Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BNST) and its adrenergic input are key components in stress-induced reinstatement and maintenance of drug use. Intra-BNST injections of either beta-adrenergic receptor (beta-AR) antagonists or alpha2-adrenergic receptor (alpha2-AR) agonists can inhibit footshock-induced reinstatement and maintenance of cocaine- and morphine-seeking. Using electrophysiological recording methods in an in vitro slice preparation from C57/Bl6j adult male mouse BNST, we have examined the effects of adrenergic receptor activation on excitatory synaptic transmission in the lateral dorsal supracommissural BNST (dBNST) and subcommissural BNST (vBNST). Alpha2-AR activation via UK-14,304 (10 microM) results in a decrease in excitatory transmission in both dBNST and vBNST, an effect predominantly dependent upon the alpha2A-AR subtype. Beta-AR activation via isoproterenol (1 microM) results in an increase in excitatory transmission in dBNST, but not in vBNST. Consistent with the work with receptor subtype specific agonists, application of the endogenous ligand norepinephrine (NE, 100 microM) elicits two distinct effects on glutamatergic transmission. In dBNST, NE elicits an increase in transmission (62% of dBNST NE experiments) or a decrease in transmission (38% of dBNST NE experiments). In vBNST, NE elicits a decrease in transmission in 100% of the experiments. In dBNST, the NE-induced increase in synaptic transmission is blocked by beta1/beta2- and beta2-, but not beta1-specific antagonists. In addition, this increase is also reduced by the alpha2-AR antagonist yohimbine and is absent in the alpha2A-AR knockout mouse. In vBNST, the NE-induced decrease in synaptic transmission is markedly reduced in the alpha2A-AR knockout mouse. Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with beta-AR function.     

Haloperidol treatments increased macrophage activity in male and female rats: influence of corticosterone and prolactin serum levels.

Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

On the natural course of oral lichen lesions in a Swedish population-based sample

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.