Free choice ethanol intake of laboratory rats under different social conditions

To study the effects of different kinds of social deprivation on voluntary ethanol (ETOH) intake male Wistar rats were housed by (a) individual caging, (b) contact caging (partial social deprivation), and (c) group caging (four individuals per cage). In the latter condition the individuals were separated once a week from each other for 24 h. The rats simultaneously received water 5%, 10% and 20% ETOH for a period of 14 weeks. Additional control animals received water. Isolated individuals drank significantly more alcohol than group-housed or contact-caged rats. After a few days they preferred the 20% solution. Circadian measures revealed a discontinuous intake of high doses (> 0.5 g/kg/h) during short time periods. Contact-caged rats consumed much less ETOH, but both the preference for 20% ETOH and the circadian course of intake were similar to those occurring after isolation. ETOH intake of group-housed individuals was low. These individuals preferred the 5% solution and continuously consumed small ETOH doses. During the period of short-term isolation they drank even more ETOH than long-term isolated individuals. In contrast to the latter, the enhancement of intake decreased after some weeks. It is suggested that the differences between the housing groups not only reflect different degrees of isolation stress, but may also be explained by a contribution of different reinforcing or aversive psychotropic effects of ETOH. Reduction of isolation stress is probably most important in the situation of short term separation, whereas dose-dependent reinforcement via social stimulation or sedation may affect the drug taking behavior under the other social conditions.     

The inflammatory lesion of T cell line transferred experimental autoimmune encephalomyelitis of the Lewis rat: distinct nature of parenchymal and perivascular infiltrates

We have investigated the T cell receptor (TCR) repertoire in the inflammatory infiltrates of T line-transferred experimental autoimmune encephalomyelitis (EAE) of the Lewis rats. Using a panel of TCR V-specific monoclonal antibodies (mAbs) and immunocytochemistry, we studied the nature of the T cells entering the central nervous system (CNS) after transfer of either myelin basic protein (MBP)-reactive, or MBP-reactive but non-encephalitogenic T cell lines. All the MBP-specific T cell lines predominantely used the V8.2 TCR chain. T cell lines specific for the tuberculin purified protein derivative (PPD), using TCR V genes different from V8.2, served as controls. We first studied the time course of T cells entering the CNS. In all recipient rats, small, but significant numbers of -TCR-expressing infiltrate cells appeared in the CNS within the first 24 h after T cell transfer. In animals injected with either type of MBP-reactive T cells, the early infiltrate cells were preferentially located within the parenchyma of the spinal cord, while in PPD T lineinjected rats, the lymphocytes were mostly found in the meninges. TCR V gene usage was examined on the peak of clinical disease. Six days after T cell transfer, the TCR repertoire used by infiltrating lymphocytes in general seemed to be highly diverse. None of the V isotypes examined (i.e. V8.2, V8.5 or V10) was used by a major population of the -TCR-positive T cells. A more detailed, quantitative analysis of individual infiltrate compartments revealed, however, a preferential accumulation of V8.2-positive T cells within the parenchyma. In contrast, perivascular infiltrating cells used V genes randomly. Our results confirm first that activated T lymphocytes enter the brain rapidly irrespective of their antigen specificity. Second, the data show that most of the perivascular infiltrate T cells in the acute EAE lesion are host-derived, recruited presumably from the recirculating T cell pool, while the encephalitogenic, V8.2-positive T cells preferentially persist within the parenchyma.Abbreviations EAE experimental autoimmune encephalomyelitis - MBP myelin basic protein - TCL T cell line Supported by the Brazilian Research Council (CNPq)     

Variable CSF findings in early and late Lyme neuroborreliosis: A follow-up study in 47 patients

The cerebrospinal fluid (CSF) of 37 patients with early Lyme neuroborreliosis (ELN) and of 10 patients with late Lyme neuroborreliosis (LLN, duration of symptoms 7 months) was investigated for typical features differentiating between acute and chronic courses of disease. Individual patients were studied after 2 and 4 weeks, and 3, 6, and 12 months. Patients with ELN presented predominantly with symptoms of the peripheral nervous system, while patients with LLN generally suffered from symtoms of the central nervous system. At the first lumbar puncture, patients with ELN revealed a more intense pleocytosis in the CSF (P < 0.02) and a higher intrathecal synthesis of total IgM (P < 0.0003) and ofBorrelia burgdorferi-specific IgM antibodies (P < 0.01). At the same time, in patients with LLN, the blood-CSF barrier was more severely impaired (P = 0.03), and local production of total IgG (P = 0.0001), ofB. burgdorferi-specific IgG antibodies (P = 0.03) and of total IgA (P = 0.001) was more markedly increased. The quantity of intrathecally producedB. burgdorferi-specific IgA antibodies did not differ between the two study groups. Clinical recovery was usually accompanied by a considerable improvement of the blood-CSF barrier function and pleocytosis. After 6 months, the intrathecal synthesis of total IgG had significantly decreased in patients with ELN but not in those with LLN. At the same time, the CSF of most patients in both study groups still contained intrathecally producedB. burgdorferi-specific IgG antibodies. In the absence of clinical illness or symptoms of inflammation 6 and 12 months after treatment,B. burgdorferi-specific IgG antibodies in the CSF might simply indicate an anamnestic reaction to a previous infection of the central nervous system. Six months after antibiotic treatment, patients with ELN still revealed evidence of intrathecal synthesis of total IgM, whereas those with LLN did not. These antibodies, however, were not related toB. burgdorferi.     

Abbreviated cyclosporine AUCs on Neoral – the search continues!

 Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability. The pre-dose trough concentration (C_min) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced. However, the usefulness of Neoral C_min was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a greater impact on C_min than with classic cyclosporine. Secondly, C_min may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here, we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the 3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately 800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days. Received: 28 January 1998 / Revised: 10 June 1998 / Accepted: 15 June 1998     

Risk factors for mental disorder hospitalization after the Persian Gulf War: U.S. Armed Forces, June 1, 1991-September 30, 1993

Effects of Persian Gulf War (August 2, 1990–July 31, 1991) and Gulf War occupation on post-War hospitalization risk were evaluated through Cox proportional hazards modeling. Active-duty men (n = 1,775,236) and women (n = 209,760) in the Army, Air Force, Navy, and Marine Corps had 30,539 initial postwar hospitalizations for mental disorders between June 1, 1991 and September 30, 1993. Principal diagnoses in the Defense Manpower Data Center hospitalization database were grouped into 10 categories of ICD-9-CM codes. Gulf War service was associated with significantly greater risk for acute reactions to stress and lower risk for personality disorders and adjustment reactions among men. Personnel who served in ground war support occupations (men and women) were at greater risk for postwar drug-related disorders. Men who served in ground war combat occupations were at higher risk for alcohol-related disorders. Longitudinal studies of health, hospitalization, and exposure beginning at recruitment, are needed to better understand how exposure to combat affects the mental health of military personnel.     

Neurothekeoma palpebrae: a rare nerve sheath tumor arising in the eyelid

PURPOSE: To report a case of an eyelid neurothekeoma, a rare peripheral nerve sheath tumor. METHODS: Case report. RESULTS: An excisional biopsy, performed on a lesion removed from the upper eyelid of a 76-year-old woman, revealed the clinical and histopathologic features of a neurothekeoma, a tumor consisting of multiple collections of spindle cells in a myxomatous background. Immunohistochemical characterization showed positivity for NK1/C3, neuron-specific enolase, and alcian blue. CONCLUSION: Neurothekeoma palpebrae should be considered in the differential diagnosis of solitary nodules of the eyelids.