Proton selective substate of the mitochondrial permeability transition pore: regulation by the redox state of the electron transport chain

The permeability transition pore of rat liver mitochondria can be closed by chelating free Ca2+, with respect to the passage of large molecules such as mannitol and sucrose. However, an apparent H+-conducting substate remains open under these conditions, as indicated by the persistence of maximal O2 consumption rates and by the failure to recover a membrane potential. Agents which favor a closed pore, such as cyclosporin A, ADP, Mg2+, or bovine serum albumin, do not close the H+-conducting substate, but it closes spontaneously when respiration becomes limited by the availability of O2. Closure provoked by an O2 limitation requires free Mg2+ in the sub-micromolar concentration range and becomes less efficient with increasing time spent in the presence of free Ca2+. The H+-conducting substate is apparently regulated by the redox status of the electron transport chain, with a reduced form favoring closure. A physical association (or equivalence) between the pore and one of the respiratory chain complexes is supported. These characteristics suggest that the transition is irreversible in vivo, if it involves a small fraction of total mitochondria, and would lead to their elimination and/or replacement by the cell. The implications of this proposal are considered, as they relate to a possible role for the transition in cellular apoptosis and the elimination of mitochondria containing mutated DNA.     

Effect of novel mixed ETA/ETB antagonists on responses to ET-1 in human small muscular pulmonary arteries

Selective ETA and ETB receptor antagonists do not fully inhibit responses to ET-1 in human small pulmonary arteries. Here, we have compared the influence of the novel mixed ETA/ETB antagonists SB/217242, SB/234551 and SB/209670 on ET-1-mediated vasoconstriction in these vessels. ET-1 was a potent vasoconstrictor (pEC50: 8.14+/-0.05, n=5) and the concentration-response curve to ET-1 was biphasic in nature. All three mixed antagonists (1 microM) inhibited the responses to ET-1, abolishing the biphasic form of the concentration response curve. The order of potency was SB 209670>SB 234551>/=SB 217242 with estimated pKb values of 8.0+/-0.20, 6.8+/-0.17 and 6. 6+/-0.11 respectively (n=3-5).     

The use of pupillometry for the timely diagnosis of the intoxication by cholinesterase inhibitors

The article deals with diagnostic potential of new generation pupillometers having hi-tech units and using up-to-date methods of information processing. Those pupillometers proved to be effective for express diagnosis of intoxications.     

Socioeconomic and demographic factors are associated with worldwide patterns of stunting and wasting of children

We estimated the variability among nations in the prevalence of stunting and wasting, evaluated which national factors are associated with stunting and wasting and examined the relationship of stunting with wasting. The World Health Organization Global Database on Child Growth, a comprehensive conceptual model and a database of national factors were used with variance components and regression analyses. There was substantial variability among nations and among provinces within nations. Most national variability for stunting (76%) and wasting (66%) was explained by national factors and geographic region. Higher energy availability, female literacy and gross product were the most important factors associated with lower prevalence of stunting. The association of health expenditures and stunting differed by region. Higher immunization rate and, for Asia only, energy availability were the most important factors associated with lower prevalence of wasting. Regional differences in the relationship between stunting and wasting were accounted for by national factors. Some factors associated with stunting and wasting differ at the national level. Child malnutrition within a household is greatly influenced by issues at national and provincial levels, and intervention should be considered at all three levels.     

Wafer-scale optimization using computational availability

It is shown that, given the ability to restructure wafer-level designs, there are different ways to employ redundancy. Redundancy is evaluated by estimating system computational availability over a mission lifetime. This technique is illustrated using two wafer-scale integration (WSI) case studies. The first is a very-fine-grained programmable systolic data processor (PSDP) that contains 4- and 8-b paths, RAM, and control optimized for signal and data processing applications. The second, the Mosaic multicomputer architecture, is a less fine-grained homogeneous architecture in which each node contains a 16-b microprocessor and associated RAM and ROM. Potential benefits of implementing these parallel processing architectures in wafer scale are discussed     

Contributions of the left and right cerebral hemispheres to line bisection

Thirty-one right-hemisphere lesioned (RHL) patients, 11 left-hemisphere lesioned patients (LHL) and 10 normal controls (NC) bisected lines in three spatial location and four directional cuing conditions. The error direction and error size were analyzed as separate and combined variables. Seventy-seven percent of RHL patients and 45% of LHL patients made abnormally large errors in line bisection. Right-hemisphere lesioned patients were more sensitive to spatial location and directional cuing than NC subjects. In contrast, LHL patients were less sensitive to either condition than NCs. The error direction and error size emerged as dissociable components of line bisection. Right-hemisphere lesioned patients and NC subjects bisected lines consistently to one side of the true center. Left-hemisphere lesioned patients bisected lines equally often on both sides of the true center. Both RHL and LHL patients made larger absolute bisection errors than NC subjects, but the RHL patient's errors were larger than those of the LHL patients. We propose that the greater sensitivity of RHL patients to spatial location and directional cues and the directional consistency of their bisection errors represent contributions of the intact left cerebral hemisphere to line bisection. In contrast, the LHL patient's unrestrained ability to orient to both ends of the line reflects a contribution of the intact right cerebral hemisphere to line bisection. The failure of both groups to accurately bisect lines reflects a common visuospatial processing deficit that is more pronounced following RHLs than LHLs.