Are Anti-Beta2-Glycoprotein-I Antibodies Markers for Recurrent Pregnancy Loss in Lupus Anticoagulant/Anticardiolipin Seronegative Women?

Problem  Anti-beta₂-Glicoprotein-1 antibodies (anti-β₂GPI-ab) have been related to recurrent miscarriage (RM) with conflicting results. The aim was to evaluate the role of anti-β₂-GPI-ab as unique biological marker in RM related to antiphospholipid (aPL).
Method of study  A cohort study that included 59 cases, divided in two groups, was designed: group 1 comprised 43 pregnant women with 'obstetric' antiphospholipid syndrome (APS) and group 2 included 16 cases with similar complaints but only having repeatedly anti-β₂-GPI-ab. Previous thrombosis and/or inherited thrombophilia were excluded. Lupus anticoagulant, anticardiolipin antibodies (aCA), anti-β₂-GPI-ab, and other autoantibodies were analyzed. Miscarriages, premature births, pre-eclampsia, live births, placental and systemic thromboses were studied.
Results  No differences in previous obstetric complications were detected ( P  =   1.00–0.164). After the treatment, differences in number of obstetric complications were not seen ( P  =   1.00). Live births were similar in two groups (88.4% and 93.7%; P  =   1.00). Placental thrombosis was equal in both groups, 93.3% versus 80% ( P  =   1.00).
Conclusion  These results suggest that anti-β₂-GPI-ab may be considered a biological marker for obstetric APS.     

Prospective adverse event risk evaluation in clinical trials

Health Care Management Science - Proactive and objective regulatory risk management of ongoing clinical trials is limited, especially when it involves the safety of the trial. We seek to...     

The apicomplexan parasite Eimeria arloingi induces caprine neutrophil extracellular traps

As a novel effector mechanism polymorphonuclear neutrophils (PMN) release neutrophil extracellular traps (NETs), which represent protein-labeled DNA matrices capable of extracellular trapping and killing of invasive pathogens. Here, we demonstrate for the first time NET formation performed by caprine PMN exposed to different stages (sporozoites and oocysts) of the goat apicomplexan protozoan parasite Eimeria arloingi. Scanning electron microscopy as well as fluorescence microscopy of sporozoites- and oocysts-PMN co-cultures revealed a fine network of DNA fibrils partially covering the parasites. Immunofluorescence analyses confirmed the co-localization of histones (H3), neutrophil elastase (NE), and myeloperoxidase (MPO) in extracellular traps released from caprine PMN. In addition, the enzymatic activity of NE was found significantly enhanced in sporozoite-exposed caprine PMN. The treatment of caprine NET structures with deoxyribonuclease (DNase) and the NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced NETosis confirming the classical characteristics of NETs. Caprine NETs efficiently trapped vital sporozoites of E. arloingi since 72 % of these stages were immobilized—but not killed—in NET structures. As a consequence, early infection rates were significantly reduced when PMN-pre-exposed sporozoites were allowed to infect adequate host cells. These findings suggest that NETs may play an important role in the early innate host response to E. arloingi infection in goats.     

Bypassing primary care clinics for childbirth: a cross-sectional study in the Pwani region,United Republic of Tanzania

Objective

To measure the extent, determinants and results of bypassing local primary care clinics for childbirth among women in rural parts of the United Republic of Tanzania.

Methods

Women were selected in 2012 to complete a structured interview from a full census of all 30 076 households in clinic catchment areas in Pwani region. Eligibility was limited to those who had delivered between 6 weeks and 1 year before the interview, were at least 15 years old and lived within the catchment areas. Demographic and delivery care information and opinions on the quality of obstetric care were collected through interviews. Clinic characteristics were collected from staff via questionnaires. Determinants of bypassing (i.e. delivery of the youngest child at a health centre or hospital without provider referral) were analysed using multivariate logistic regression. Bypasser and non-bypasser birth experiences were compared in bivariate analyses.

Findings

Of 3019 eligible women interviewed (93% response rate), 71.0% (2144) delivered in a health facility; 41.8% (794) were bypassers. Bypassing likelihood increased with primiparity (odds ratio, OR: 2.5; 95% confidence interval, CI: 1.9–3.3) and perceived poor quality at clinics (OR: 1.3; 95% CI: 1.0–1.7) and decreased if clinics recently underwent renovations (OR: 0.39; 95% CI: 0.18–0.84) and/or performed ≥ 4 obstetric signal functions (OR: 0.19; 95% CI: 0.08–0.41). Bypassers reported better quality of care on six of seven quality of care measures.

Conclusion

Many pregnant women, especially first-time mothers, choose to bypass local primary care clinics for childbirth. Perceived poor quality of care at clinics was an important reason for bypassing. Primary care is failing to meet the obstetric needs of many women in this rural, low-income setting.     

Nonselective cation channels as effectors of free radical-induced rat liver cell necrosis

Necrosis, as opposed to apoptosis, is recognized as a nonspecific cell death that induces tissue inflammation and is preceded by cell edema. In non-neuronal cells, the latter has been explained by defective outward pumping of Na(+) caused by metabolic depletion or by increased Na(+) influx via membrane transporters. Here we describe a novel mechanism of swelling and necrosis; namely the influx of Na(+) through oxidative stress-activated nonselective cation channels. Exposure of liver epithelial Clone 9 cells to the free-radical donors calphostin C or menadione induced the rapid activation of an approximately 16-pS nonselective cation channel (NSCC). Blockage of this conductance with flufenamic acid protected the cells against swelling, calcium overload, and necrosis. Protection was also achieved by Gd(3+), an inhibitor of stretch-activated cation channels, or by isosmotic replacement of extracellular Na(+) with N-methyl-D-glucamine. It is proposed that NSCCs, which are ubiquitous although largely inactive in healthy cells, become activated under severe oxidative stress. The ensuing influx of Na(+) initiates a positive feedback of metabolic and electrolytic disturbances leading cells to their necrotic demise.     

Sorting functions of the individual cytoplasmic domains of the G protein-coupled vasopressin V(2) receptor in Madin Darby canine kidney epithelial cells

Previous studies have shown that the G protein-coupled human vasopressin V(2) receptor (V(2) receptor) is expressed predominantly in the basolateral membrane of Madin Darby canine kidney type II (MDCKII) epithelial cells at steady state. Here we have assessed the influence of the individual cytoplasmic domains of the V(2) receptor on polarized sorting in MDCKII cells. The second (ICL2) and third (ICL3) intracellular loops and the C-terminal tail were fused separately to a green fluorescent protein-tagged receptor fragment comprising the first transmembrane domain and flanking regions. We show that the ICL2 domain of the V(2) receptor alone promotes basolateral cell surface expression and thus seems to contain the basolateral sorting signal of the V(2) receptor. Fusion of the other cytoplasmic domains, however, does not lead to a randomized cell surface expression. The C-terminal tail of the V(2) receptor promotes apical targeting. Fusion of ICL3 leads to a receptor fragment that is retained in the endoplasmic reticulum (ER). The results are consistent with a model in which the V(2) receptor contains signals for both apical and basolateral cell surface expression, the latter being dominant. Furthermore, ICL3 may contain a RXR [corrected] ER retention signal, which is not accessible in the correctly folded full-length receptor but which is unmasked when ICL3 is fused alone.     

Molecular and conformational features of a transport-relevant domain in the C-terminal tail of the vasopressin V(2) receptor

We have previously shown a conserved glutamate/dileucine motif ((335)ELRSLL(340)) in the intracellular C terminus of the vasopressin V(2) receptor (V(2) receptor) to be essential for receptor transport from the endoplasmic reticulum (ER) to the Golgi apparatus. The motif may represent a transport signal that is recognized by a component of ER to Golgi vesicles. Alternatively, it may be necessary for transport-competent receptor folding to pass the quality-control system of the ER. To assess these two possibilities, we constructed a receptor fragment that allows transport studies independent of full-length receptor folding. Transmembrane domains II-VII were deleted, thereby fusing the intracellular C terminus to the first cytoplasmic loop. The mutations that impaired transport of the full-length receptor were introduced, and receptor fragments were localized in transiently transfected HEK 293 cells. All mutant receptor fragments were detectable at the plasma membrane, demonstrating that the glutamate/dileucine motif does not function as a small, linear vesicular transport signal. Instead, our data strongly suggest that this motif is required for transport-competent folding of the full-length receptor. To assess the underlying conformational features, a three-dimensional homology model of the V(2) receptor was computed. Our model predicts that the glutamate/dileucine motif contributes to a U-like loop within the intracellular C terminus. Residue Leu(339) may be required for folding back the intracellular C terminus to residue Leu(62) of the first cytoplasmic loop. We characterized the naturally occurring L62P and DeltaL62-R64 mutations in the first cytoplasmic loop and show that they lead to transport-defective full-length V(2) receptors that are retained in the ER, consistent with the structure model.     

Epidemiology of diphyllobothriasis in the Valdivia river basin, Chile

In the Valdivia (Chile) river basin 1,295 inhabitants of 6 riverside districts were examined between March and October 1987 and showed a 1.2% of prevalence by Diphyllobothrium in the districts of Ri?ihue and Las Huellas. Prevalence of 5.3% and 9.8% respectively were registered in dogs of the districts of Ri?ihue and Malihue. No cat or pig infection was observed in the different districts. The parasites recovered after the treatment were identified as Diphyllobothrium latum. Human infection by D. latum in the districts affected results from the consumption of smoked or insufficiently cooked fish. The investigation of 1,450 fish (4 exotic species and 11 autochthonous ones), caught in the Valdivia river basin in 1986 and 1987, showed the existence of plerocercoids of D. latum and/or Diphyllobothrium dendriticum in Salmo gairdneri and Salmo trutta among exotic fish and in some autochthonous species. Prevalence and mean intensity in the infection of fish as well as the degree of aggregation in the infrapopulations varied in the different districts. Some species of fish would act as intermediary hosts and others as paratenic hosts in the life cycles of Diphyllobothrium spp. in the Valdivia river basin. An improvement in the conditions of basic sanitation, in sanitary education and in the treatment of infected persons is proposed as a means for the control of diphyllobothriasis in the districts affected.