The formation of procainamide hydroxylamine by rat and human liver microsomes.

A method is described, using HPLC and electrochemical detection, which permits the direct quantitation of procainamide hydroxylamine. Procainamide hydroxylamine was formed from procainamide by hepatic microsomes from both rat and human, with rat microsomes showing higher apparent formation rates. The apparent Km for formation of procainamide hydroxylamine was 0.

The in vitro effect of select classes of nonsteroidal antiinflammatory drugs on normal cartilage metabolism.

The in vitro effect of piroxicam, a newer nonsteroidal antiinflammatory drug (NSAID), on normal cartilage metabolism has been studied and response contrasted to indomethacin and sodium salicylate. Therapeutic levels of piroxicam has no effect on cartilage glycosaminoglycan (GAG), collagen or noncollagen protein synthesis by porcine weight bearing articular cartilage explants. Salicylate consistently suppressed GAG and protein synthesis, whereas indomethacin had no consistent effect on GAG production but suppressed protein synthesis.

Cartilage metabolism and anti-inflammatory drugs in osteoarthritis.

The issue of selecting nonsteroidal anti-inflammatory drugs (NSAIDs) for the management of osteoarthritis based upon their direct effect on normal cartilage metabolism and their ability to modulate mechanisms that disturb such metabolism is addressed. This article provides an overview of the anatomic and biochemical changes that occur in diseased synovial tissue and cartilage, and the pathophysiologic mechanisms presumed to function in the induction and perpetuation of cartilage failure. Studies using experimental animal models of osteoarthritis are reviewed to evaluate the natural history of the disease, as well as the direct effect of NSAIDs on anabolic and catabolic cartilage function.

Functional recovery of D1 dopamine receptor-mediated stimulation of rat striatal adenylate cyclase activity following irreversible receptor modification by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): evidence for spare receptors.

We report here the functional relationship between the time-dependent recovery of [3H]SCH 23390-labeled D1 dopamine receptors and the D1 receptor-mediated stimulation of rat striatal adenylate cyclase activity following irreversible receptor modification by in vivo administration of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. Initial decreases in receptor density (-93%) and receptor-mediated enzyme activity (-78%) were accomplished without concomitant changes in guanosine triphosphate or forskolin-stimulated enzyme activity. The percentage of maximal D1 receptor-mediated enzyme activity was significantly greater than that of D1 receptor density at all recovery times.

Field tests of the response of female Amblyomma variegatum (Acari:Ixodidae) to the synthetic aggregation-attachment pheromone and its components.

Fifty percent of an Amblyomma variegatum female population were able to find upwind-positioned targets containing the synthetic aggregation-attachment pheromone of this species or the pheromone component o-nitrophenol alone. The ticks were not attracted to the other components of the pheromone: methyl-salicylate and pelargonic acid. The mean time required for the ticks to reach a target at 1 m from the starting point was 3 min and 20 s.

Effects of chronic SCH23390 treatment on the biochemical and behavioral properties of D1 and D2 dopamine receptors: potentiated behavioral responses to a D2 dopamine agonist after selective D1 dopamine receptor upregulation.

Chronic treatment of rats with SCH23390 (0.5 mg/kg/day s.c.

Forskolin potentiates the stimulation of rat striatal adenylate cyclase mediated by D-1 dopamine receptors, guanine nucleotides, and sodium fluoride.

We report here that forskolin acts in a synergistic manner with dopaminergic agonists, guanine nucleotides, or sodium fluoride to potentiate the stimulation of rat striatal adenylate cyclase mediated by these reagents. In the presence of 100 microM GTP, 100 microM guanyl-5'-yl imidodiphosphate [Gpp(NH)p], or 10 mM NaF, there is a greater than additive increase in forskolin-stimulated enzyme activity as well as a concomitant decrease (two- to fourfold) in the EC50 value for forskolin stimulation of striatal enzyme activity. In the presence of various concentrations of forskolin (10 nM-100 microM), the stimulation of adenylate cyclase elicited by GTP, Gpp(NH)p, and NaF is potentiated 194-1,825%, 122-1,141%, and 208-938%, respectively, compared with the stimulation by these agents above basal activity in the absence of forskolin.

Guanine nucleotide regulation of agonist interactions at [3H]SCH23390-labeled D1 dopamine receptors in rat striatum.

We report here the regulation of agonist interactions with [3H]SCH23390-labeled D1 dopamine receptors in rat striatum. Scatchard analyses of [3H]SCH23390 saturation data revealed a single high affinity binding site (KD = 0.49 nM) with a Bmax of 64 pmol/g tissue.

Polynucleotide antibodies in connective tissue disease: viral markers or disease mediators?

Antibodies to polynucleotides are seen primarily in systemic lupus erythematosus (SLE), but also occur in a variety of other connective tissue diseases. We looked at the prevalence of antinucleotide antibodies (double- and single-stranded RNA and DNA [dRNA, sRNA, dDNA, and sDNA]) in the sera of patients with SLE (70), rheumatoid arthritis (RA) (31), juvenile rheumatoid arthritis (JRA) (68), osteoarthritis (12), and of 22 patients with a preceding viral illness. In comparison with sera from a control population, elevated mean antibody levels to sRNA were found in the sera of all the patients with connective tissue disease, as well as in the sera of patients with preceding RNA, but not DNA, viral infections.

D2 dopamine receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat striatum.

Forskolin markedly stimulates striatal adenylate cyclase activity in a concentration-dependent manner, and at 10(-4) M produces an approximate 40-fold increase in enzyme activity above basal levels. Dopamine (in the presence of 100 nM SCH 23390), bromocryptine and quinpirole (LY 171555) significantly inhibit both basal and forskolin-stimulated adenylate cyclase activity. There is a significant increase in the absolute but not in the percent inhibition of enzyme activity by dopaminergic agonists as a function of forskolin concentration.

Familial alterations of immunoregulation in systemic lupus erythematosus.

To better define the relationship between suppressor cell function and number and disease expression, the immunoregulatory profiles of 12 probands with systemic lupus erythematosus (SLE) and 34 of their asymptomatic family members were studied, using concanavalin A induced suppressor cells for functional analysis. SLE family members as a whole showed no impairment of mean suppressor levels, although 7 of 34 had altered suppression of DNA synthesis and 5 of 34 had altered suppression of IgG synthesis. Ratios of OKT4/T8 T cell subsets showed no difference between the study population, although 3 SLE family members had an increased ratio (greater than 2 SD) relative to controls.

Skin effects of occupational kneeling.

To evaluate chronic knee trauma associated with kneeling, we conducted a cross-sectional questionnaire survey among floorlayers and tilelayers, two trades that require kneeling. Bricklayers and millwrights were studied for comparison. Approximately 28% of the 432 questionnaire respondents volunteered for a subsequent medical examination.

Nonsteroidal anti-inflammatory drugs and modulation of cartilaginous changes in osteoarthritis and rheumatoid arthritis. Clinical implications.

Nonsteroidal anti-inflammatory drugs have a potential for modifying the complex pathophysiologic events leading to cartilage destruction in various forms of arthritis. Following an evaluation of basic mechanisms in the pathogenesis of cartilaginous destructive lesions, the effects of nonsteroidal anti-inflammatory drugs on normal chondrocyte metabolism are discussed. Their capacity to modulate cartilage and bone lesions in experimental forms of arthritis is addressed, as is the manner in which they may modify the pathophysiology of cartilage destruction in human forms of arthritis.