunoaffinity column

A method for rapidly and selectively isolating Salmonellae from buffer solutions and concentrating the bacteria by a factor of approximately 500 was developed. Anti-Salmonellae antibody was covalently linked to 40 microm polyacrylamide beads to prepare a solid phase with affinity for the bacteria. The beads were packed into 1-mm diameter glass tubes to form a column 20 microl in volume. Buffer containing Salmonellae at concentrations ranging from 10(2) to 10(6)/ml was pumped through the column to trap and concentrate the bacteria. At a flow rate of 50 microl/min, more than 95% of the bacteria introduced to the column were captured, while at 800 microl/min capture dropped to 32%. Specificity was high, with no detectable capture of Escherichia coli at a concentration of 10(5)/ml. Capture of more than 90% of Salmonellae in a 5-ml sample was achieved in 40 min by re-circulating the sample through the column at a flow rate of 500 microl/.     

Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline

Background  

Differential methylation of the two alleles is a hallmark of imprinted genes. Correspondingly, loss of DNA methyltransferase function results in aberrant imprinting and abnormal post-fertilization development. In the mouse, mutations of the oocyte-specific isoform of the DNA methyltransferase Dnmt1 (Dnmt1o) and of the methyltransferase-like Dnmt3L gene result in specific failures of imprint establishment or maintenance, at multiple loci. We have previously shown in humans that an analogous inherited failure to establish imprinting at multiple loci in the female germline underlies a rare phenotype of recurrent hydatidiform mole.     

Fractal ventilation enhances respiratory sinus arrhythmia

Background

Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise) improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA) – a mechanism known to improve ventilation/perfusion matching.

Methods

Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV) or in fractal mode (FV) at baseline and then following infusion of oleic acid to result in lung injury.

Results

Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043); post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028); at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047); post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026). Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively.

Conclusion

These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV.