Myocardial effects of halothane and isoflurane in senescent rats

BACKGROUND: Aging is associated with marked alterations in myocardial contraction and relaxation, whereas halogenated anesthetics depress myocardial contractility. However, their effects on aging myocardium are unknown. METHODS: Mechanical variables of left ventricular papillary muscles from adult and senescent rats (29 degrees C; pH 7.40; Ca2+ 1.0 or 0.5 mM; stimulation frequency, 12 pulses/min) were studied. The expression of genes coding for the alpha and beta-myosin heavy chain (MHC) and Ca2+ -ATPase of the sarcoplasmic reticulum (SR) were studied. The effects of halothane and isoflurane were studied. The inotropic effects were compared under low and high loads, using the maximum unloaded shortening velocity (Vmax) and maximum isometric active force (AF). The lusitropic effects were compared in isotonic and isometric conditions. RESULTS: Senescent rats had a decrease in contraction and relaxation velocities, associated with a reexpression of beta-MHC mRNAs and a decrease in SR Ca2+ -ATPase mRNAs. Halothane induced a lower negative inotropic effect in senescent rats (1.5 vol%, AF: 53 +/- 14% vs. 39 +/- 12% of baseline values; P < 0.01) whereas isoflurane induced a similar negative inotropic effect (1.5 vol%, AF: 81 +/- 7% vs. 87 +/- 7% of baseline values; NS). Halothane induced a negative lusitropic effect in isotonic conditions in adult, but not in senescent, rats. CONCLUSIONS: The inotropic and lusitropic effects of halothane were less important in senescent than in adult rats, whereas the effects of isoflurane were similar. These differences are probably related to differences in SR function and in the effects of halogenated anesthetics on the SR.     

The role of sexually transmitted infections in male circumcision effectiveness against HIV – insights from clinical trial simulation

Background  

A landmark randomised trial of male circumcision (MC) in Orange Farm, South Africa recently showed a large and significant reduction in risk of HIV infection, reporting MC effectiveness of 61% (95% CI: 34%–77%). Additionally, two further randomised trials of MC in Kisumu, Kenya and Rakai, Uganda were recently stopped early to report 53% and 48% effectiveness, respectively. Since MC may protect against both HIV and certain sexually transmitted infections (STI), which are themselves cofactors of HIV infection, an important question is the extent to which this estimated effectiveness against HIV is mediated by the protective effect of circumcision against STI. The answer lies in the trial data if the appropriate statistical analyses can be identified to estimate the separate efficacies against HIV and STI, which combine to determine overall effectiveness.     

Illness-related behaviour and utilization of oral health services among adult city-dwellers in Burkina Faso: evidence from a household survey

Background  

In sub-Saharan Africa, the availability and accessibility of oral health services are seriously constrained and the provision of essential oral care is limited. Reports from the region show a very low utilization of oral health care services, and visits to dental-care facilities are mostly undertaken for symptomatic reasons. The objectives of the present study were to describe the prevalence of oral symptoms among adults in Ouagadougou, capital city of Burkina Faso and the use of oral health services and self-medication in response to these symptoms and to measure the associations between predisposing, enabling and needs factors and decisions to seek oral health care.     

Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients

OBJECTIVE: To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression. RESULTS: A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks. CONCLUSION: Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.     

Calculation of absolute protein-ligand binding free energy from computer simulations

A general methodology for calculating the equilibrium binding constant of a flexible ligand to a protein receptor is formulated on the basis of potentials of mean force. The overall process is decomposed into several stages that can be computed separately: the free ligand in the bulk is first restrained into the conformation it adopts in the bound state, position, and orientation by applying biasing potentials, then it is translated into the binding site, where it is released completely. The conformational restraining potential is based on the root-mean-square deviation of the peptide coordinates relative to its average conformation in the bound complex. Free energy contributions from each stage are calculated by means of free energy perturbation potential of mean force techniques by using appropriate order parameters. The present approach avoids the need to decouple the ligand from its surrounding (bulk solvent and receptor protein) as is traditionally performed in the double-decoupling scheme. It is believed that the present formulation will be particularly useful when the solvation free energy of the ligand is very large. As an application, the equilibrium binding constant of the phosphotyrosine peptide pYEEI to the Src homology 2 domain of human Lck has been calculated. The results are in good agreement with experimental values.