Maternal mortality: levels, causes and promising interventions

About two-thirds of the world's population live in areas where registration of vital statistics is unsatisfactory (Tietze, 1977), and in many countries such statistics from rural areas are unavailable or grossly underestimated (WHO, 1971). Most of the women who die in pregnancy and childbirth are poor and live in remote areas or city slums. Their deaths are accorded little importance and fail to enter register

Acute depression of mitochondrial protein synthesis during anoxia: Contributions of oxygen sensing, matrix acidification, and redox state

Mitochondrial protein synthesis is acutely depressed during anoxia-induced quiescence in embryos of Artemia franciscana. Oxygen deprivation is accompanied in vivo by a dramatic drop in extramitochondrial pH, and both of these alterations strongly inhibit protein synthesis in isolated mitochondria. Here we show that the oxygen dependence is not explained simply by blockage of the electron transport chain or by the increased redox state. Whereas oxygen deprivation substantially depressed protein synthesis within 5 min and resulted in a 77% reduction after 1 h, aerobic incubations with saturating concentrations of cyanide or antimycin A had little effect during the first 20 min and only a modest effect after 1 h (36 and 20% reductions, respectively). Yet the mitochondrial NAD(P)H pools were fully reduced after 2-3 min with all three treatments. This cyanide- and antimycin-insensitive but hypoxia-sensitive pattern of protein synthesis depression suggests the presence of a molecular oxygen sensor within the mitochondrion. Second, we show for the first time that acidification of extramitochondrial pH exerts inhibition on protein synthesis specifically through changes in matrix pH. Matrix pH was 8.2 during protein synthesis assays performed at the extramitochondrial pH optimum of 7.5. When this proton gradient was abolished with nigericin, the extramitochondrial pH optimum for protein synthesis displayed an alkaline shift of ∼0.7 pH unit. These data suggest the presence of proton-sensitive translational components within the mitochondrion

Comparison of the transcriptomic "stress response" evoked by antimycin A and oxygen deprivation in saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Acute changes in environmental parameters (e.g., O₂, pH, UV, osmolarity, nutrients, etc.) evoke a common transcriptomic response in yeast referred to as the "environmental stress response" (ESR) or "common environmental response" (CER). Why such a diverse array of insults should elicit a common transcriptional response remains enigmatic. Previous functional analyses of the networks involved have found that, in addition to up-regulating those for mitigating the specific stressor, the majority appear to be involved in balancing energetic supply and demand and modulating progression through the cell cycle. Here we compared functional and regulatory aspects of the stress responses elicited by the acute inhibition of respiration with antimycin A and oxygen deprivation under catabolite non-repressed (galactose) conditions.</p> <p>Results</p> <p>Gene network analyses of the transcriptomic responses revealed both treatments result in the transient (10 – 60 min) down-regulation of MBF- and SBF-regulated networks involved in the G1/S transition of the cell cycle as well as Fhl1 and PAC/RRPE-associated networks involved in energetically costly programs of ribosomal biogenesis and protein synthesis. Simultaneously, Msn2/4 networks involved in hexose import/dissimilation, reserve energy regulation, and autophagy were transiently up-regulated. Interestingly, when cells were treated with antimycin A well before experiencing anaerobiosis these networks subsequently failed to respond to oxygen deprivation. These results suggest the transient stress response is elicited by the acute inhibition of respiration and, we postulate, changes in cellular energetics and/or the instantaneous growth rate, not oxygen deprivation <it>per se</it>. After a considerable delay (≥ 1 generation) under anoxia, predictable changes in heme-regulated gene networks (e.g., Hap1, Hap2/3/4/5, Mot3, Rox1 and Upc2) were observed both in the presence and absence of antimycin A.</p> <p>Conclusion</p> <p>This study not only differentiates between the gene networks that respond to respiratory inhibition and those that respond to oxygen deprivation but suggests the function of the ESR or CER is to balance energetic supply/demand and coordinate growth with the cell cycle, whether in response to perturbations that disrupt catabolic pathways or those that require rapidly up-regulating energetically costly programs for combating specific stressors.</p

Oxidative phosphorylation and the realkalinization of intracellular pH during recovery from anoxia in Artemia franciscana embryos

The contribution of mitochondrial oxidative phosphorylation to the realkalinization of intracellular pH (pHi) and resynthesis of purine nucleotides during recovery from anoxia was investigated in embryos of Artemia franciscana by assessing the sensitivity of mitochondrial respiration to pH, calculating proton consumption by oxidative phosphorylation, and measuring changes in pHi using 31P nuclear magnetic resonance. Following short-term anoxia, pHi increased from 6.7 to 7.7 during 20 min of aerobic recovery and was temporally correlated with a large increase in ATP. State 3 respiration rates of isolated mitochondria were not substantially compromised at the acidic pH corresponding to the pHi during anoxia (pH 6.3-6.8) compared to values obtained at pH 7.7. Both state 3 respiration rates and respiratory control ratios exhibited broad, substrate-specific pH optima, whereas state 4 respiration rates increased gradually with increasing pH. P:O flux ratios were near their mechanistic limits and did not vary appreciably with pH below 7.5. Estimates of intracellular buffering capacity indicate that between 18 and 37 mmol H+ (1 cytosol)-1 must be consumed to elevate pHi from 6.7 to 7.7. Phosphorylation of mono- and diphosphate purine-nucleotides during the first 20 min of recovery may account for the consumption of up to 4.79 mmol H+ (1 cytosol)-1. An additional 4.77 to 8.18 mmol H+ (1 cytosol)-1 may be consumed through the oxidation of mono- or dicarboxylic acids, respectively, in the Krebs cycle. Taken together, these data are consistent with a role for oxidative phosphorylation in the realkalinization of pHi and resynthesis of purine nucleotides in A. franciscana embryos during recovery from anoxia. © 1995

A narrative review

Funding Information: Acknowledgement: RB is supported by FCT (2022.13386.BD). Publisher Copyright: © 2024 Canadian Urological Association. All rights reserved.The interest in broadening the application of active surveillance (AS) has been increasing, encompassing patients who may not strictly adhere to the conventional criteria for low-risk prostate cancer (PCa), particularly those diagnosed with small-volume Gleason grade group 2 disease. Nonetheless, accurately identifying individuals with low-intermediate risk PCa who can safely undergo AS without facing disease progression remains a challenge. This review aims to delve into the progression of this evolving trend specifically within this cohort of men, while also examining strategies aimed at minimizing irreversible disease advancement. Additionally, we address the criteria for patient selection, recommended followup schedules, and the indicators prompting intervention.proofpublishe

Modulation of intra-epithelial expansion of human T24 bladder-carcinoma cells in murine urothelium by growth factors and extracellular-matrix components

The high recurrence rate of bladder cancer is probably due to an efficient repopulation of the bladder by residual transformed cells after resection of the tumour. However, the regenerating capacity of the normal urothelial cells is very high. To study the balance between regenerating normal urothelium and outgrowth of transformed urothelial cells, we recently developed an in vitro co-cultivation model. With this model system we studied the effects of growth factors and extracellular-matrix components on the intra-epithelial expansion of human T24 bladder-carcinoma cells in primary mouse-bladder explants. Exposure of the cultures to acidic fibroblast growth factor (aFGF) and laminin led to a dramatic increase in the number of invasive T24 cells into the primary urothelium. Epidermal growth factor (EGF) and collagen types I and IV counteracted the infiltration of individual T24 cells. EGF, aFGF, laminin and collagen types I and IV did not directly affect the migration and proliferation of T24 cells. Apparently, the efficacy of invasion of transformed urothelial cells into primary urothelium is not only dependent on the intrinsic characteristics of the transformed cells, but can be influenced to a considerable extent by exogenous components exerting their influence on the normal urothelium. The clinical relevance of this observation needs to be studied further

Increasing trend of utilising active surveillance for Gleason Score 7 (3 + 4) prostate cancer

Funding Information: None Rui Bernardino is supported by FCT (2022.13386.BD).publishersversionpublishe

Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels

Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion