Brain-Derived Neurotrophic Factor in Post-Partum Depressive Mothers

Postpartum depression (PPD) is the most common psychiatric complication observed in women after they give birth. Some women are particularly sensitive to hormonal changes, starting in early menarche, thus increasing their vulnerability to psychological stressing agents that are triggered by environmental and physiological factors throughout their lives. Decreased serum brain-derived neurotrophic factor (BDNF) levels have been associated to different neuropsychiatric conditions and BDNF has been considered as a candidate marker for such dysfunctions. The goal of this study was to compare the levels of BDNF between mothers who suffer from PPD and healthy control mothers as well as to searching for associations between BDNF levels and the severity of PPD. This is a case-control study including 36 mothers with PPD and 36 healthy control mothers. PPD was defined according to the Beck Depression Inventory (BDI). Serum BDNF was assayed with the sandwich ELISA method. Results: Serum levels of BDNF were significantly lower in women with PPD than in control mothers (P?≤?0.03). A significant negative correlation between BDI score and serum BDNF levels was observed (P?≤?0.02 and r?=?-0.29). Our study demonstrated that low BDNF levels are associated with PPD. This result point out to the potential usage of BDNF in the screening of PPD, which could promote early treatment and, therefore, reduce the burden to the PPD women and to the health system.     

A longitudinal study of the association between dietary factors, serum lipids, and bone marrow lesions of the knee

Introduction  

Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs.     

Feasibility of Distributing Rapid Diagnostic Tests for Malaria in the Retail Sector: Evidence from an Implementation Study in Uganda

Background

Despite the benefits of malaria diagnosis, most presumed malaria episodes are never tested. A primary reason is the absence of diagnostic tests in retail establishments, where many patients seek care. Malaria rapid diagnostic tests (RDTs) in drug shops hold promise for guiding appropriate treatment. However, retail providers generally lack awareness of RDTs and training to administer them. Further, unsubsidized RDTs may be unaffordable to patients and unattractive to retailers. This paper reports results from an intervention study testing the feasibility of RDT distribution in Ugandan drug shops.

Methods and Findings

92 drug shops in 58 villages were offered subsidized RDTs for sale after completing training. Data on RDT purchases, storage, administration and disposal were collected, and samples were sent for quality testing. Household surveys were conducted to capture treatment outcomes. Estimated daily RDT sales varied substantially across shops, from zero to 8.46 RDTs per days. Overall compliance with storage, treatment and disposal guidelines was excellent. All RDTs (100%) collected from shops passed quality testing. The median price charged for RDTs was 1000USH ($0.40), corresponding to a 100% markup, and the same price as blood slides in local health clinics. RDTs affected treatment decisions. RDT-positive patients were 23 percentage points more likely to buy Artemisinin Combination Therapies (ACTs) (p = .005) and 33.1 percentage points more likely to buy other antimalarials (p<.001) than RDT-negative patients, and were 5.6 percentage points more likely to buy ACTs (p = .05) and 31.4 percentage points more likely to buy other antimalarials (p<.001) than those not tested at all.

Conclusions

Despite some heterogeneity, shops demonstrated a desire to stock RDTs and use them to guide treatment recommendations. Most shops stored, administered and disposed of RDTs properly and charged mark-ups similar to those charged on common medicines. Results from this study suggest that distributing RDTs through the retail sector is feasible and can reduce inappropriate treatment for suspected malaria.     

PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia

Phosphorylation of the activation domain of protein kinase C (PKC) isoforms is essential to start a conformational change that results in an active catalytic domain. This activation is necessary not only for newly synthesized molecules, but also for kinase molecules that become dephosphorylated and need to be refolded and rephosphorylated. This "rescue" mechanism is responsible for the maintenance of the steady-state levels of atypical PKC (aPKC [PKCι/λ and ζ]) and is blocked in inflammation. Although there is consensus that phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized molecules, it is unclear what kinase performs that function during the rescue and where the rescue takes place. To identify the activating kinase during the rescue mechanism, we inhibited protein synthesis and analyzed the stability of the remaining aPKC pool. PDK1 knockdown and two different PDK1 inhibitors-BX-912 and a specific pseudosubstrate peptide-destabilized PKCι. PDK1 coimmunoprecipitated with PKCι in cells without protein synthesis, confirming that the interaction is direct. In addition, we showed that PDK1 aids the rescue of aPKC in in vitro rephosphorylation assays using immunodepletion and rescue with recombinant protein. Surprisingly, we found that in Caco-2 epithelial cells and intestinal crypt enterocytes PDK1 distributes to an apical membrane compartment comprising plasma membrane and apical endosomes, which, in turn, are in close contact with intermediate filaments. PDK1 comigrated with the Rab11 compartment and, to some extent, with the transferrin compartment in sucrose gradients. PDK1, pT555-aPKC, and pAkt were dependent on dynamin activity. These results highlight a novel signaling function of apical endosomes in polarized cells.     

Reconstitution of the complement channel into lipid vesicles and planar bilayers starting from the fluid phase complex

Proteolysis of the fluid phase complement complex SC5b-9 transforms it into an arnphiphilic molecule which resembles the membrane attack complex of complement and reconstitutes into lipid vesicles. Complement-containing vesicles prepared in this way can be made to fuse with planar lipid bilayers transferring their protein content to the host membrane. Massive conductance increases can thus be observed, which are due to the insertion of a large number of ionic channels into the membrane. Using low concentrations of vesicles, single channels can be studied.     

Biofilm development and cell death in the marine bacterium Pseudoalteromonas tunicata

The newly described green-pigmented bacterium Pseudoalteromonas tunicata (D2) produces target-specific inhibitory compounds against bacteria, algae, fungi, and invertebrate larvae and is frequently found in association with living surfaces in the marine environment. As part of our studies on the ecology of P. tunicata and its interaction with marine surfaces, we examined the ability of P. tunicata to form biofilms under continuous culture conditions within the laboratory. P. tunicata biofilms exhibited a characteristic architecture consisting of differentiated microcolonies surrounded by water channels. Remarkably, we observed a repeatable pattern of cell death during biofilm development of P. tunicata, similar to that recently reported for biofilms of Pseudomonas aeruginosa (J. S. Webb et al., J. Bacteriol. 185:4585-4595, 2003). Killing and lysis occurred inside microcolonies, apparently resulting in the formation of voids within these structures. A subpopulation of viable cells was always observed within the regions of killing in the biofilm. Moreover, extensive killing in mature biofilms appeared to result in detachment of the biofilm from the substratum. A novel 190-kDa autotoxic protein produced by P. tunicata, designated AlpP, was found to be involved in this biofilm killing and detachment. A Delta alpP mutant derivative of P. tunicata was generated, and this mutant did not show cell death during biofilm development. We propose that AlpP-mediated cell death plays an important role in the multicellular biofilm development of P. tunicata and subsequent dispersal of surviving cells within the marine environment.     

The Impact of Exogenic Testosterone and Nortestosterone-Decanoate Toxicological Evaluation Using a Rat Model

The impact of exogenic testosterone (T): 1.5 and 3.0 mg/kg.bw) and 19-nortestosterone 17-decanoate (ND): 1.5 and 7.5 mg/kg.bw) in castrated male rats was evaluated based on: (a) weight increase of the androgen target tissues, respecting the Hershberger methodology; (b) the 17α and β-testosterone, 17 α and β-estradiol and 17 α and β-nortestosterone levels using the GC-MS/MS technique; and (c) observation of the serum free thyroxine levels (T₄). Results revealed that T and ND significantly increased the weight of androgen target tissues as follows: ND was more influential on seminal vesicles, levator ani-bulbocavernosus muscle (LABC) and Cowper''s glands and T (at a dose of 3.0 mg/kg.bw) influenced the weight of the ventral prostate and glans penis. Serum samples analyzed for steroid hormone levels showed the presence of 17β-testosterone, 17β-estradiol and 17β-nor-testosterone, in castrated male rats injected with testosterone and nortestosterone, but no significant differences were found between thyroid responses and thyroid hormone levels. The results of this research proved the disrupting activity of T and ND when administered in high doses and the useful application of the Hershberger bioassay in the case of ND.     

Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver

The exposure to an increased supply of nutrients before birth may contribute to offspring obesity. Offspring from obese dams that chronically consume a high-fat diet present clinical features of metabolic syndrome, liver lipid accumulation and activation of c-Jun N-terminal kinases (JNK) consistent with the development of nonalcoholic fatty liver disease (NAFLD). However, in spite of the importance of the resistance to insulin for the development of NAFLD, the molecular alterations in the liver of adult offspring of obese dams are yet to be investigated. In this study, we tested the hypothesis that the consumption of excessive saturated fats during pregnancy and lactation contributes to adult hepatic metabolic dysfunction in offspring. Adult male offspring of dams fed a high-fat diet (HN) during pregnancy and lactation exhibited increased fat depot weight; increased serum insulin, tumor necrosis factor α and interleukin 1β; and reduced serum triglycerides. Liver showed increased JNK and I kappa B kinase phosphorylation and PEPCK expression in the adult. In addition, liver triglyceride content in the offspring 1 week after weaning and in the adult was increased. Moreover, basal ACC phosphorylation and insulin signaling were reduced in the liver from the HN group as compared to offspring of dams fed a standard laboratory chow (NN). Hormone-sensitive lipase phosphorylation (Ser565) was reduced in epididymal adipose tissue from the HN group as compared to the NN group. It is interesting that all changes observed were independent of postweaning diet in 14-week-old offspring. Therefore, these data further reinforce the importance of maternal nutrition to adult offspring health.