Postmortem Analyses Unveil the Poor Efficacy of Decontamination, Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study.For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NF-κB) activation and excessive collagen deposition.Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process

Still too far to walk: Literature review of the determinants of delivery service use

BACKGROUND: Skilled attendance at childbirth is crucial for decreasing maternal and neonatal mortality, yet many women in low- and middle-income countries deliver outside of health facilities, without skilled help. The main conceptual framework in this field implicitly looks at home births with complications. We expand this to include "preventive" facility delivery for uncomplicated childbirth, and review the kinds of determinants studied in the literature, their hypothesized mechanisms of action and the typical findings, as well as methodological difficulties encountered. METHODS: We searched PubMed and Ovid databases for reviews and ascertained relevant articles from these and other sources. Twenty determinants identified were grouped under four themes: (1) sociocultural factors, (2) perceived benefit/need of skilled attendance, (3) economic accessibility and (4) physical accessibility. RESULTS: There is ample evidence that higher maternal age, education and household wealth and lower parity increase use, as does urban residence. Facility use in the previous delivery and antenatal care use are also highly predictive of health facility use for the index delivery, though this may be due to confounding by service availability and other factors. Obstetric complications also increase use but are rarely studied. Quality of care is judged to be essential in qualitative studies but is not easily measured in surveys, or without linking facility records with women. Distance to health facilities decreases use, but is also difficult to determine. Challenges in comparing results between studies include differences in methods, context-specificity and the substantial overlap between complex variables. CONCLUSION: Studies of the determinants of skilled attendance concentrate on sociocultural and economic accessibility variables and neglect variables of perceived benefit/need and physical accessibility. To draw valid conclusions, it is important to consider as many influential factors as possible in any analysis of delivery service use. The increasing availability of georeferenced data provides the opportunity to link health facility data with large-scale household data, enabling researchers to explore the influences of distance and service quality

Comparative characterization of Shiga toxin type 2 and subtilase cytotoxin effects on human renal epithelial and endothelial cells grown in monolayer and bilayer conditions

Published: June 23, 2016Postdiarrheal hemolytic uremic syndrome (HUS) affects children under 5 years old and is responsible for the development of acute and chronic renal failure, particularly in Argentina. This pathology is a complication of Shiga toxin (Stx)-producing Escherichia coli infection and renal damage is attributed to Stx types 1 and 2 (Stx1, Stx2) produced by Escherichia coli O157:H7 and many other STEC serotypes. It has been reported the production of Subtilase cytotoxin (SubAB) by non-O157 STEC isolated from cases of childhood diarrhea. Therefore, it is proposed that SubAB may contribute to HUS pathogenesis. The human kidney is the most affected organ because very Stx-sensitive cells express high amounts of biologically active receptor. In this study, we investigated the effects of Stx2 and SubAB on primary cultures of human glomerular endothelial cells (HGEC) and on a human tubular epithelial cell line (HK-2) in monoculture and coculture conditions. We have established the coculture as a human renal proximal tubule model to study water absorption and cytotoxicity in the presence of Stx2 and SubAB. We obtained and characterized cocultures of HGEC and HK-2. Under basal conditions, HGEC monolayers exhibited the lowest electrical resistance (TEER) and the highest water permeability, while the HGEC/HK-2 bilayers showed the highest TEER and the lowest water permeability. In addition, at times as short as 20-30 minutes, Stx2 and SubAB caused the inhibition of water absorption across HK-2 and HGEC monolayers and this effect was not related to a decrease in cell viability. However, toxins did not have inhibitory effects on water movement across HGEC/HK-2 bilayers. After 72 h, Stx2 inhibited the cell viability of HGEC and HK-2 monolayers, but these effects were attenuated in HGEC/HK-2 bilayers. On the other hand, SubAB cytotoxicity shows a tendency to be attenuated by the bilayers. Our data provide evidence about the different effects of these toxins on the bilayers respect to the monolayers. This in vitro model of communication between human renal microvascular endothelial cells and human proximal tubular epithelial cells is a representative model of the human proximal tubule to study the effects of Stx2 and SubAB related to the development of HUS.Romina S. Álvarez, Flavia Sacerdoti, Carolina Jancic, Adrienne W. Paton, James C. Paton, Cristina Ibarra, María M. Amara