Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR141716A

We evaluated delta-9 tetrahydrocannabinol (Delta9-THC), delta-8 tetrahydrocannabinol (Delta8-THC), CP55,940 (CP55), 1-deoxy-11-hydroxy-Delta8-THC-dimethylheptyl (deoxy-HU210, a CB2-selective cannabinoid that also binds the CB1 receptor) and the endogenous cannabinoid anandamide (ANA) via i.c.v. and/or intrathecal (i.t.) routes of administration, alone and in combination with SR141716A (SR), a CB1 antagonist, using the tail-flick test. Our studies were performed in order better to characterize potential diversity in interactions of the cannabinoids with the cannabinoid (CB1) receptor. When SR was administered i.c.v. or i.p. before Delta9-THC, Delta8-THC or CP55 (i.c.v. or i.t.), SR was a potent antagonist and the blockade was complete (AD50 相似文献   

Concomitant therapy with anxiolytics or hypnotics and maintenance of initial SSRI therapy

BACKGROUND: Depletion of fat-free mass (FFM) occurs in a considerable number of patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The goal of the study was to determine whether dual-energy X-ray absorptiometry (DXA) is an applicable method in the clinical evaluation of body composition in COPD. DESIGN: In a cross-sectional study in 79 COPD patients participating in a pulmonary inpatient program and in 23 healthy volunteers, DXA was compared with deuterium dilution (Deu) in the estimation of FFM. Bone mineral density (BMD), a DXA measurement, was also compared between the 2 groups. RESULTS: FFM(DXA) was highly related to FFM(Deu) in men (R2 = 0.93, P < 0.001) and women (R2 = 0.91, P < 0.001). On average, DXA resulted in higher FFM values than did Deu in COPD patients (3.4 kg; P < 0.001) and in healthy volunteers (2.1 kg; P < 0.001). Furthermore, the intramethod difference in FFM was higher in men than in women in the COPD group (P < 0.05) and in healthy volunteers (P < 0.001). BMD was lower in the COPD group than in the healthy, age-matched volunteers (P < 0.001). In 56% of the COPD patients, there were indications of bone mineral loss, defined as a BMD <1 SD of a matched reference population provided by the software. BMD was <2 SDs in 36% of the COPD patients. CONCLUSIONS: DXA appears to be a suitable alternative method to Deu for assessing body composition and is also of value in identifying bone mineral loss in COPD patients, and is therefore applicable in the clinical evaluation of these patients.     

Likelihood-based inference for the genetic relative risk based on affected-sibling-pair marker data

The unique structure, role and operations of government high-security (HS) laboratories which work on animal diseases are described, with particular reference to the laboratories of nine countries. High-security laboratories provide cost-effective insurance against catastrophic losses which could occur following exotic disease outbreaks. The importance of these laboratories is reflected in the fact that several new laboratories have recently been constructed at considerable expense and older facilities have undergone major renovations. Biosecurity is fundamental to the operation of high-security laboratories, so good facility design and microbiological security practices are very important. High-security laboratories conduct exotic disease diagnosis, certification and surveillance, and also perform research into virology, disease pathogenesis and improvements to diagnostic tests and vaccines. The mandate of these laboratories includes the training of veterinarians in the recognition of exotic diseases. One extremely important role is the provision of expert advice on exotic diseases and participation (both nationally and internationally) in policy decisions regarding animal disease issues.     

A study of a highly specific pyroglutamyl aminopeptidase type-II from the membrane fraction of bovine brain

The purpose of these experiments was to define the topography of cuneate and spinal projections to the forelimb representation in the rostral dorsal accessory olive (rDAO). We were interested in determining whether the spinal and cuneate inputs constitute a homogeneous afferent source, and whether there is evidence that they serve different functional roles. We were also interested in determining whether the somatotopy of rDAO is the result of a point-to-point projection from its afferent sources, or whether the projection suggests a reorganization of afferents at the olive. Single unit recording was used to identify specific regions of rDAO, and the topography of inputs to the identified regions was determined by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a tracer. The results from retrograde tracing were confirmed by using WGA-HRP as an anterograde tracer from input sources. The cuneate and spinal neurons providing input to rDAO constitute two distinct neural populations. One consists of cells in the caudal cuneate nucleus and lamina VI of the rostral two cervical segments, the other consists of cells in the rostral cuneate nucleus. The cells in the caudal cuneate nucleus and the rostral cervical segments are large, multipolar neurons that form a single column of rDAO input cells. The column of cells projects to the contralateral rDAO in a topographic fashion with rostral regions of the column projecting to rostral rDAO, which contains cells that respond to somatosensory stimulation of the contralateral shoulder, trunk, and proximal forelimb. Caudal regions of the column project to caudal rDAO, which contains cells that respond to stimulation of the distal forelimb. Despite this topography, there is a large degree of overlap in the terminations from neighboring regions of the input column, indicating that a major reorganization occurs at the rDAO. The projection from the rostral cuneate nucleus arises from small neurons that project bilaterally to rDAO, and the input from the rostral cuneate nucleus lacks a clear topography. We propose that input from the cell column is responsible for the somatosensory sensitivity of rDAO neurons, whereas input from rostral cuneate is most likely modulatory, probably inhibitory, in nature.     

Do amoebic liver abscesses start as large lesions? Case report of an evolving amoebic liver abscess

Paired tympanic membrane and rectal temperatures were compared for 103 female fallow deer (Dama dama) after short-term anesthesia to determine if tympanic temperature was a reliable indicator of hyperthermia associated with handling stress. Each deer was restrained in a drop-floor chute, anesthetized by i.v. injection of xylazine hydrochloride and ketamine hydrochloride, and removed from the chute. After a short procedure was completed, i.m. antibiotics and i.v. yohimbine hydrochloride were given to each deer. Temperature measurements were obtained during recovery from anesthesia, approximately 10 min after initial restraint. Mean tympanic temperature (38.6 degrees C +/- 0.7 degrees C; range 37.4-40.8 degrees C) was significantly lower than mean rectal temperature (40.1 degrees C +/- 0.8 degrees C; range 37.5-42.0 degrees C) [corrected]. One animal had rectal and tympanic temperatures of 42.0 degrees C and 40.8 degrees C, respectively, but regained normal body temperature after cooling measures were applied. Tympanic membrane temperature measurement may provide a method for evaluation of body temperature by separating retained body heat caused by exertion from critical elevations in core body temperature associated with clinical disease or capture stress.     

Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET

Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetised rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100mg/kg i.p.) resulted in an increase in [11C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitisation was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170mg/kg/day). In the course of acute L-DOPA treatment (20mg/kg), extracellular GABA levels were reduced by approximately 20% in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease.     

Endoscopic management of choledocholithiasis: to cut, stretch or relax?

Since it was first described in 1974, endoscopic sphincterotomy has been the procedure of choice for management of choledocholithiasis, especially for retained common bile duct stones. However, it has the dubious distinction of being the most hazardous of all endoscopic retrograde cholangiopancreatographic procedures and carries an immediate complication rate of 8-10%. Concern has also been voiced about the long-term complications of sphincterotomy, as the sphincter of Oddi is cut during the procedure. To prevent, or at least lessen, the short- and long-term complications of endoscopic sphincterotomy, an alternative in the form of balloon dilatation of the papilla, has been advocated. However, the procedure of balloon dilatation is cumbersome, time consuming and, more importantly, a recent multi-centre study from the US comparing endoscopic sphincterotomy with balloon dilatation observed higher complications with balloon dilatation. The use of nitrites to relax the papilla is another novel method used for removal of common bile duct calculi. So how should a therapeutic endoscopist decide which method is to be used? The advantage of endoscopic sphincterotomy is that it has been around for more than two decades and most endoscopists are familiar with the technique as well as its complications. It can be accomplished quickly and with the advent of wire-guided and balloon-mounted sphincterotomes, the time taken for the procedure to be completed has been reduced further. The complications of the procedure are less when it is employed for removal of common bile duct stones and when used by experts. It, therefore, still appears to be the procedure of choice for endoscopic management of choledocholithiasis. The other two methods may, however, be useful in patients with coagulopathy.     

Cytological characteristics, elemental composition of alveolar macrophages from bronchoalveolar lavage, lung pathology in liquidators of the consequences of the accident at the Chernobyl power plant

Tuberculosis is an ancient disease which has had a resurgence in the United States. Many elderly clients were exposed to tuberculosis as children and young adults and are still carrying the infection today. This article describes tuberculosis as it affects the elderly client in community and nursing home settings. The history, etiology, clinical manifestations, treatment, and prevention of tuberculosis infection and disease are presented. Because nurses can be very instrumental in controlling tuberculosis in the elderly, gerontological nursing implications are discussed.     

Cardiotoxicity of chlorodibromomethane and trichloromethane in rats and isolated rat cardiac myocytes

The cardiovascular effects were investigated after acute and subacute treatment with chlorodibromomethane (CDBM; 0.4 to 3.2 mmol/kg p.o.), trichloromethane (TCM; 0.31 and 1.25 mmol/kg p.o.) and mixtures of CDBM and TCM (acute, 0.8 mmol CDBM/kg + 1.25 mmol TCM/kg p.o.; subacute, 0.4 mmol CDBM/kg + 0.31 mmol TCM/kg p.o.) in conscious and urethane anaesthetized male Wistar rats (n = 6-10 per treatment). Furthermore it was observed whether cardiovascular responses were modified in CDBM or TCM treated rats after administration of exogenous catecholamines (epinephrine, 1 microg/kg; norepinephrine, 2 microg/kg) and underpinned with in vitro alterations of Ca2+ dynamics in cardiac myocytes. The present findings demonstrated that single and subacute oral administration of CDBM or TCM and mixtures of CDBM and TCM resulted in arrhythmogenic and negative chronotropic and dromotropic effects in conscious and urethane anaesthetized rats. The atrioventricular conduction time and the intraventricular extension time were extended. A slight shortening of the repolarization velocity was observed. The myocardial contractility was depressed and the heart was sensitized to the arrhythmogenic effects of epinephrine. After catecholamine injection the adrenergic cardiovascular responses in urethane anesthetized rats were modified: increased hypertensive epinephrine and norepinephrine action as well as augmentation of negative chronotropic and negative dromotropic cardiac effects of catecholamines were observed. The positive inotropic adrenergic response was diminished. The present in vivo findings, myocardial depression after acute CDBM treatment, as determined by different indices of contractility, correlate well with the observed inhibitory actions of CDBM on Ca2+ dynamics in isolated cardiac myocytes. All cardiovascular alterations found after CDBM or TCM treatment were not intensified after treatment with mixtures of CDBM and TCM. The effects observed were distinctly stronger after TCM (1.25 and 0.31 mmol/kg) treatment compared to CDBM (0.8 and 0.4 mmol/kg) treatment.