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Biomedical subjects

E Edwards

Publications and source records attributed to E Edwards.

At least 19 recordsLinked to original sources

High gamma power is phase-locked to theta oscillations in human neocortex.

We observed robust coupling between the high- and low-frequency bands of ongoing electrical activity in the human brain. In particular, the phase of the low-frequency theta (4 to 8 hertz) rhythm modulates power in the high gamma (80 to 150 hertz) band of the electrocorticogram, with stronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.

Adult↗

New Zealand national incidence of bronchiectasis "too high" for a developed country.

AIMS: To prospectively estimate the incidence of bronchiectasis among New Zealand (NZ) children, to consider aetiology and severity, and to evaluate regional and ethnic variation. METHODOLOGY: NZ paediatricians were surveyed monthly for new cases of bronchiectasis during 2001 and 2002 via the NZ paediatric surveillance unit (with coverage of >94% of NZ paediatricians). Notified cases had their computed tomography scans reviewed and scored for severity. Confirmed cases were followed up by postal questionnaire one year after diagnosis. Demographic, aetiological, and severity data were collected. RESULTS: Ninety nine notifications were received. Sixty five cases were confirmed. An overall incidence of 3.7 per 100,000 under 15 year old children per year was estimated. Incidence was highest in Pacific children at 17.8 compared with 4.8 in Maori, 1.5 in NZ European, and 2.4 other per 100,000 per year. Incidence varied significantly by region. The median age at diagnosis was 5.2 years; the majority had symptoms for more than two years. Eighty three per cent had bilateral disease, with a median of three lobes affected, mean FEV1 of 77% predicted, and modified Bhalla HRCT score of 18. CONCLUSIONS: The incidence of bronchiectasis is high in NZ children, nearly twice the rate for cystic fibrosis and seven times that of Finland, the only other country reporting a childhood national rate. Incidence varied substantially between ethnicities. Most cases developed disease in early childhood and had delayed diagnosis.

Adolescent↗

Opposite metabolic changes in the habenula and ventral tegmental area of a genetic model of helpless behavior.

Congenitally helpless rats have been selectively bred to display an immediate helpless response to stress in order to model hereditary brain differences that contribute to depression vulnerability. Differences in regional brain metabolism between congenitally helpless and non-helpless rats were investigated using quantitative cytochrome oxidase histochemistry. The results indicated that congenitally helpless rats had 64-71% elevated metabolism in the habenula and a 25% elevation in the related interpeduncular nucleus. In contrast, helpless rats had 28% reduced metabolism in the ventral tegmental area (VTA) and 14-16% reductions in the basal ganglia and basolateral and central amygdala. The opposite metabolic changes in the habenula and ventral tegmental area may be especially important for determining the congenitally helpless rat's global pattern of brain activity, which resembles the metabolic activity pattern produced by dopamine antagonism.

Animals↗

Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.

PURPOSE: This study was carried out to show the effect of particle size reduction and bioadhesion on the dissolution and relative bioavailability of dicumarol. METHODS: Formulations were produced by a variety of methods including a novel technique to reduce particle size as well as phase inversion with poly(fumaric-co-sebacic)anhydride p(FA:SA) to create nanospheres. Drug was administered to groups of pigs and rats via oral gavage of a suspension, and dicumarol concentration in the blood was measured using a double extraction technique. RESULTS: In vitro results showed improved dissolution in both the micronized formulation and the encapsulated p(FA:SA) nanospheres. In vivo, relative bioavailability of a spray-dried formulation was increased by 17% in the rat and 72% in the pig by further reduction in particle size. The bioadhesive p(FA:SA) formulation also improved relative bioavailability over the spray-dried drug, increasing it by 55% in the rat and 96% in the pig. Additionally, the p(FA:SA) formulation prolonged Tmax and decreased Cmax in both species. CONCLUSION: This work demonstrates the importance of particle size and bioadhesion to improve oral bioavailability of ducumarol.

Adhesives↗

A catalogue of molecular, physiological and symbiotic properties of soybean-nodulating rhizobial strains from different soybean cropping areas of China.

We have analysed 198 fast-growing soybean-nodulating rhizobial strains from four different regions of China for the following characteristics: generation time; number of plasmids; lipopolysaccharide (LPS), nodulation factors (LCOs) and PCR profiles; acidification of growth medium; capacity to grow at acid, neutral, and alkaline pH; growth on LC medium; growth at 28 and 37 degrees C; melanin production capacity; Congo red absorption and symbiotic characteristics. These unbiased analyses of a total subset of strains isolated from specific soybean-cropping areas (an approach which could be called "strainomics") can be used to answer various biological questions. We illustrate this by a comparison of the molecular characteristics of five strains with interesting symbiotic properties. From this comparison we conclude, for instance, that differences in the efficiency of nitrogen fixation or competitiveness for nodulation of these strains are not apparently related to differences in Nod factor structure.

Bacterial Proteins↗

Dissociation of septo-hippocampal metabolism in the congenitally helpless rat.

Congenitally helpless rats, selectively bred to model features of endogenous depression, appear to have a paraventricular hypothalamic nucleus (PVH) that is markedly hyperactive. This study investigated septal and hippocampal regions purported to regulate the PVH. We found that cytochrome oxidase, an index of oxidative metabolism and neural activity, was significantly elevated in the hippocampus and subiculum of congenitally helpless rats. However, reduced activity was observed in the lateral and medial septal nuclei, the nucleus of the diagonal band, and the bed nucleus of the stria terminalis. This dissociation between hippocampal and septal activity may be a predisposing factor for the development of helpless behavior.

Animals↗

The effect of either a pre or post exercise stretch on straight leg raise range of motion (SLR-ROM) in females.

This study examined the order effect of a hamstring muscle stretch and resisted hamstring exercises on straight leg raise range of movement (SLR-ROM), in a group of twenty females aged 20-34 years. The stretch was applied either immediately before or Immediately after a resisted hamstring exercise. Exercise significantly decreased SLR-ROM (p < 0.05) and stretching significantly increased SLR-ROM (p < 0.05). The overall change in SLR-ROM for the two groups showed that a significant increase in SLR-ROM was detected (at a low force level) in Group 1 subjects who performed exercise and then stretched. A non-significant increase in SLR-ROM was detected by the higher force level in Group 1 subjects. In contrast, Group 2 subjects (stretch then exercise) showed a non-significant reduction in SLR-ROM at both levels of force.

Adult↗

Hypermetabolism of paraventricular hypothalamus in the congenitally helpless rat.

The congenitally helpless rat, selectively bred to model behavioral features of depression, has shown metabolic activity patterns in frontal and cingulate cortex similar to those detected in human imaging studies of depression and sadness. This study extends the same metabolic mapping technique (quantitative cytochrome oxidase histochemistry) to the hypothalamus, where activity levels were assessed in six nuclei: paraventricular nucleus, medial preoptic area, lateral hypothalamic area, supraoptic nucleus, suprachiasmatic nucleus, and ventromedial nucleus. Helpless rats were compared with a strain of non-helpless rats selectively bred for stress resistance. Only the paraventricular nucleus showed a significant group difference, with helpless rats showing elevated metabolism and non-helpless rats showing reduced metabolism relative to normal rats. Thus, paraventricular nucleus activity may be associated with genetic susceptibility to helpless behavior.

Animals↗

Genetic predisposition and the development of posttraumatic stress disorder in an animal model.

BACKGROUND: Exposure to extremely stressful events can lead to Posttraumatic stress disorder (PTSD). Due to the complexity of PTSD, animal models have been designed and advanced to address the role of psychosocial stressors in the etiology; however, the apparent role of genetics in susceptibility to PTSD-like behaviors in animals remains unexplored. METHODS: An animal model of congenital learned helpless (cLH) behavior has been used to study the effects of genetic disposition as a risk factor for the development of PTSD-like behaviors. Animals were monitored for changes in pain tolerance, spatial memory and hypothalamic-pituitary-adrenal functioning after re-exposure to intermittent stress in the presence and absence of situational cues. RESULTS: Exposure to stress resulted in an increase in pain tolerance in the cLH animals. In the spatial memory test 80% of the cLH animals manifested a decrease in performance after exposure to stress. These animals also had a blunted poststress corticosterone response. CONCLUSIONS: The genetic learned helpless animal model exhibited physiologic symptoms of analgesia, cognitive deficits and hyporesponsivity of the hypothalamic-pituitary-adrenal axis similar to those observed in human subjects with PTSD. It is proposed that the cLH model may be a valuable tool for exploring the role of genetic predisposition in the etiology of PTSD.

Animals↗

Transplantation of hepatitis C-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers.

A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus-positive (HCV(+)) donor livers for HCV(+) recipients. This study reviews the clinical outcome of a large series of HCV(+) recipients of HCV(+) liver allografts and compares their course with that of HCV(+) recipients of HCV-negative (HCV(-)) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV(+) transplant recipients were analyzed. Two groups were identified: a group of HCV(+) recipients of HCV(+) donor livers (n = 96), and a group of HCV(+) recipients of HCV(-) donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV(+) allograft (8.3% v 3.1%; P =.01). Patient survival showed a significant difference for the HCV(+) group compared with the HCV(-) group (90% v 77%; P =.01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV(+) group and only 1.3% in the HCV(-) group (P =.04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV(+) recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV(+) donor livers for transplantation in HCV(+) recipients safely and effectively expands the organ donor pool.

Female↗

Congenital helpless rats as a genetic model for cortex metabolism in depression.

The validity of congenital helplessness as a genetic rat model for human depression was investigated in cortical regions of the rat brain thought to be analogous to those showing abnormalities in human neuroimaging studies. Cortex metabolism was analyzed using quantitative cytochrome oxidase histochemistry. Congenital helpless rats showed changes in frontal and cingulate regions comparable to those that have demonstrated metabolic differences in human depression. Significant metabolic decreases were found in dorsal frontal, medial orbital, and anterior cingulate, whereas a significant increase was found in infraradiata (subgenual) cingulate. The direction of these changes were the same as those seen in human studies. These findings support the validity of congenital helplessness as a model for human depression.

Animals↗

Glutamate stimulation of raphe pallidus attenuates the cardiopulmonary reflex in anaesthetised rats.

Serotonin has been implicated as having a modulatory action on NTS neurones mediating vagal inputs controlling the cardiorespiratory system. Since raphe pallidus and raphe obscurus both send serotonergic projections to the NTS, we have investigated a neuromodulatory role for these structures on the cardiopulmonary reflex. A multibarrelled microelectrode positioned around the level of the area postrema was placed at varying depths into mid-line brainstem structures and the effect of glutamate stimulation on the cardiopulmonary reflex tested. Excitatory chemical stimulation in the region of raphe pallidus, but not raphe obscurus, attenuated significantly the respiratory and bradycardic components of the cardiopulmonary reflex. This attenuation was reversed by an NTS microinjection of RS-39604, a selective 5-HT, receptor antagonist. We propose that neurones in raphe pallidus that project to the NTS can release serotonin which acts via 5-HT4 receptors to attenuate the reflex phrenic nerve activity and heart rate components of the cardiopulmonary reflex.

Anesthesia↗

Hypertension and insulin resistant models have divergent propensities to learned helpless behavior in rodents.

The induction of learned helpless (LH) behavior in rats is a widely used model of unipolar depression. Recent studies have linked depression with hypertension and insulin resistance as observed in obesity, but the propensity of these disorders to manifest depression has not been reported. In this study, the LH behavioral paradigm was exploited in a model of hypertension (Dahl rat) and of insulin resistance (Zucker rat) to determine the propensity of these models to develop depression and to examine the profile of markers for the propensity of the cardiovascular system (plasma renin activity) and of the hypothalamus-pituitary-adrenal axis (corticosterone) in the display of propensity to depression. Results show that Zucker rats displayed the lowest propensity to the development of LH behavior (12%), followed by the control Sprague-Dawley rats (27%), and then Dahl rats (66%). In contrast, congenital learned helpless (cLH) rats, a genetically bred strain for animal depression, had the highest propensity (>90%). A gender effect was observed in the Zucker and cLH rats, with females showing an increased propensity to develop LH behavior. Plasma renin activity in the Dahl and Sprague-Dawley rats after the LH stress paradigm was not significantly different from baseline. In contrast, Zucker rats, with the lowest propensity to LH behavior, demonstrated a threefold increase in plasma renin activity after stress. Congenital LH rats, with the highest propensity to LH behavior, exhibited a significantly lower increase (43%) in plasma renin activity after stress. Hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis functioning correlated with propensity of LH behavior. Stress-induced corticosterone levels increased under twofold in cLH rats, whereas they increased more than sevenfold in Zucker rats. Taken together, these studies suggest that whereas genetically prone hypertensive rats have a very high propensity to depression, insulin-resistant rats have a profound resistance to depression. Moreover, a hyporesponsive HPA axis may be a marker for disorders that are comorbid with depression, whereas a hyperresponsive renin-angiotensin system may be indicative of resilience.

Animals↗

Regional size reduction in the human corpus callosum following pre- and perinatal brain injury.

This morphometric study examined two aspects of corpus callosum development: pediatric cortico-callosal topography and developmental neuroplasticity subsequent to perinatal brain injury. In vivo magnetic resonance imaging was used to quantify the total midsagittal cross-sectional area and five anterioposterior subregions of the callosum in 10 children with focal lesions and 86 healthy volunteer control subjects. Nine of the ten children with early injury showed a reduction in the total area of the callosum relative to matched controls. The area of the total callosum cross-section was inversely proportional to the size of lesion. All patients displayed region-specific size reduction. This regional thinning bore a topographical relationship to the lesion sites. Reduction in anterior subregions 1, 2 and 3 was respectively associated with lesions in the anterior inferior frontal area, the middle and superior frontal region, and the precentral area. Attenuation of subregion 4 corresponded to anterior parietal lesions, and thinning of subregion 5 occurred with posterior parietal injury. This cortical-callosal pattern coincides with adult and nonhuman primate mappings. Callosal thinning despite the early onset of the lesions suggests limits to developmental neuroplasticity.

Adolescent↗

Early stress and genetic influences on hypothalamic-pituitary-adrenal axis functioning in adulthood.

During early development, environmental challenges set the stage for permanent changes in the functioning of the pituitary-adrenal stress response. Since these data have been reported almost exclusively in single rat strains the role of phenotypic and genotypic factors in shaping the stress response is relatively unknown. This study examined whether the phenotypic/genetic profile of the rat influences the long-term response to challenge after early exposure to stress. Two strains of Sprague-Dawley rats were used in this study: one is a stress-induced animal model of "learned helpless" (LH) behavior and the other a resistant strain developed through selective breeding. Stress-induced adrenocorticotropic hormone (ACTH) and corticosterone release was monitored in adult congenital learned helpless (cLH) rats and congenital non-learned helpless (cNLH) rats. The rats were exposed to cold stress or maternal deprivation (on either postnatal day 7 or day 21). After the early acute stress exposure, animals remained undisturbed until challenged in adulthood (day 90) with footshock stress. In cLH animals (adults) early cold stress (particularly after acute stress on postnatal day 21) and maternal deprivation stress resulted in an enhancement of stress-induced ACTH release compared to nonstressed cLH and cNLH controls. In contrast, adrenal responsiveness was generally suppressed in cLH animals that were acutely stressed with cold stress or maternal deprivation stress early in life. The above results suggest that the genetic/phenotypic profile of the animal is a determinant in the changes observed in the adult stress response after early exposure to stressors.

Adrenocorticotropic Hormone↗

Increased basal activity of the HPA axis and renin-angiotensin system in congenital learned helpless rats exposed to stress early in development.

Learned helpless behavior has been successfully bred in rats and designated as a genetic animal model of human depression and/or anxiety. Since congenital learned helpless animals have an impaired stress response in adulthood, we examined the effects of early stressors (at postnatal day 7, 14 or 21) on the hypothalamic-pituitary-adrenal axis and the renin-angiotensin system. The functioning of the hypothalamic-pituitary-adrenal axis was monitored through changes in corticosterone plasma levels in the adult animals after acute exposure to cold stress and maternal deprivation early in development. Renin-angiotensin system functioning was assessed by plasma renin activity. Unstressed congenital learned helpless rats had corticosterone levels that were similar to control animals (congenital non-learned helpless rats not stressed during development), but unstressed plasma renin activity levels of congenital learned helpless rats were lower than congenital non-learned helpless rats. There was a step-wise increase in corticosterone plasma levels in the congenital learned helpless rats with age of acute presentation of either cold stress or maternal deprivation stress (day 7, 49%; day 14, 84%; and day 21, 543% for cold stress). However, these baseline corticosterone levels were significantly lower in congenital learned helpless rats compared to congenital non-learned helpless controls. Similarly, in response to early exposure to cold stress and maternal deprivation, there was an increase in plasma renin activity levels of congenital learned helpless rats with age of presentation to either stressors. However, this increase in plasma renin activity levels was not evident in congenital non-learned helpless controls. Taken together, these results suggest that exposure to stress early in development has long-term effects on both the hypothalamic pituitary-adrenal axis and the renin-angiotensin system, two neuroendocrine indicators of stress responsivity.

Animals↗

Molecular characterization of a toluene-degrading methanogenic consortium.

A toluene-degrading methanogenic consortium enriched from creosote-contaminated aquifer material was maintained on toluene as the sole carbon and energy source for 10 years. The species in the consortium were characterized by using a molecular approach. Total genomic DNA was isolated, and 16S rRNA genes were amplified by using PCR performed with kingdom-specific primers that were specific for 16S rRNA genes from either members of the kingdom Bacteria or members of the kingdom Archaea. A total of 90 eubacterial clones and 75 archaeal clones were grouped by performing a restriction fragment length polymorphism (RFLP) analysis. Six eubacterial sequences and two archaeal sequences were found in the greatest abundance (in six or more clones) based on the RFLP analysis. The relative abundance of each putative species was estimated by using fluorescent in situ hybridization (FISH), and the presence of putative species was determined qualitatively by performing slot blot hybridization with consortium DNA. Both archaeal species and two of the six eubacterial species were detected in the DNA and FISH hybridization experiments. A phylogenetic analysis of these four dominant organisms suggested that the two archaeal species are related to the genera Methanosaeta and Methanospirillum. One of the eubacterial species is related to the genus Desulfotomaculum, while the other is not related to any previously described genus. By elimination, we propose that the last organism probably initiates the attack on toluene.

Archaea↗

5-HT(4) receptors in nucleus tractus solitarii attenuate cardiopulmonary reflex in anesthetized rats.

We determined whether the cAMP-protein kinase A (PKA) pathway modulation of the cardiopulmonary reflex was caused by activation of 5-HT(4) receptors at the level of the nucleus tractus solitarii (NTS) of the anesthetized rat. NTS microinjection of 5-methoxytryptamine (5-MeOT, 2.25 pmol, n = 13), a 5-HT-receptor agonist, attenuated the cardiopulmonary reflex-evoked bradycardia and tachypnea. Microinjection of RS-39604 (4.5 pmol, n = 6), a selective 5-HT(4)-receptor antagonist, blocked the attenuating effect of 5-MeOT. NTS microinjection of 8-bromoadenosine 3', 5'-cyclic monophosphate (8-BrcAMP, 9 nmol, 45 nl, n = 10), a membrane-permeant analog of cAMP, significantly attenuated the reflex bradycardia and tachypnea. Rp-adenosine 3',5'-cyclic monophosphorothioate (4.5 nmol, n = 6), a cAMP-dependent PKA inhibitor, had no effect on the cardiopulmonary reflex when microinjected into the NTS alone but when given before a microinjection of either 8-BrcAMP (n = 6) or 5-MeOT (n = 6) blocked the attenuating effect on the reflex-evoked bradycardia. Thus stimulation of 5-HT(4) receptors within the NTS depresses the reflex bradycardia components of the cardiopulmonary reflex via a cAMP-dependent PKA pathway.

5-Methoxytryptamine↗