Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
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Carrier Proteins↗
Biomedical subjects
S Wilson
Publications and source records attributed to S Wilson.
Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
Animals↗
Tolerance to ischaemia and ischaemic preconditioning in neonatal rat heart.
Although there is much information on ischaemic preconditioning in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine the early development of cardiac tolerance to ischaemia and the possible protective effects of preconditioning, rat hearts isolated on days 1, 4 and 7 of postnatal life were perfused (Langendorff) with Krebs-Henseleit solution at constant pressure, temperature (37 degrees C) and rate (200 beats/min). Developed force (DF) of contraction was measured by an isometric force transducer, and analysed using an on-line computer. Hearts were exposed to 40 or 60 min of global ischaemia followed by 30 min of reperfusion. Preconditioning was induced by three 3-min periods of global ischaemia, each separated by 5-min periods of reperfusion. Developmental changes in expression of protein kinase C (PKC) isoforms, and their activation following preconditioning, were estimated using Western blot analysis. Recovery of contractile function during reperfusion decreased from day 1 (48 +/- 2%) to day 4 (42 +/- 1%) and day 7 (33 +/- 2%). Preconditioning failed to improve ischaemic tolerance on day 1 (46 +/- 2%) and on day 4 (43 +/- 3%), but pronounced effect was observed on day 7 (40 +/- 2%). Prolonging the period of sustained ischaemia from 40 to 60 min on day 1 did not lead to a better recovery of contractile function in preconditioned hearts. PKC isoforms alpha, delta, epsilon and zeta were expressed in the ventricular myocardium during the first week of life, but there was no evidence of translocation following preconditioning on day 7. It may be assumed that the decreasing tolerance of the heart to ischaemia during early postnatal life is counteracted by the development of an endogenous protection.
Animals↗
Estrogen and cancellous bone loss in the fowl.
Female birds model a type of woven bone prior to egg laying which is known as medullary bone. Medullary bone modeling is estrogen dependent and in the female fowl coincides with a decrease in cancellous bone volume. Medullary bone modeling was induced in male laying-strain fowl by the administration of estrogen and prevented in females by the administration of tamoxifen. In estrogen-treated males, medullary bone modeling was accompanied by cancellous bone loss; cancellous bone volume was significantly lower than in control males (P < 0.001). In females, the prevention of medullary bone modeling by tamoxifen treatment resulted in significantly higher cancellous bone volumes than in control females (P < 0.001). Estrogen therefore appears to play a role in cancellous bone loss in the fowl.
Animals↗
Variation in cerebral perfusion pressure with different hypertensive states in pregnancy.
OBJECTIVE: Our purpose was to compare the estimated maternal cerebral perfusion pressure and an index of vascular resistance, the resistance area product, in nonpregnant women with hypertensive pregnant women. STUDY DESIGN: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasonography in 17 nonpregnant women, 17 pregnant normotensive patients, 20 pregnant patients with chronic hypertension, and 21 pregnant patients with pre-eclampsia (defined by The American College of Obstetricians and Gynecologists criteria) and cerebral blood flow velocities were determined. We calculated estimated cerebral perfusion pressure as [Estimated cerebral perfusion pressure = V mean/(V mean = V diastolic) (Mean blood pressure - Diastolic blood pressure)] modified from Aaslid et al, 1986. Because the diameter of the vessels could not be measured directly, an index of resistance, the resistance area product, was calculated. Resistance area product = Mean blood pressure/mean velocity (Evans et al, 1988). We calculated an index of cerebral blood flow (Cerebral blood flow index) = Estimated cerebral perfusion pressure/resistance area product. RESULTS: Women who were chronically hypertensive and those with pre-eclampsia showed a significant increase in estimated cerebral perfusion pressure and resistance area product compared with nonpregnant and pregnant normotensive women. An estimate of cerebral blood flow (cerebral blood flow index) in nonpregnant women showed that pregnancy resulted in a nonsignificant 18% increase in cerebral blood flow. CONCLUSIONS: Women with chronic hypertension and pre-eclampsia behave similarly by demonstrating significant increases in cerebral perfusion pressure (estimated cerebral perfusion pressure) and cerebrovascular resistance (resistance area product) compared with normotensive and nonpregnant women. Pregnant patients have a minimal increase in cerebral blood flow (18%).
Adult↗
Effect of labor on maternal cerebral blood flow velocity.
OBJECTIVE: Our purpose was to determine the effect of contractions and second-stage pushing on cerebral blood flow velocity as an indirect assessment of cerebral hemodynamic changes during labor and delivery. STUDY DESIGN: A prospective cohort of 15 normotensive patients in early labor had maternal middle cerebral blood flow velocity assessed continuously with transcranial Doppler ultrasonography. Assessment was performed during the peak of a contraction, during the trough of a contraction, and with pushing in the second stage. We assessed systolic, diastolic, mean cerebral blood flow velocity (in centimeters per second), and pulsatility index over four contractions. We used analysis of variance to compare velocities at these three stages. RESULTS: Mean maternal cerebral blood flow velocity fell significantly (61.2 +/- 6.4, 50 +/- 10.2, 52.2 +/- 6.5 cm/sec) (p < 0.008). Pulse rate rose significantly by 16 beats/min (p < 0.0001), but no significant change in blood pressure occurred in patients during second-stage labor when pushing. CONCLUSIONS: Middle cerebral vessels vasodilated during the peak of contractions and second-stage pushing as assessed by transcranial Doppler ultrasonography. Pushing in the second stage with the Valsalva maneuver does not expose the patient to a greater risk for middle cerebral vasospasm than contractions developing in the first stage.
Analysis of Variance↗
Changes in cerebral perfusion pressure in puerperal women with preeclampsia.
OBJECTIVE: To determine the variation in the estimated maternal cerebral perfusion and cerebrovascular resistance (the resistance area product) in the puerperium. METHODS: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasound in ten women 2 days before labor, in 21 women in early labor and at 24 and 48 hours postpartum, and in 6 women at 1 week postpartum. Cerebral blood flow velocities were determined. Women were diagnosed initially with mild preeclampsia. Estimated cerebral perfusion pressure was Vmean/[Vmean - Vdiastolic] [BPmean - BPdiastolic]. Because the diameter of the vessels could not be measured directly, an index of resistance was calculated: the resistance area product = BPmean/velocitymean. We calculated an index of cerebral blood flow to be estimated cerebral perfusion pressure divided by resistance area product. Our study had a power of 80% to detect a 16-cm/second increase in middle cerebral blood flow velocity. RESULTS: Estimated maternal cerebral perfusion was maintained for up to 1 week postpartum. Cerebrovascular resistance did not change in the puerperium. Cerebral blood flow index (+/-standard deviation) was significantly increased at 1 week postpartum compared with early labor levels (28.3 +/-6.9 versus 46.7+/-15.6, respectively) (P < .05). CONCLUSION: Cerebral blood flow 1 week postpartum increased significantly over early labor values. These persistent changes in the cerebral vasculature might put patients at risk for seizures up to 1 week postpartum.
Adult↗
Orphan G-protein-coupled receptors: the next generation of drug targets?
The pharmaceutical industry has readily embraced genomics to provide it with new targets for drug discovery. Large scale DNA sequencing has allowed the identification of a plethora of DNA sequences distantly related to known G protein-coupled receptors (GPCRs), a superfamily of receptors that have a proven history of being excellent therapeutic targets. In most cases the extent of sequence homology is insufficient to assign these 'orphan' receptors to a particular receptor subfamily. Consequently, reverse molecular pharmacological and functional genomic strategies are being employed to identify the activating ligands of the cloned receptors. Briefly, the reverse molecular pharmacological methodology includes cloning and expression of orphan GPCRs in mammalian cells and screening these cells for a functional response to cognate or surrogate agonists present in biological extract preparations, peptide libraries, and complex compound collections. The functional genomics approach involves the use of 'humanized yeast cells, where the yeast GPCR transduction system is engineered to permit functional expression and coupling of human GPCRs to the endogenous signalling machinery. Both systems provide an excellent platform for identifying novel receptor ligands. Once activating ligands are identified they can be used as pharmacological tools to explore receptor function and relationship to disease.
Animals↗
Review of computerized decision support systems for oral anticoagulation management.
Computerized decision support systems (CDSS) are available to assist clinicians in the therapeutic management of oral anticoagulation. We report the findings relating to CDSS for oral anticoagulation management of a primary-care-based systematic review which largely focused on near-patient testing. Seven papers were reviewed which covered four different systems. The methodology of these papers was generally poor, although one randomized controlled trial showed improved therapeutic control associated with computerized management compared with human performance.
Administration, Oral↗
Maternal middle cerebral artery velocity changes in HELLP syndrome versus pre-eclampsia.
Our objective was to determine whether there is a difference in middle cerebral artery blood flow velocity in patients with the syndrome of hemolysis, elevated liver enzymes and low platelet counts (HELLP syndrome) compared to a matched controlled group of patients with pre-eclampsia and without HELLP syndrome. Six pre-eclamptic patients with HELLP syndrome and 12 pre-eclamptic women without HELLP syndrome had maternal middle cerebral artery blood flow velocity assessed antepartum and at 24 and 48 h postpartum. We compared the effect of the development of HELLP syndrome on middle cerebral artery blood flow velocity changes using non-parametric tests. Patients with HELLP syndrome showed no significant differences in diastolic, systolic, mean middle cerebral artery blood flow velocity or pulsatility index in either the antepartum or 24-h and 48-h postpartum phases when compared to non-HELLP pre-eclamptic patients. Our data suggest that there is no difference in the blood flow velocity waveform of the maternal middle cerebral artery between patients with pre-eclampsia and those with HELLP syndrome.
Adult↗
The role of Gulf Coast oysters harvested in warmer months in Vibrio vulnificus infections in the United States, 1988-1996. Vibrio Working Group.
Vibrio vulnificus infections are highly lethal and associated with consumption of raw shellfish and exposure of wounds to seawater. V. vulnificus infections were reported to the Centers for Disease Control and Prevention from 23 states. For primary septicemia infections, oyster trace-backs were performed and water temperature data obtained at harvesting sites. Between 1988 and 1996, 422 infections were reported; 45% were wound infections, 43% primary septicemia, 5% gastroenteritis, and 7% from undetermined exposure. Eighty-six percent of patients were male, and 96% with primary septicemia consumed raw oysters. Sixty-one percent with primary septicemia died; underlying liver disease was associated with fatal outcome. All trace-backs with complete information implicated oysters harvested in the Gulf of Mexico; 89% were harvested in water >22 degrees C, the mean annual temperature at the harvesting sites (P < .0001). Control measures should focus on the increased risk from oysters harvested from the Gulf of Mexico during warm months as well as education about host susceptibility factors.
Adolescent↗
Laparoscopic removal of a right adrenal pheochromocytoma in a pregnant woman.
Pheochromocytomas are a rare cause of hypertension in pregnancy. Laparoscopic adrenalectomy has been used effectively and safely in nonpregnant patients with pheochromocytoma, with the resultant benefits to the patients of less postoperative pain, shorter hospital stay, and quicker return to normal activities than is associated with open techniques. This represents the first report of a laparoscopic adrenalectomy for pheochromocytoma in a pregnant woman. Issues that are unique to laparoscopic surgery in pregnant patients are discussed.
Adrenal Gland Neoplasms↗
Restoring homeostasis in a residential care facility through behaviour modification.
A verbally aggressive, 32-year-old male with a traumatic brain injury was admitted to a unit in an aged care facility for residential care. The homeostasis of the unit was disrupted by the resident's verbal aggression and other inappropriate behaviours. With the guidance of a neuropsychologist, nursing staff were able to use behaviour modification to successfully replace the disruptive behaviours with more socially appropriate ones. A series of positive rewards was implemented in response to socially appropriate behaviour, whilst inappropriate behaviours received a negative reward. Several disruptive behaviours were affected by the single treatment implemented. This interdependence of targeted behaviours was viewed as a clinical advantage, as it served to provide a more rapid restoration of homeostasis to the unit. The use of a single-subject, multiple baseline design in this case study demonstrates that disruptive behaviours may be reversible.
Adult↗
Should relatives be allowed in the resuscitation room?
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Attitude of Health Personnel↗
IgA nephropathy in psoriasis.
IgA nephropathy (IGAN) was first described by Berger and Hinglais in 1968. It is now the most common glomerular disease worldwide. IGAN has been associated with several diseases. Its association with psoriasis has been rarely described. We report a case of IGAN with crescentic changes, associated with psoriasis vulgaris. We review the literature on the association of IGAN with psoriasis and discuss the likely pathogenetic linkage.
Adult↗
Integrating the cognitive and physiological aspects of craving.
'Craving is generally considered a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment'-ARC expert consensus (Pickens and Johanson, Drug and Alcohol Dependence 30: 127-131). There are however difficulties in defining craving and urges to use drugs and in associating craving with drug use and relapse. Tiffany [Psychological Review 97(2): 147-168] has reviewed a considerable number of studies that associated reports of craving with consumption measures of drugs and revealed only an overall modest correlation of 0.4. These findings call into question the general assumption that subjective cravings are invariably associated with drug use. Furthermore, it led to Tiffany's provocative argument that cravings are not necessary for drug use. We have addressed these issues by using a range of complementary techniques derived from research in related fields such as the cognitive psychology of anxiety and depression, physiological response measurements and positron emission tomography (PET) neuro-imaging. Initially we developed computerized assessments to probe cognitive dysfunction in addiction that related to biased processing of automatic thoughts and beliefs about craving and drug use in opiate-dependent subjects and alcoholics. Subsequently in an attempt to develop a reliable method of inducing craving we explored an imagery-based technique that relied on the memory of craving experiences. These experiments were conducted both in opiate addicts who had achieved abstinence and in those undergoing detoxification. Finally, we have begun a study to understand the neural mechanisms of craving using imagery-based procedures at the same time as performing PET studies of regional blood flow using the O15-labelled water technique.
Alcoholism↗
Pindolol augmentation of sertraline in resistant depression and its effect on sleep.
A case is reported of a 34-year-old lady with a 2-year history of resistant depression who responded to pindolol augmentation of sertraline. It also illustrates the use of sleep electroencephalogram measures as a way of assessing changes in brain 5-hydroxytryptamine function.
1-Naphthylamine↗
Gadolinium chloride toxicity in the mouse.
1. Groups of five male and five female CD-1 mice received a single intravenous injection of gadolinium chloride at dosages of 0 (saline control), 0.05, 0.1 and 0.2 mmol/ kg. All mice were necropsied 48 h post dose. 2. Plasma analysis showed increases in concentrations of lactate dehydrogenase (both sexes), aspartate aminotransferase and alanine aminotransferase (females only) in the 0.2 mmol/kg group. Cholesterol was elevated at all dosages in both sexes whilst globulin was raised in both sexes at 0.1 and 0.2 mmol/kg. 3. Histological lesions were present at all dosages and increased in severity in a dose-related fashion. The most common lesions were: mineral emboli in capillaries, accumulation of mineral in the mononuclear phagocytic system, hepatocellular necrosis, and lymphoid depletion, necrosis and mineralisation in the spleen. 4. Such observations are similar to those in rats given gadolinium chloride and should be assessed when evaluating the toxicological profile of gadolinium containing compounds being developed for nuclear magnetic resonance imaging.
Alanine Transaminase↗