David L. Larson

TENIDAP, A STRUCTURALLY NOVEL DRUG FOR THE TREATMENT OF ARTHRITIS : ANTIINFLAMMATORY AND ANALGESIC PROPERTIES

Tenidap is a new anti-rheumatic agent which has clinical properties characteristic of a disease modifying drug combined with acute antiinflammatory and analgesic activity. This paper details tenidaps cyclooxygenase (COX) inhibitory activity and the resulting pharmacological properties in experimental animals. Tenidap inhibited calcium ionophore-stimulated prostaglandin D2 synthesis by rat basophilic leukemia cells (COX-1) with an IC50 of 20 nM. In two different in vitro human test systems, tenidap inhibited COX-1 activity more potently than COX-2, although the relative potency ratio (COX-1/COX-2) differed markedly between the two systems. Tenidap inhibited the COX pathway when added to human blood in vitro (IC50, 7.8 μM) and when administered orally to monkeys, rats and dogs (at 5, 2.5 and 10 mg/kg p.o., respectively) and COX activity measured ex vivo in blood collected 2 to 4 hours post dose. After oral administration to rats, tenidap inhibited carrageenan-induced paw edema with an ED50 of 14 mg/kg and inhibited the glucocorticoid-resistant UV erythema in guinea pigs with an ED50 of 1.4 mg/kg. It retained antiinflammatory activity in adrenalectomized rats indicating that this property is independent of adrenal stimulation. Oral administration of tenidap inhibited the development of adjuvant-induced polyarthritis in the rat and exhibited antinociceptive activity in the murine phenylbenzoquinone and rat acetic acid abdominal constriction tests. These data indicate that tenidap is an effective antiinflammatory and analgesic agent in animal models. These cyclooxygenase-dependent pharmacologic activities do not explain tenidaps disease modifying anti-arthritic properties but add a useful symptom modifying component to its clinical profile.

An analysis of piroxicam in rodent models of arthritis.

Piroxicam, a potent, long acting non-steroidal anti-inflammatory drug, was tested in several rodent models of arthritis to assess further the possible mechanisms underlying its anti-inflammatory action. Piroxicam inhibited rat adjuvant disease and its associated manifestations, which include erosion of bone and cartilage (as evidenced by X-ray examination), soft tissue swelling and disease-induced weight loss. Piroxicam also inhibited the edema, the total leukocyte infiltration and the mononuclear cell infiltration into the carrageenan-injected pleural cavity of the rat. The possible relationship of these effects to the clinical activity of piroxicam is discussed.

The topical anti-inflammatory effects of piroxicam in rodents.

Piroxicam is a structurally novel, long-acting anti-inflammatory drug with potent activity following oral administration in animal models of inflammation and in human inflammatory diseases. The present studies, performed in rats, demonstrate that topically applied piroxicam is a potent inhibitor of inflammation induced by either carrageenin or complete Freunds adjuvant. Comparable potencies (ED50 approximately 1–5 mg/kg) were obtained for topically and orally administered piroxicam in these models of inflammation. The potency of topical piroxicam exceeds that of topically applied bufexamac or phenylbutazone in the rat adjuvant arthritis model.

Biochemical and morphological studies of Simian sarcoma virus, type 1

Abstract A productive infection has been established in a primary human-embryo fibroblastic cell line (HE) by Simian Sarcoma Virus, Type 1 (SSV-1). The C-type virus particles observed in the HE and marmoset lung cells are similar in morphology. Rate zonal centrifugation and acrylamide-agarose gel electrophoretic analysis of radioactively labeled SSV-1 ribonucleic acid reveal a 60–70-S component which is heat sensitive, as well as 28-S, 18-S, and 4–10-S components, all of which are hydrolyzed by alkali. Studies employing the simultaneous detection assay for viral enzyme and 60–70-S RNA show that the virus has biochemical properties similar to other oncorna viruses.

AUTOMATED INFORMATION DELIVERY IN A PHARMACEUTICAL COMPANY

The computer system described in this article automates the process to deliver on-line information daily. On-line data (for this study we accessed the Scrip daily update file available through Data-star [Data-Star, Plaza Suite, 114 Jermyn Street, London, UK, SW1Y 6HJ.]) is automatically retrieved, downloaded onto a personal Computer, and uploaded to a VAX computer with a software communication package PROCOMM PLUS (PROCOMM PLUS, Datastorm Technologies, Inc., Columbia, MO.). The information that was then transferred to a database system, System 1032, (System 1032, CompuServe, Data Technologies, Cambridge, MA.) can be accessed and managed easily with a customized menu-driven system. Not only has this automated system saved us a significant amount of time as information providers, but it also allows users to access and utilize important information as soon as it becomes available.

The endogenous reverse transcriptase activity of gibbon ape lymphoma virus: Characterization of the DNA product

The DNA product of the endogenous reverse transcriptase reaction of Gibbon ape lymphoma virus has been analyzed and characterized. Data show that in simultaneous detection assays in which the type and/or concentration of divalent cation is varied the best yield of rapidly-sedimenting DNA was obtained from reactions containing 1.5 mM Mn2+. This yield is ten-fold better than the yield observed at the optimal Mg2+ concentration (5.0mM). Evidence is presented to show that DNA synthesized at the optimal concentration of either of these cations consists of large pieces varying in size from 4 to 12S. This DNA hybridizes efficiently to homologous viral RNA (greater than 60 percent annealing) and protects at least two-thirds of GALV 70S [32P]RNA from ribonuclease digestion. The hybrids formed with homologous viral RNA are stable as evidenced by their thermal elution patterns from hydroxylapatite columns. In contrast, DNA synthesized in reactions in which the concentration of Mn2+ or Mg2+ was greater than optimal was predominantly 4S or smaller in size and displayed a low level of hybridization (less than 10 percent) to homologous viral RNA.