Comparison between the world health organization (WHO) and international society of hypertension (ISH) guidelines for hypertension

The global burden of hypertension remains an unsolved problem, especially in low- and middle-income countries (LMICs). For this reason, clinical practice guidelines containing the latest evidence-based recommendations are crucial in the management of hypertension. It is noteworthy that guidelines simply translated from those of high-income countries (HICs) are not the solution to the problem of hypertension in LMICs. Among the numerous guidelines available, those of the World Health Organisation and the International Society of Hypertension are the latest to be published as of the writing of this article. In this review, we conducted both general and specific comparisons between the recommendations supplied by both guidelines. Differences in aspects of hypertension management such as the timing of antihypertensive initiation, assessment of comorbidities and cardiovascular risk factors, pharmacological therapy selection, and blood pressure target and reassessment are explored. Lastly, the implications of the differences found between the two guidelines in both LMICs and HICs are discussed.

Key messages

• Currently, with low treatment and control rates, hypertension remains a burden in low- and middle-income countries (LMICs).
• The lack of customised guidelines for LMICs cannot be solved simply by adopting guidelines from high-income countries.
• The World Health Organisation (WHO) recently published a clinical guideline for the pharmacological management of hypertension in LMICs. We compare select recommendations from the guidelines to those published by the International Society of Hypertension.

     

Molecular Characterization of β-Thalassemia Mutations Via the Amplification Refractory Mutation System-Polymerase Chain Reaction Method at the North Waziristan Agency,Pakistan

β-Thalassemia (β-thal) is a monogenic disease characterized by mutations on the HBB gene, affecting the production of globin that results in hypochromic and microcytic anemia. The aim of this study was to determine the prevalence of six common β-thal mutations, and their frequency and inheritance pattern in affected populations of North Waziristan Agency, Pakistan. In this study, 130 blood samples from 37 unrelated β-thalassemic families having a minimum of one transfusion-dependent child with β-thal major (β-TM), were retrieved either from the Thalassaemia Centre for Women and Children Hospital Bannu or their home towns situated in Noth Waziristan Agency. All samples were analyzed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) using six allele-specific primers for the presence of the six β-thal mutations common in the Pakistani population. Of the six common mutations, our study demonstrated five HBB mutations comprising HBB: c.27_28insG, HBB: c.92+5G>C, HBB: c.126_129delCTTT, HBB: c.92+1G>T and HBB: c.17_18delCT from the families studied, while mutation HBB: c.47G>A [codon 15 (G>A)] was not detected in any of the studied families. Furthermore, the HBB: c.27_28insG and HBB: c.92+5G>C were noted to be the most common with frequencies of 42.85 and 31.42%, respectively. The findings of the present study may be useful in launching carrier screening and prenatal diagnosis (PND) programs by screening analyzed and other unanalyzed affected families for the possible presence of common mutations through the ARMS-PCR technique that will help to control the disease.     

The metabolic effects of lopinavir/ritonavir in HIV-negative men

BACKGROUND: Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects. METHODS: A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks. RESULTS: On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 +/- 0.15 versus 1.63 +/- 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 +/- 0.04 versus 0.43 +/- 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 +/- 2.6 versus 20 +/- 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography. CONCLUSION: Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.     

Changes in beta 2-adrenoceptor and other signaling proteins produced by chronic administration of 'beta-blockers' in a murine asthma model

BACKGROUND: We have previously reported that chronic treatment with certain 'beta-blockers' reduces airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma. METHODS: Airway resistance was measured using the forced oscillation technique in ovalbulmin-sensitized and ovalbulmin-challenged mice treated with several beta-adrenoceptor (beta-AR) ligands. We used the selective beta 2-AR ligand ICI 118,551 and the preferential beta 1-AR ligand metoprolol to investigate the receptor subtype mediating the beneficial effect. Expression of beta-ARs was evaluated using immunofluorescence. We evaluated several signaling proteins by western blot using lung homogenates, and measured the relaxation of the isolated trachea produced by EP2 and IP receptor agonists. RESULTS: Four findings were associated with the decreased AHR after chronic beta-blocker treatment: (1) the highly selective beta 2-AR antagonist/inverse agonist, ICI 118,551 produced the bronchoprotective effect; (2) beta 2-AR up-regulation resulted from chronic 'beta-blocker' treatment; (3) reduced expression of certain proteins involved in regulating bronchial tone, namely, Gi, phosphodiesterase 4D and phospholipase C-beta 1; and (4) an enhanced bronchodilatory response to prostanoid agonists for the IP and EP2 receptors. CONCLUSIONS: These data suggest that in the murine model of asthma, several compensatory changes associated with either increased bronchodilator signaling or decreased bronchoconstrictive signaling, result from the chronic administration of certain 'beta-blockers'.     

Chromosomal inversions and the reproductive isolation of species

Recent genetic studies have suggested that many genes contribute to differences between closely related species that prevent gene exchange, particularly hybrid male sterility and female species preferences. We have examined the genetic basis of hybrid sterility and female species preferences in Drosophila pseudoobscura and Drosophila persimilis, two occasionally hybridizing North American species. Contrary to findings in other species groups, very few regions of the genome were associated with these characters, and these regions are associated also with fixed arrangement differences (inversions) between these species. From our results, we propose a preliminary genic model whereby inversions may contribute to the speciation process, thereby explaining the abundance of arrangement differences between closely related species that co-occur geographically. We suggest that inversions create linkage groups that cause sterility to persist between hybridizing taxa. The maintenance of this sterility allows the species to persist in the face of gene flow longer than without such inversions, and natural selection will have a greater opportunity to decrease the frequency of interspecies matings.