Evaluation of Tenidap (CP-66,248) on human neutrophil arachidonic acid metabolism, chemotactic potential and clinical efficacy in the treatment of rheumatoid arthritis

Ten patients with rheumatoid arthritis (RA) were evaluated in a placebo-controlled, double-blind study examining the clinical efficacy of a novel nonsteroidal anti-inflammatory agent: Tenidap (CP-66,248). RA patients receiving active drug therapy (n = 6) demonstrated clinically significant improvements in observer assessment of pain (p less than 0.025), painful joint count (p less than 0.010), and overall clinical assessment as based on a modified rheumatoid activity index, MRAI (p less than 0.025). In parallel laboratory assays, Tenidap was found to exhibit a significant in vitro dose-dependent inhibition of ionophore-stimulated neutrophil production of the 5-lipoxygenase product: [3H]leukotriene B4 (LTB4). Although more importantly, Tenidap was also found to exhibit an in vitro dose-dependent inhibition (IC50 20 microM) of the ionophore-stimulated release (deacylation) of the precursor [3H]arachidonic acid (AA) from membrane phospholipids. In further studies, Tenidap did not have any effect on fMLP-induced neutrophil chemotactic response. These results suggest that one of the possible mechanisms for the clinical effectiveness of this agent, may be through its effect at inhibiting the release of free AA from membrane phospholipids and therefore limiting its further metabolism into certain biologically-active inflammatory lipids.     

Milk consumption in older Americans.

OBJECTIVES: The purpose of this study was to identify individual characteristics associated with types and frequency of milk consumption in older American adults. METHODS: A national probability-based sample (response rate = 91%) completed a telephone survey. Generalized logit and cumulative logit analyses were used to identify predictors of and barriers to fluid milk consumption in 494 elderly people. RESULTS: The likelihood of drinking skim or 1% milk rather than whole milk increased with nutrition knowledge, income, trying to reduce cholesterol intake, and being female (P < .05). Frequency of milk consumption was higher with nutrition knowledge, frequency of milk consumption during adolescence, and following a diabetic diet but was lower with milk intolerance. CONCLUSIONS: The present results could be used to develop intervention strategies for improving milk consumption rates among older adults. These strategies might focus on increasing elderly people's awareness of milk intolerance and lactose-reduced milk products and their concern about cholesterol. The relationship between current and adolescent milk consumption suggests that intervention strategies should begin early in life.     

Is schizophrenia genetically transmitted?

Clinicians and researchers alike have questioned and studied the origin of schizophrenia for decades. Since the early 1900s, a genetic hypothesis has been suggested. This article reviews studies on a possible genetic cause of schizophrenia by use of various methods of comparison: twins, adoption, family history, family studies, and studies of biologic markers. Most researchers conclude that schizophrenia is likely caused by a genetic predisposition coupled with environmental influences.     

Dietary fat intake and plasma lipid levels in adolescents.

The relationship between dietary fat intake and fasting plasma lipid levels was assessed in 35 female and 19 male adolescents recruited from two local education authority schools in Norwich, UK. Dietary intakes were assessed using a 7-day weighed dietary record method, coupled with the collection of duplicate diets. Fat and energy intakes calculated using food composition tables were compared with values obtained by direct analysis of duplicate diets. Fasting plasma lipid levels (total, HDL and LDL cholesterol and triglycerides) were measured and compared with total dietary lipids and fatty acid intakes. The average proportion of energy consumed as fat was higher than is currently considered desirable but lower than previous studies have reported for adults. Mean serum total cholesterol values were 4.2 (SEM 0.1) mmol for females and 4.5 (SEM 0.2) mmol for males; this difference was not statistically significant. In male subjects the dietary fatty acid profiles were significantly correlated with several parameters of plasma lipid status which are thought to be risk factors for coronary heart disease, and in particular with the ratio of total:HDL cholesterol.     

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.