Hypertension in Hypoxia
An overview of blood pressure regulation in hypoxia addresses altitude physiology, sleep disordered breathing, and cardiopulmonary disease. It reviews pathophysiology and therapeutic implications.
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An overview of blood pressure regulation in hypoxia addresses altitude physiology, sleep disordered breathing, and cardiopulmonary disease. It reviews pathophysiology and therapeutic implications.
Introduction Congenital Heart Defects (CHDs) are structural abnormalities of the heart and intra-thoracic great vessels that are present at birth and may be of functional significance. They are the most frequently occurring congenital anomalies and babies born with severe forms of these defects are likely to die in the neonatal period. Objectives The aim of this study was to determine the prevalence of CHDs among neonates delivered in Port Harcourt, Rivers State, Nigeria Methods Using a stratified sampling technique, 530 neonates were selected from three hospitals in Port Harcourt. The biodata of the parents and socio-demographic information were obtained through an interviewer-administered questionnaire to the mothers. Physical examination and echocardiograghy were performed on all the neonates. Results Five hundred and thirty (530) neonates aged 0-7days (5.2±1.8) participated in this study and the male to female ratio was 1.1:1. Forty-three neonates were found to have CHD giving a prevalence of 8.1% 95%CI: 6.0. Thirty-nine were acyanotic and four cyanotic. Congenital Heart Defects were found in 21 (48.8%) males and 22 (51.2%) females. The more common heart defects were isolated Atrial Septal Defect in 16(37.2%), isolated Patent Ductus Arteriosus in 11(25.6%) and isolated Ventricular Septal Defect in 6 (13.9%). The most common cyanotic CHD was Transposition of the Great Arteries in 2 neonates (4.7%). The clinical features identified in neonates with CHD were tachypnoea, dysmorphia, cyanosis, hypoxia and murmur Conclusion The prevalence of CHD is considerably high in Port Harcourt and further studies need to be carried out to ascertain the risk factors.
Pyruvate holds superior biomedical properties in increase of hypoxia tolerance, correction of severe acidosis, exertion of anti-oxidative stress and protection of mitochondria against apoptosis, so that it improves multi-organ function in various pathogenic insults. Particularly, pyruvate preserves key enzyme: pyruvate dehydrogenase (PDH) activity through direct inhibition of pyruvate dehydrogenase kinas (PDK), as a PDH activator, in hypoxia. Therefore, pyruvate is robustly beneficial for cell/organ function over citrate, acetate, lactate, bicarbonate and chloride as anions in current medical fluids. Pyruvate-enriched oral rehydration salt/solution (Pyr-ORS) and pyruvate-based intravenous (IV) fluids would be more beneficial than WHO-ORS and current IV fluids in both crystalloids and colloids, respectively. Pyruvate-containing fluids as the new generation would be not only a volume expander, but also a therapeutic agent simultaneously in fluid resuscitation in critical care patients. Pyruvate may be also beneficial in prevent and treatment of diabetes, aging and even cancer. Pyruvate clinical applications indicates a new revolutionary medical advance, following the WHO-ORS prevalence, this century.
The paper explores the formation of a-oxoaldehydes during the interaction of glucose metabolites with hydroxyl or alkoxyl radicals. Hydroxyl radicals were generated under radiolysis of aqueous solutions, and alkoxyl radicals (t-BuO) were obtained in the model system tert-butyl hydroperoxide/Fe2+. High-performance liquid chromatography revealed that methylglyoxal was one of the organic products resulting from t-BuO-induced transformations of fructose-1,6-bisphosphate under hypoxic conditions. The interaction of lysine and methylglyoxal one of the main targets of a-oxoaldehydes in proteins was also studied. As chemiluminescence and EPR spectroscopy demonstrated, this reaction generates a methylglyoxal anion radical, a cation-radical of methylglyoxal dialkylamine and a superoxide anion radical. EPR signal of methylglyoxal-derived free radicals was observed in hypoxia, whereas only the trace amounts of these free radicals were recorded in the aerated reaction medium.
Renal fibrosis was a chronic and progressive process affecting kidneys in chronic kidney disease (CKD), regardless of cause. Although no effective targeted therapy yet existed to retard renal fibrosis, a number of important recent advances have highlighted the cellular and molecular mechanisms underlying the renal fibrosis. The advances including TGF-β/Smad pathway, oxidative stress and inflammation, hypoxia and gut microbiota-derived from uremic solutes were highlighted that could provide therapeutic targets. New therapeutic targets and strategies that are particularly promising for development of new treatments for patients with CKD were also highlighted.
Purpose The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) gene which encodes hypoxia-inducible-factor-2 alpha (HIF2a) is a transcription factor that is involved in the response to hypoxia. EPAS1 has been found to have four (rs56721780, rs6756667, rs7589621, rs1868092) simple nucleotide polymorphisms (SNPs) associated with human disease.These SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to disease and alterations in high altitude adaptation in humans. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theEPAS1 gene from 1.6 kb upstream of the transcriptional start site to 539 bps past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The EPAS1 SNPs in the promoter, intron two and the 3’UTR regions have previously been found to be significantly associated with disease and different levels of high-altitude hypoxia among native Tibetans. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the EPAS1 genesuch as for the glucocorticoid and mineralocorticoid nuclear receptor binding sites created by the rs7589621 rSNP EPAS1-G allele. These receptors regulate carbohydrate, protein and fat metabolism. Also the minor rs7589621 rSNP EPAS1-A creates a punitive TFBS for the FOXC TF which is an important regulator of cell viability and resistance to oxidative stress. These EPAS1 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF EPAS1 regulation. The punitive changes in TFBS created by the four rSNPs could very well influence the significant cline in allele frequencies seen in Tibetans with increasing altitude or the haplotype association with high altitude polycythemia in male Han Chinese. These regulatory changes were discussed with respect to changes in human health that result in disease and sickness.