Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-child-transmission of HIV in Tanzania.

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health

Factors associated with dental caries among institutionalized residents with schizophrenia in Taiwan: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Little research has been done on the relationship between dental caries and the personal characteristics of institutionalized residents diagnosed with schizophrenia. This study investigates the individual and treatment factors associated with the dental caries among institutionalized residents with schizophrenia in Taiwan.</p> <p>Methods</p> <p>An oral health survey of institutionalized residents with schizophrenia in the largest public psychiatric hospital was conducted in Taiwan in 2006. Based on this data, multiple logistic analyses were used to determine the relationship between some explanatory variables and the outcome variables of dental caries among subjects with schizophrenia.</p> <p>Results</p> <p>Among the 1,108 subjects with schizophrenia, age was the only variable independently associated with DMFT > 8 (OR = 7.74, 95% CI = 3.86-15.55, p < 0.001 in comparison to residents aged 65 + years vs. 20-44 years; OR = 3.06, 95% CI = 2.03-4.61, p < 0.001 in comparison to residents aged 55-64 years vs. 20-44 years) after making adjustments for other explanatory variables. In addition, those with an education of only elementary school (OR = 1.67, 95% CI = 1.08-2.56, p = 0.021), low income (OR = 1.58, 95% CI = 1.02-2.44, p = 0.039), and length of stay (LOS) of > 10 years (OR = 2.09, 95% CI = 1.30-3.37, p = 0.002) were associated with a care index < 54.7%. Older age, lower educational level, and longer hospital stays were associated with number of remaining teeth being < 24.</p> <p>Conclusions</p> <p>Aging was the most important factor related to a high level of dental caries. Low educational level, low income, and LOS were also associated with the indicators of dental caries among institutionalized subjects with schizophrenia. It is necessary to address the treatment factors such as prolonged stay in institutions when decision-makers are planning for preventive strategies of oral health for institutionalized residents with schizophrenia.</p

Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions

The aim of the present study was to determine whether treatment with liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, would alter mammalian target of rapamycin complex 1 (mTORC1) signaling and/or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor activity under dexamethasone-induced toxic conditions. Western blot analyses were performed to assess changes in mTORC1-mediated proteins, brain-derived neurotrophic factor (BDNF), and various synaptic proteins (PSD-95, synapsin I, and GluA1) in rat hippocampal cultures under toxic conditions induced by dexamethasone, which causes hippocampal cell death. Hippocampal dendritic outgrowth and spine formation were measured using immunostaining procedures. Dexamethasone significantly decreased the phosphorylation levels of mTORC1 as well as its downstream proteins. However, treatment with liraglutide prevented these reductions and significantly increased BDNF expression. The increase in BDNF expression was completely blocked by rapamycin and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). Liraglutide also recovered dexamethasone-induced decreases in the total length of hippocampal dendrites and reductions in spine density in a concentration-dependent manner. However, the positive effects of liraglutide on neural plasticity were abolished by the blockade of mTORC1 signaling and AMPA receptors. Furthermore, liraglutide significantly increased the expression levels of PSD-95, synapsin I, and GluA1, whereas rapamycin and NBQX blocked these effects. The present study demonstrated that liraglutide activated mTORC1 signaling and AMPA receptor activity as well as increased dendritic outgrowth, spine density, and synaptic proteins under toxic conditions in rat primary hippocampal neurons. These findings suggest that GLP-1 receptor (GLP-1R) activation by liraglutide may affect neuroplasticity through mTORC1 and AMPA receptors

Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: A meta-analysis

Background: We present a systematic review and meta-analysis of the available clinical trials concerning the usefulness of aripiprazole in the treatment of the psychotic symptoms in bipolar disorder.Methods: A systematic MEDLINE and repository search concerning clinical trials for aripiprazole in bipolar disorder was conducted.Results: The meta-analysis of four randomised controlled trials (RCTs) on acute mania suggests that the effect size of aripiprazole versus placebo was equal to 0.14 but a more reliable and accurate estimation is 0.18 for the total Positive and Negative Syndrome Scale (PANSS) score. The effect was higher for the PANSS-positive subscale (0.28), PANSS-hostility subscale (0.24) and PANSS-cognitive subscale (0.20), and lower for the PANSS-negative subscale (0.12). No data on the depressive phase of bipolar illness exist, while there are some data in favour of aripiprazole concerning the maintenance phase, where at week 26 all except the total PANSS score showed a significant superiority of aripiprazole over placebo (d = 0.28 for positive, d = 0.38 for the cognitive and d = 0.71 for the hostility subscales) and at week 100 the results were similar (d = 0.42, 0.63 and 0.48, respectively).Conclusion: The data analysed for the current study support the usefulness of aripiprazole against psychotic symptoms during the acute manic and maintenance phases of bipolar illness. © 2009 Fountoulakis et al; licensee BioMed Central Ltd

The 4q12 Amplicon in Malignant Peripheral Nerve Sheath Tumors: Consequences on Gene Expression and Implications for Sunitinib Treatment

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive tumors which originate from Schwann cells and develop in about 10% of neurofibromatosis type 1 (NF1) patients. The five year survival rate is poor and more effective therapies are needed. Sunitinib is a drug targeting receptor tyrosine kinases (RTK) like PDGFRα, c-Kit and VEGFR-2. These genes are structurally related and cluster on chromosomal segment 4q12.) was present in MPNST cell lines suggesting an autocrine loop. We show that VEGF triggered signal transduction via the MAPK pathway, which could be blocked by sunitinib. might serve as predictive markers for efficacy of sunitinib

Back to Basics: Pitting Edema and the Optimization of Hypertension Treatment in Incident Peritoneal Dialysis Patients (BRAZPD)

Systemic arterial hypertension is an important risk factor for cardiovascular disease that is frequently observed in populations with declining renal function. Initiation of renal replacement therapy at least partially decreases signs of fluid overload; however, high blood pressure levels persist in the majority of patients after dialysis initiation. Hypervolemia due to water retention predisposes peritoneal dialysis (PD) patients to hypertension and can clinically manifest in several forms, including peripheral edema. The approaches to detect edema, which include methods such as bioimpedance, inferior vena cava diameter and biomarkers, are not always available to physicians worldwide. For clinical examinations, the presence of pitting located in the lower extremities and/or over the sacrum to diagnose the presence of peripheral edema in their patients are frequently utulized. We evaluated the impact of edema on the control of blood pressure of incident PD patients during the first year of dialysis treatment. Patients were recruited from 114 Brazilian dialysis centers that were participating in the BRAZPD study for a total of 1089 incident patients. Peripheral edema was diagnosed by the presence of pitting after finger pressure was applied to the edematous area. Patients were divided into 2 groups: those with and without edema according to the monthly medical evaluation. Blood arterial pressure, body mass index, the number of antihypertensive drugs and comorbidities were analyzed. We observed an initial BP reduction in the first five months and a stabilization of blood pressure levels from five to twelve months. The edematous group exhibited higher blood pressure levels than the group without edema during the follow-up. The results strongly indicate that the presence of a simple and easily detectable clinical sign of peripheral edema is a very relevant tool that could be used to re-evaluate not only the patient's clinical hypertensive status but also the PD prescription and patient compliance