Trypsin and rosmarinic acid reduce the toxicity of Micrurus fulvius venom in mice.

UNLABELLED: CONTEXT. Antivenom is expensive and not always available, so alternative treatments are being investigated. OBJECTIVE. The efficacy of trypsin or rosmarinic acid (RA) in treating Micrurus fulvius in a murine model is determined. MATERIALS AND METHODS. DESIGN: randomized controlled blinded study. SUBJECTS: Fifty mice (20-30 g). Study groups: Intraperitoneal injections of: 1) 2 mg/kg M. fulvius venom (approximately twice the LD50 for mice; n = 10); 2) 2 mg/kg M. fulvius venom incubated in vitro for 1 h prior to injection with RA at a 1:10 ratio (n = 17); 3) 2 mg/kg M. fulvius venom incubated in vitro for 1 h prior to injection with 1 mg of trypsin (n = 17); 4)1 mg trypsin IP without venom (n = 3); and 5) RA IP without venom (n = 3). MAIN OUTCOME: time to toxicity (respiratory distress (< 25 breaths/min.), loss of spontaneous locomotor activity, or inability to upright self). STATISTICAL ANALYSIS: Time to toxicity using Tukey-Kramer HSD; Survival to 4, 6, and 12 h using Chi-square analysis. RESULTS. Onset of toxicity: venom + saline, 120.3 + 64.4 min; venom + rosmarinic acid, 238.1 ± 139.2 min (p = 0.15 relative to venom + saline); venom + trypsin, 319.7 + 201.0 min (p = 0.007 relative to venom + saline). Venom + trypsin but not venom + RA survival to 4 h was significant compared to venom + saline (p = 0.023). Two mice in the venom + trypsin group and one mouse in the venom + RA group survived to 12 h. Mice receiving trypsin without venom or RA without venom survived to 12 h without toxicity. Discussion. This work suggests that trypsin and RA may have efficacy in treatment M. fulvius envenomation. CONCLUSION. In vitro neutralization of M. Fulvius venom by trypsin justifies progressing to an in vivo model in future studies.

Similar T-cell oligoclonality in antimitochondrial antibody-positive and -negative primary biliary cirrhosis.

Approximately 5% of patients with clinical and histological features suggestive of primary biliary cirrhosis do not have anti-mitochondrial antibodies that can be detected by current methodologies. Although the role of these autoantibodies in the pathogenesis of liver disease is uncertain, T lymphocytes within the portal tracts are felt to be important mediators of bile duct destruction. In order to investigate the hypothesis that a similar T-cell process may be involved in both antimitochondrial antibody-positive and -negative primary biliary cirrhosis, we characterized the oligoclonally expanded T cells in both types of patients by analysis of complementarity determining region 3 length in peripheral blood mononuclear cells. The distribution of oligoclonally expanded T cells was similar in both groups. This finding does not support a distinct T-cell-mediated pathogenesis for anti-mitochondrial antibody-positive and -negative primary biliary cirrhosis but rather suggests that similar processes may be involved in the immunopathogenesis of both.

Mycobacterium tuberculosis infection in the acquired immunodeficiency syndrome. A review of 14 patients.

The clinical findings in 13 drug abusers and one homosexual man with tuberculosis and the acquired immunodeficiency syndrome (AIDS) from New York City are described. Tuberculosis preceded the diagnosis of AIDS in nine of the 14 patients by a mean of 7 months and occurred within the same month in the remaining five. The presence of thrush, generalised lymphadenopathy, lymphopenia, cutaneous anergy and chest radiographs showing hilar adenopathy and/or lower lobe infiltrates was common among the patients in whom tuberculosis preceded AIDS. Eight of our patients had extra-pulmonary tuberculosis, six had disseminated tuberculosis and five had tuberculous lymphadenitis. Cultures of tissue biopsies may be positive for Mycobacterium tuberculosis despite the absence of acid fast bacilli or granulomas on microscopic examination. Tuberculosis generally responded to chemotherapy, but the majority of patients died from opportunist infections.

Acquired immunodeficiency syndrome (AIDS) in an economically disadvantaged population.

Forty patients with acquired immunodeficiency syndrome (AIDS), 70% of whom were intravenous drug abusers (IVDAs), were seen over a 20-month period (July 1, 1981, through Feb 28, 1983). Most of the patients came from two inner-city sections of New York City and from nearby correctional facilities. Eighty-five percent of the patients were black or Hispanic; only 15% were white. Unique features of AIDS in this mostly heterosexual population were the high incidence of opportunistic infections (90% of the patients), the low incidence of Kaposi's sarcoma (10%), and the high mortality rate (34% died during initial hospitalization, 74% after one year of follow-up). Tuberculosis occurred in 10% of cases, preceding other opportunistic infections by four to 24 months. We found that AIDS was a common disease among inpatient IVDAs, and in one of the participating hospitals, its incidence was similar to that of infective endocarditis. Acquired immunodeficiency syndrome should be considered as the underlying illness in all IVDAs with oral thrush, shortness of breath, pneumonia, or extra-pulmonary tuberculosis.