Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones

PPAR gamma is required for fat cell development and is the molecular target of antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that inactivation of PPAR gamma in macrophages results in the development of significant glucose intolerance plus skeletal muscle and hepatic insulin resistance in lean mice fed a normal diet. This phenotype was associated with increased expression of inflammatory markers and impaired insulin signaling in adipose tissue, muscle, and liver. PPAR gamma-deficient macrophages secreted elevated levels of factors that impair insulin responsiveness in muscle cells in a manner that was enhanced by exposure to FFAs. Consistent with this, the relative degree of insulin resistance became more severe in mice lacking macrophage PPAR gamma following high-fat feeding, and these mice were only partially responsive to TZD treatment. These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs.     

The Arabidopsis homolog of trithorax, ATX1, binds phosphatidylinositol 5-phosphate, and the two regulate a common set of target genes

The Arabidopsis homolog of trithorax, ATX1, regulates numerous functions in Arabidopsis beyond the homeotic genes. Here, we identified genome-wide targets of ATX1 and showed that ATX1 is a receptor for a lipid messenger, phosphatidylinositol 5-phosphate, PI5P. PI5P negatively affects ATX1 activity, suggesting a regulatory pathway connecting lipid-signaling with nuclear functions. We propose a model to illustrate how plants may respond to stimuli (external or internal) that elevate cellular PI5P levels by altering expression of ATX1-controlled genes.     

Outcome and predictors of cardiopulmonary resuscitation among patients admitted in Medical Intensive Care Unit in North India

Background:

Outcome and predictors of survival after cardiopulmonary resuscitation (CPR) in Intensive Care Units (ICUs) have been extensively studied in western world, but data from developing countries is sparse.

Objectives:

To study the outcome and predictors of survival after CPR in a Medical ICU (MICU) of a tertiary level teaching hospital in North India.

Materials and Methods:

A 1-year prospective cohort study.

Results:

Of 105 in-MICU CPRs, forty patients (38.1%) achieved return of spontaneous circulation (ROSC). Only one patient (0.9%) survived up to hospital discharge. The predictors of ROSC were ventricular tachycardia/ventricular fibrillation as first monitored rhythm, intubation during CPR and CPR duration ≤ 10 min. CPR duration > 10 min was a significant factor for resuscitation failure.

Conclusions:

The rate of survival to hospital discharge after in-MICU CPRs is extremely poor. Our data may aid treating physicians, resuscitation teams, and families in understanding the likely outcome of patients after in-MICU CPRs.     

Determination of optimal cryoprotectants and procedures for their addition and removal from human spermatozoa

The objective was to test the hypothesis that the optimal cryoprotective agent for cryopreservation of human spermatozoa would be a solute for which cells have the highest plasma membrane permeability, resulting in the least amount of volume excursion during its addition and removal. To test this hypothesis, theoretical simulations were performed using membrane permeability coefficients to predict optimal procedures for the addition and removal of a cryoprotectant. Simulations were performed using data from four different cryoprotectants: (i) glycerol, (ii) dimethyl sulphoxide, (iii) propylene glycol and (iv) ethylene glycol. Thermodynamic formulations were applied to determine approaches for the addition and removal of 1 M and 2 M final concentrations of cryoprotectant, allowing the spermatozoa to maintain a cell volume within their osmotic tolerance limits. Based on these data, ethylene glycol was predicted to be optimal for minimizing volume excursions among the solutes evaluated. These predictions were then experimentally tested using glycerol as the control cryoprotectant and ethylene glycol as the experimental cryoprotectant. The results indicate that there was a higher (P < 0.05) recovery of motile spermatozoa after cryopreservation when using 1 M ethylene glycol than with 1 M glycerol, supporting the hypothesis that use of the cryoprotectant for which the cell has the highest permeability will result in higher cell survival.      

Donor insemination: Dutch parents' opinions about confidentiality and donor anonymity and the emotional adjustment of their children

Results from a comparative study investigating 38 donor insemination (DI) Dutch families with 4-8 year old children are presented. The aims of this study were to investigate parents' opinions on the issues of confidentiality and donor anonymity, to assess the emotional development of the children, and to examine in DI families the association between secrecy with regard to the use of a donor and the emotional adjustment of the children. The DI families were compared to families with a child conceived by in-vitro fertilization (IVF) and to families with a naturally conceived child. Secrecy appeared to be associated with DI and not with IVF: 74% of the DI parents intended not to inform the child about the way in which she/he was conceived, whereas none of the IVF parents intended to keep the secret. Only one set of DI parents and two sets of IVF parents had actually told the child. As to donor anonymity, a spread of opinions appeared among DI parents; 57% preferred an anonymous donor, 31% would have liked non- identifying information about the donor, 9% preferred the donor's identity to be registered and 3% remained unsure. Parents' major concern was to know more about the medical/genetic background of the donor. Mothers and fathers in the DI families differed in their opinions concerning the issues of confidentiality and donor anonymity: fathers, more often than mothers, were secretive with regard to the use of a donor and husbands, more often than their wives, were in favour of donor anonymity. With regard to the emotional development of the children, more emotional/behavioural problems were revealed among DI children than among children who were naturally conceived. No association was found between secrecy and the emotional/behavioural adjustment of the children.      

Effect of vitamin A adjunct therapy for cerebral malaria in children admitted to Mulago hospital: a randomized controlled trial

Background

Malaria is a leading cause of mortality in Uganda accounting for 25% of deaths among children. Hitherto no adjunct therapy has been identified to improve outcome of cerebral malaria. Retinol suppresses growth of P.falciparum, scavenges free radicals, and exhibits synergistic action with quinine in parasite clearance.

Objective

To determine the effect of vitamin A supplementation on treatment outcome of cerebral malaria

Methods

In this randomised double-blind placebo controlled clinical trial we studied 142 children aged 6–59 months admitted with cerebral malaria in Mulago Hospital, Kampala. Children were randomised to either vitamin A or placebo and followed for 7 days. The main outcome measures were coma recovery time, time for convulsions to stop, and parasite and fever clearance. Secondary outcomes were overall mortality and time taken to start oral feeds.

Results

There was no difference in the coma recovery time (p=0.44), resolution of convulsions (p=0.37), fever clearance (p=0.92), parasite clearance (p=0.12), and starting oral feeds between the two treatment groups. Mortality was higher (16.2%) in the placebo than in the vitamin A group (8.1%): RR 1.4; 95% CI 1.0–2.1.

Conclusions

Vitamin A as adjunct therapy did not significantly reduce coma duration but there were fewer deaths in the vitamin A arm.