The in vitro metabolism of D-lysergic acid diethylamide (LSD) by human liver microsomes was investigated. Tandem mass spectrometric techniques, using precursor and neutral loss scans, were employed in the initial search for drug metabolites. The determination of LSD human liver in vitro metabolites was performed by high-performance liquid chromatography and capillary electrophoresis coupled with tandem mass spectrometry. Two new in vitro metabolites, lysergic acid ethylamide (LAE) and 2-oxo-LSD, were positively identified; their structures were established by comparing with reference standards. Several other possible in vitro metabolites detected were suggested to be mono- and trioxylated metabolites of LSD. The major metabolic route of LSD by human liver microsomes is deethylation. Some results with LSD-positive human urine are presented. Among the LSD-related compounds detected in human urine specimens, iso-LSD was present at the highest concentration, followed by nor-LSD and isonor-LSD. Low concentrations of LAE and iso-LAE were also found in these urine specimens.

Chromatography, Liquid↗

PubMedDate not supplied

Progression to AIDS: the effects of stress, depressive symptoms, and social support.

OBJECTIVE: We examined the effects of stress, depressive symptoms, and social support on the progression of HIV infection. METHODS: Eighty-two HIV-infected gay men without symptoms or AIDS at baseline were followed up every 6 months for up to 5.5 years. Men were recruited from rural and urban areas in North Carolina as part of the Coping in Health and Illness Project. Disease progression was defined using criteria for AIDS (CD4+ lymphocyte count of <200/microl and/or an AIDS-indicator condition). RESULTS: We used Cox regression models with time-dependent covariates, adjusting for age, education, race, baseline CD4+ count, tobacco use, and number of antiretroviral medications. Faster progression to AIDS was associated with more cumulative stressful life events (p = .002), more cumulative depressive symptoms (p = .008), and less cumulative social support (p = .0002). When all three variables were analyzed together, stress and social support remained significant in the model. At 5.5 years, the probability of getting AIDS was about two to three times as high among those above the median on stress or below the median on social support compared with those below the median on stress or above the median on support, respectively. CONCLUSIONS: These data are among the first to demonstrate that more stress and less social support may accelerate the course of HIV disease progression. Additional study will be necessary to elucidate the mechanisms that underlie these relationships and to determine whether interventions that address stress and social support can alter the course of HIV infection.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Treatment of carbon tetrachloride and phenobarbital-induced chronic liver failure with intrasplenic hepatocyte transplantation.

Hepatocyte transplantation (HTx) has been shown to improve the survival of laboratory animals with experimentally induced acute liver failure and to ameliorate the physiologic abnormalities associated with liver-based metabolic deficiencies. However, the role of HTx in the treatment of liver cirrhosis (LC) has not been adequately studied. In order to address this issue, HTx was performed in rats following induction of stable LC using phenobarbital (PhB) and carbon tetrachloride (CCl4). Intrasplenic transplantation of 50 x 10(6) primary hepatocytes could significantly improve liver functions and prolong the survival of rats with irreversible, decompensated LC.

Animals↗

PubMedDate not supplied

Immunohistochemical detection of occult metastases in paraaortic lymph nodes in advanced gastric cancer.

Some Japanese surgeons have examined the utility of super-extended paraaortic lymphadenectomy (PAL) as part of the surgical treatment for advanced gastric cancer. However, therapeutic value of this PAL remains controvertial. The purpose of this study was to evaluate appropriate candidates who might benefit from PAL by the immunostaining with cytokeratin (CK) of the macroscopically intact paraaortic nodes. A total of 525 paraaortic nodes from 35 patients was serially sectioned and stained with hematoxylin-eosin (H&E) and CK staining. A total of 17 nodes (3.2%) from 7 patients (20.0%), among 525 macroscopically intact paraaortic nodes, was determined to be immunopositive for CK. In 4 patients, 8 H&E-positive nodes with metastases were all immunopositive and, in addition, 4 H&E-negative nodes were also immunopositive. Furthermore, 3 patients with H&E-negative nodes had five immunopositive nodes. Immunostaining with CK was useful for detection of occult metastases. Survival was prolonged in 3 of these 7 patients. The incidence of CK-positive nodes was significantly higher in patients with gross type of 3 or 4 gastric cancer and in patients with H&E-detected nodal metastasis within group 3 (N3) nodes. It seems that such patients would benefit from prophylactic PAL.

Aged↗

PubMedDate not supplied

Characterizing human colorectal carcinomas by proteolytic profile.

Clinicopathologic staging of colorectal cancers cannot always predict aggressiveness of prognosis for a particular patient. We have used activity assays for cysteine proteinases, cathepsins B, L and H (CB, CL and CH) and matrix metalloproteinases, MMP-2 and MMP-9, to identify several distinctive, reproducible proteolytic profiles in a large set of colorectal carcinomas. We observed that individual proteinases demonstrated specific and distinct levels of activity at different cancer stages, possible reflecting non-random steps in a proteolytic cascade related to tumor development. We also observed that individual colon cancers fell into relatively few categories when characterized for the combined expression of three proteinases: CB, CL and MMP-9. Four proteolytic profiles, designated "Early", "Middle", "Late", and "High", could be used to define almost 80% of the colorectal carcinomas analyzed. Such profiles, based on the expression of several proteinases in a given tumor, provided information independent of clinical stage and may identify crucial variations in tumor behavior.

Biomarkers, Tumor↗