Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient’s values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.
Hypertension is the leading remediable risk factor for cardiovascular disease, affecting more than 1 billion people worldwide, and is responsible for more than 10 million preventable deaths globally each year. While hypertension can be successfully diagnosed and treated, only one in seven persons with hypertension have controlled blood pressure. To meet the challenge of improving the control of hypertension, particularly in low- and middle-income countries, the authors developed the Standardized Hypertension Treatment and Prevention Project, which involves a health systems–strengthening approach that advocates for standardized hypertension management using evidence-based interventions. These interventions include the use of standardized treatment protocols, a core set of medications along with improved procurement mechanisms to increase the availability and affordability of these medications, registries for cohort monitoring and evaluation, patient empowerment, team-based care (task shifting), and community engagement. With political will and strong partnerships, this approach provides the groundwork to reduce high blood pressure and cardiovascular disease-related morbidity and mortality.
Scope-Diabetic embryopathy, a consequence of diabetic pregnancy is associated with increase in embryonic oxidative stress and apoptosis which lead to severe embryonic damage at early stage of organogenesis.Methods and results-This study investigated if resveratrol, found in red grapes and blueberries, may prevent diabetes-induced oxidative stress and apoptosis in embryos and have beneficial effects in diabetic dams. A rodent model of diabetic embryopathy was used. Diabetes was associated with lowered reduced glutathione levels (26.98%), increased total thiol (100.47%) and lipid peroxidation (124.73%) in embryos, and increased blood sugar (384.03%), cholesterol (98.39%) and triglyceride (1025.35%) in diabetic dams. Increased apoptosis (272.20%) was also observed in the embryos of diabetic dams. Administration of resveratrol (100 mg/kg b. wt.) during pregnancy prevented both oxidative stress and apoptosis in embryos. Resveratrol reduced embryonic maldevelopment by improving embryo weight (41.23%), crown rump length (16.50%) and somite number (11.22%). It further improved the glucose (33.32%) and lipid (cholesterol 41.74%, triglyceride 60.64%) profile of the diabetic dams which also represents the protective role of resveratrol in diabetes.Conclusion-Resveratrol was found to prevent embryonic oxidative stress and apoptosis. It also improved glucose and lipid profile of diabetic dams indicating the beneficial effects in diabetic pregnancy.
The role of sensory innervation in the regulation of liver physiology and the pathogenesis of cholestatic liver disease are undefined. Biliary proliferation has been shown to be coordinately controlled by parasympathetic and sympathetic innervation of the liver. The aim of our study was to address the role of the sensory neuropeptide calcitonin gene-related peptide (a-CGRP) in the regulation of cholangiocyte proliferation during cholestasis induced by extrahepatic bile duct obstruction (BDL). Our study utilized a knockout (KO) mouse model, which lacks the sensory neuropeptide a-CGRP. Wildtype (WT) and a-CGRP KO mice were subjected to sham surgery or BDL for 3 and 7 days. In addition, immediately after BDL, WT and KO mice were administered the CGRP receptor antagonist (CGRP 8-37 ) for 3 and 7 days by osmotic minipumps. Liver sections and isolated cholangiocytes were evaluated for proliferation markers. Isolated WT BDL (3 days) cholangiocytes were stimulated with a-and b-CGRP and evaluated for proliferation and cAMP-mediated signaling. Lack of a-CGRP inhibits cholangiocyte proliferation induced by BDL at both 3 and 7 days. BDL-induced cholangiocyte proliferation in WT mice was associated with increases of circulating a-CGRP levels. In vitro, a-and b-CGRP stimulated proliferation in purified BDL cholangiocytes, induced elevation of cAMP levels, and stimulated the activation of cAMPdependent protein kinase A and cAMP response element binding protein DNA binding. In conclusion, sensory innervation of the liver and biliary expression of a-CGRP play an important role in the regulation of cholangiocyte proliferation during cholestasis.
Abstract-Nerves that contain calcitonin gene-related peptide (CGRP) are components of the sensory nervous system.Although these afferent nerves have traditionally been thought to sense stimuli in the periphery and transmit the information centrally, they also have an efferent vasodilator function. Acute administration of a CGRP receptor antagonist increases the blood pressure (BP) in several models of hypertension, which indicates that this potent vasodilator plays a counterregulatory role to attenuate the BP increase in these settings. To determine the role of this peptide in the long-term regulation of cardiovascular function, including hypertension, we obtained mice that have a deletion of the ␣-calcitonin gene-related peptide (␣-CGRP) gene. Although the -calcitonin gene-related peptide (-CGRP) gene is intact in these mice, ␣-CGRP is by far the predominant species of CGRP produced in dorsal root ganglia (DRG) sensory neurons. Initially, we examined the effect of deletion of the ␣-CGRP on baseline BP and -CGRP and substance P mRNA expression. Systolic BP was significantly higher in the knockout mice (nϭ7) compared with wild-type in both male (160Ϯ6.1 vs 125Ϯ4.8 mm Hg) and female (163Ϯ4.8 vs 135Ϯ33 mm Hg) mice. Next, groups (nϭ7) of knockout and wild-type mice had catheters surgically placed in the right carotid artery for mean arterial pressure recording. With the animals fully awake and unrestrained, the knockout mice displayed an elevated mean arterial pressure compared with wild-type in both male (139Ϯ4.9 vs 118Ϯ4.9 mm Hg) and female (121Ϯ3.4 vs 107Ϯ3.1 mm Hg) mice. Northern blot analysis of DRG RNA samples confirmed the absence of ␣-CGRP mRNA in the knockout mice. Substance P mRNA content in DRG was unchanged between the 2 groups; however, -CGRP mRNA levels were reduced 2-fold in the knockout mice. These results indicate for the first time that ␣-CGRP may be involved in the long-term regulation of resting BP and suggest that these mice are particularly sensitive to challenges to BP homeostasis because of the loss of a compensatory vasodilator mechanism. Key Words: peptides Ⅲ blood pressure Ⅲ mice Ⅲ genes C alcitonin gene-related peptide (CGRP) is a 37-amino acid vasoactive neuropeptide that is widely distributed in the central and peripheral nervous systems in mammals. 1,2 ␣-CGRP is produced by the tissue-specific alternative splicing of the primary transcript of the calcitonin/␣-CGRP gene and is synthesized almost exclusively in neuronal tissues. 3,4 There is a second CGRP gene, -CGRP, which does not produce calcitonin. 5 Again, expression of -CGRP is limited almost exclusively to specific neuronal sites. 4,5 The 2 CGRP genes, ␣ and  in the rat and I and II in humans, differ in their protein sequences by 1 and 3 amino acids, respectively, and their biological activities are quite similar in most vascular beds. 6,7 The dorsal root ganglia (DRG) is a prominent site of CGRP synthesis that contains the cell bodies of primary afferent neurons that terminate peripherally on blood vessels and other tissue...
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