Peter Winter

Mechanisms of Cerebrovascular O2 Sensitivity from Hyperoxia to Moderate Hypoxia in the Rat

Cerebrovascular dilation over PaO2 ranging from hyperoxia to moderate hypoxia is unexplained. We hypothesize that tissue acidosis is the cause. Local cortical cerebral blood flow (LCBF), tissue hydrogen ion concentration [H+]t, and tissue Po2 (Pto2) were measured with microelectrodes in the parietal cortex of 18 rats during a 30-min steady state on 60 to 10% inspired O2 (Pao2, 300 to 40 torr) during 40% N2O analgesia. Five rats kept on 60% O2/40% N2O served as controls. In 18 rats at a Pao2 of 275 ± 7 torr (X̄ ± SEM) and Paco2 of 35 ±1 torr, cerebral values were: LCBF = 129 ± 23 (X̄ ± SEM) ml · 100 g−1 · min−1; [H+], = 62 ± 6 nM; and Pto2 = 25 ± 3 torr. As Pao2 was reduced from about 300 to 40 torr, changes in these variables in percentage of control with respect to Pao2, were described by the following equations, all at P < 0.0001: LCBF = 85.9 + 5,572/Pao2; [H+]t = 97.15 + 1,012/Pao2; and = 108.8 − 3,492/Pao2. Simultaneous solution of the LCBF and [H+]t equations at various Pao2 revealed a slope of 8.82%/nM. Direct correlation between LCBF in ml · 100 g−1 · min−1 and [H+]t in nM revealed a linear relationship defined by the equation Y = − 7.472 + 1.6705X (r = 0.6426) for [H+]t between 56 and 160 nM (pH = 7.25 and 6.80) but no correlation at [H+]t values between 56 and 32 nM (pH = 7.25 to 7.50). Cerebrovascular tone is directly correlated with [H+]t during progressive, 30-min steady-state reduction in Pao2 from 350 to 40 torr.

Anesthetics modulate phospholipase C hydrolysis of monolayer phospholipids by surface pressure.

Anesthetics are believed to produce anesthesia through the reversible inhibition of synaptic transmission but how this is accomplished is unknown. Based on earlier studies of anesthetic-enzyme-phospholipid interaction, we surmised that anesthetics may inhibit synaptic transmission by increasing synaptic membrane lateral pressure thereby inhibiting phospholipid hydrolysis, membrane transduction and synaptic transmission. As a first approximation towards investigating this concept, we hypothesized that anesthetics modulate the rate of phospholipase C hydrolysis of a lipid monolayer through its effects on surface pressure. The relationship between the hydrolysis rate of a monolayer of dipalmitoylphosphatidylcholine [14C-choline] (DPPC) by phospholipase C (Plase C) and monolayer surface pressure (SP) as altered by either halothane, isoflurane, or by physical compression at 37 degrees C was studied. The decline in surface 14C-activity as the [14C]choline diffuses into the Krebs-Ringer bicarbonate buffer aqueous subphase is estimated as the rate of DPPC hydrolysis measured by the initial slope method. DPPC hydrolysis was about 300 cpm/min and constant between SP of 0 to 20 dynes/cm. Higher SP between 25 and 30 dyne/cm, whether induced by halothane, isoflurane or physical compression, increased the rate of hydrolysis by 5-fold to a peak rate of about 1600 cpm/min at 25-30 dynes/cm. At a SP above 32 dynes/cm, DPPC hydrolysis abruptly ceased. We conclude that anesthetics can reversibly inhibit synaptic transmission through their effects on synaptic membrane lateral pressure. We also speculate that membrane lateral pressure may be a highly sensitive means of controlling membrane function through alteration in membrane lipid composition, membrane enzyme activity, receptor affinity and ion channel permeability.

Cerebral Cortical Oxygenation and Perfusion during Progressive Normovolaemic Haemodilution with Hetastarch (Volex) and Fluosol-DA

In a previous study on the effects of normovolaemic haemodilution with Hetastarch on cerebral cortical oxygenation and perfusion, we found that cortical tissue PO2 (PtO2) was unchanged between haematocrits (Hct) of 45 to 38%, but then fell at a rate of about 2.4% per 1% decrease in Hct between Hct of 38% to 5% (Shinozuka, Nemoto and Bleyaert, 1984). Fluosol-DA may delay the fall in cerebral cortical PtO2 during normovolaemic haemodilution compared with haemodilution with Hetastarch.

Detrimental cerebrometabolic effects of hyperoxia in newborn rats

To investigate the pathogenesis of oxygen toxicity in the newborn brain, we exposed one-day-old Sprague-Dawley albino rats to 100% O(2) and measured whole-brain high-energy phosphates, glucose, lactate, and free fatty acids (FFA) after 0, 15, 30, 60 and 120 min. Whole-brain adenosine triphosphate and creatine phosphate fell significantly from about 4.5 to 2.5 ?mol-mg(?1) protein. Brain lactate remained at about 0.3 ?mol.mg(?1) protein in hyperoxic rats, but increased in normoxic rats, from 0.3 to 1.3 ?mol.mg(?1) protein at 120 min. Total FFA decreased from 30 to 15 nmol.mg(?1) protein during normoxia, but increased to 40 nmol.mg(?1) protein during hyperoxia. Undetectable in normoxic rats, arachidonic acid increased to between 4 and 6 nmol.mg(?1) protein during hyperoxia while oleic acid increased by two to threefold. In normoxia, palmitate decreased by 70% from 12 to 4 nmol.mg(?1) protein whereas in hyperoxia it remained at 10 nmol.mg(?1) protein. Normobaric 100% O(2) has detrimental metabolic effects on the neonatal brain which cannot be attributed to cerebral vasospasm or seizure-induced cerebral anoxia because lactic acidosis was not observed. FFA changes suggest that a likely explanation is membrane lipid peroxidation from O(2)-induced free radicals.

Data on draft genome sequence of chickpea (Cicer arietinum)

The dataset contains genome sequence of the ~738 Mb chickpea genome from CDC Frontier, a kabuli variety, which contains an estimated 28,269 genes. Re-sequencing and analysis of 90 cultivated and wild genotypes from 10 different countries identifies both targets of breeding-associated genetic sweeps and targets of breeding-associated balancing selection. Candidate genes for disease resistance and agronomic traits are highlighted, including traits that distinguish the two main classes of cultivated chickpea- desi and kabuli. These data comprise a resource for chickpea improvement through molecular breeding, and provide insights into both genome diversity and domestication. GBrowse Visualization Links: Chickpea genome at LIS Research Article

Genetic map of ICC 4958 (C. arietinum) × PI 489777 (C. reticulatum) with 1291 markers

This dataset contains genetic map data developed based on recombinant inbred line (RIL) population ICC 4958 (C. arietinum) x PI 489777 (C. reticulatum). This map consists of 1,291 markers on eight linkage groups (LGs) spanning a total of 845.56 cM. The number of markers per linkage group ranged from 68 (LG 8) to 218 (LG 3) with an average inter-marker distance of 0.65 cM. While the developed resource of molecular markers will be useful for genetic diversity, genetic mapping and molecular breeding applications, the comprehensive genetic map with integrated BES-SSR markers will facilitate its anchoring to the physical map (under construction) to accelerate map-based cloning of genes in chickpea and comparative genome evolution studies in legumes. CMap Visualization Links: ICC4958 x PI 489777 DOI: doi:10.1371/journal.pone.0027275

Inter-specific genetic map of C. arietinum ICC 4958 × C. reticulatum PI 489777

311 SSRs and 71 gene based SNPs were developed from mapping population of C. arietinum ICC 4958 × C. reticulatum PI 489777 CMap Visualization Links: ICC 4958 X PI 489777 DOI: doi:10.1007/s00122-010-1265-1

A Method to increase recovery of fentanyl from urine

Fentanyl, a highly lipophilic drug (pk(a) 7.7), is a common drug of abuse. The current standard techniques to detect fentanyl in urine have low recovery rates and poor sensitivity. We report a modified solvent extraction technique that can recover between 63 and 86% of the drug with a detection limit of 0.2 ng/10 ml of urine. In addition, we report the duration of urinary fentanyl excretion in 11 adolescent patients administered either low (less than 10 mg/kg) or high (20-40 mg/kg) doses of fentanyl as part of anesthesia. The mean duration of urinary fentanyl excretion was similar in the two groups, with duration ranging from 1 to 5 days, and urine fentanyl concentration ranging from 0.1 ng to 10.3 ng/10 ml of urine.

Active and Basal Cerebrometabolic Rate for Oxygen (CMRO2) After Complete Global Brain Ischemia in Rats

The ultimate goal of this study is to devise a method for prognostic assessment of the viability of the brain in prolonged coma or in the vegetative state. The method we are attempting to develop is based upon the following hypotheses and observations: (1) The capacity of the brain to support spontaneous electrical activity (i.e., synaptic transmission) is the essence of viability; (2) severe neurologic dysfunction occurs not only as a result of irreversible neuronal necrosis but also, a potentially reversible failure of synaptic transmission in viable neurons (i.e., quiescent neurons); (3) active CMRO2 (ACMRO2) is O2 consumed to generate energy to support spontaneous brain electrical activity (i.e., restoration of neuronal ionic gradients after depolariztion) while basal CMRO2 (BCMRO2) provides the energy needed to maintain ionic gradients and energy-requiring anabolic reactions to maintain the viability of the neuron in the resting state;1,2 and (4) barbiturates, namely, thiopental, blocks spontaneous brain electrical activity and therefore, ACMRO2, while BCMRO2 is unaffected.3 Thus, the compartmentation of total CMRO2 into ACMRO2 and BCMRO2 after cerebral insults will allow estimates on the viability of the brain (ACMRO2) and neuronal necrosis (BCMRO2).