Altered central micro-opioid receptor binding after psychological trauma.

BACKGROUND: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing. METHODS: Here we examined the micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n = 14) and without combat exposure (n = 15). Differences in micro-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions. RESULTS: Relative to healthy controls, both trauma-exposed groups had lower micro-opioid receptor BP2 in extended amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior cingulate cortex compared with both control groups. Micro-opioid receptor BP2 in combat-exposed subjects without PTSD was lower in the amygdala but higher in the orbitofrontal cortex compared with both PTSD patients and healthy controls. CONCLUSIONS: These findings differentiate the general response of the micro-opioid system to trauma from more specific changes associated with PTSD.     

Nitric oxide synthase inhibitor,nitro-iminoethyl-L-ornithine,reduces ischemia-reperfusion injury in rabbit skeletal muscle

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 μM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 μM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. © 1994 Wiley-Liss, Inc.     

Could proteinuria evaluation be helpful in predicting renal progression in apolipoprotein E-deficient (E-/-) mice with chronic renal failure?

Sir, We read with interest the recent article by Buzello et al. [1]on renal changes in apo E^-/- mice after subtotal nephrectomy.They compared renal lesion development in male wild-type C57BL/6mice with that of genetically modified male apo E^-/- mice aftereither sham operation, unilateral nephrectomy or subtotal nephrectomy(SNX) by removal of 75% of the cortex in one kidney and removalof the contralateral kidney. They found     

Monoclonal antibodies against carcinoembryonic antigen (CEA) used in a solid-phase enzyme immunoassay. First clinical results

A solid-phase enzyme immunoassay using both mouse monoclonal and goat polyclonal antibodies against carcinoembryonic antigen (CEA) was developed. The assay detects 0.6 to 1.2 ng of CEA per ml of serum and has 3 incubation steps which can be performed in 1 day. Polystyrene balls coated with polyclonal goat anti-CEA antibodies are first incubated with heat-extracted serum samples. Bound CEA is then detected by addition of mouse monoclonal antibodies, followed by goat IgG anti-mouse IgG1 coupled to alkaline phosphatase. Results with this enzyme immunoassay using monoclonal antibodiies (M-EIA) have been compared with those obtained by the conventional inhibition radioimmunoassay (RIA) using goat antiserum. Three hundred and eighty serum samples from 167 patients with malignant or non-malignant diseases and from 134 normal individuals with or without heavy smoking habits were analyzed by the 2 assays. Excellent correlation between the results of the 2 assays was obtained, but the M-EIA, using monoclonal antibodies from a single hybridoma, did not discriminate better than the conventional RIA between CEA produced by different types of carcinoma and between CEA associated with malignant or non-malignant diseases. Follow-up studies of several patients by sequential CEA determinations with the 2 assays showed that the M-EIA was as accurate as the RIA for the detection of tumor recurrences.     

Evaluation of three substitutes for Percoll in sperm isolation by density gradient centrifugation

Silane-coated silica particle solutions (ISolate(TM) and PureSperm)TM)) and iodixanol (OptiPrep(TM)) were compared to polyvinylpyrrolidone (PVP)-coated silica particles (Percoll(TM)) in their efficacy to recover spermatozoa by gradient centrifugation for use in assisted reproductive procedures. Efficacy was assessed in terms of percentages of sperm recovery, sperm vitality and motility, normal sperm morphology and normal sperm chromatin condensation. No significant difference was found in the recovery of spermatozoa for men with both normal sperm counts and oligozoospermia, between PVP-coated and silane-coated particle solutions. Iodixanol had significantly lower sperm recovery compared to the other products. Sperm vitality, progressive motility, normal morphology and normal chromatin condensation did not differ significantly between any of the sperm isolation products.      

Secretion of monocyte chemotactic activity by alveolar macrophages.

The purpose of this study was to determine if alveolar macrophages (AMs) are a source of monocyte chemoattractants and the role bleomycin interaction with AMs may play in the recruitment of monocytes to the lung in a rodent model of bleomycin-induced pulmonary fibrosis. AMs isolated from rats with bleomycin-induced fibrosis secreted significantly greater amounts of monocyte chemoattractants than those isolated from normal rats. When AMs from normal rats were stimulated with bleomycin in vitro, monocyte chemotactic activity was secreted into the medium. Chemotactic activity secretion by AM stimulated with 0.01 to 0.1 micrograms/ml bleomycin was significantly higher than that of cells incubated in medium alone. This activity was truly chemotactic for monocytes, but caused only minimal migration of normal AMs. Bleomycin itself at concentrations of 1 pg/ml to 10 micrograms/ml had no monocyte chemoattractant activity. Characterization of the chemotactic activity in conditioned media (CM) from bleomycin-stimulated AM demonstrated that the major portion of the activity bound to gelatin, was heterogeneous, with estimated molecular weights of 20 to 60 kd, and was inactivated by specific antifibronectin antibody. These findings suggest that fibronectin fragments are primarily responsible for the monocyte chemotactic activity secreted by AMs. Through increased secretion of such chemotactic substances, AMs could play a key role in the recruitment of peripheral blood monocytes into the lung in inflammatory lung disease and fibrosis.