Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor.

The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED50 values in the range 20-30 mg/kg/3 days. Both were also equipotent in suppression of PMN infiltration induced by PAF with ED50 values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis.

The developmental accumulation of gamma-glutamyl transferase in the pancreas of the rat.

The developmental accumulation of pancreatic exocrine secretory enzymes is well defined, but little is known of the development of other enzymes in the pancreas. This report focuses on the developmental accumulation of gamma-glutamyl transferase (GGT), a membrane-bound ectoenzyme whose specific activity in the pancreas is the second largest among rat organs. GGT activity is large in organs with active glutathione metabolism. Pancreatic GGT specific activity increased 100-fold from prenatal day 14 to birth, decreased 3-fold until about postnatal week 2, and then increased until the adult value was reached 4 weeks after birth. There was a 500-fold increase in specific activity from prenatal day 14 to the adult. The developmental accumulation pattern of GGT was very similar to that of the exocrine secretory enzyme amylase, which increased 1,300-fold from prenatal day 14 to birth, decreased 8-fold by postnatal week 1, and then increased to the adult level soon after week 4. The overall increase in amylase specific activity was 1,100-fold. The similar developmental accumulation patterns of GGT and amylase suggested that their accumulation might be regulated in a similar fashion. Although the thymidine analogue 5-bromodeoxyuridine inhibited the prenatal accumulation of amylase, as previously reported, it did not inhibit prenatal GGT accumulation. Therefore, the prenatal accumulation of GGT appears to be regulated differently than amylase. On the other hand, the postnatal levels of GGT appear to be controlled by glucocorticoids in a fashion similar to the previously reported control of amylase levels, since both enzymes could be induced to rise prematurely to adult levels by a series of three injections of the glucocorticoid dexamethasone beginning on days 7, 8, 9, 10, 11, or 12.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of neutrophil chemotaxis in methotrexate-treated rheumatoid arthritis patients.

Polymorphonuclear cell (PMN) chemotaxis was assessed using the in vitro under agarose assay in ten rheumatoid arthritis patients prior to and following a single 10-mg dose of methotrexate (MTX). PMNs obtained from patients after MTX showed a decreased chemotactic migration response to both zymosan activated serum (P less than 0.005) and N-formyl-L-methionyl-L-phenylalanine (P less than 0.01). In similar conditions, no significant difference in chemotactic migration could be detected in six rheumatoid arthritis patients not on MTX. In contrast to the in vivo effects of MTX, there was no inhibition of normal PMN chemotactic migration following a 30-min in vitro incubation of the cells with MTX (P less than 0.99).

The effect of low dose chronic intermittent parental methotrexate on delayed type hypersensitivity and acute inflammation in a mouse model.

We have shown that a regimen of low dose intermittent methotrexate (MTX), analogous to that used in the treatment of patients with rheumatoid arthritis, does have immunosuppressive effects on the induction of primary delayed type hypersensitivity in normal mice. This occurred even when the last MTX injection was 4 days before immunization. No effect was seen on established delayed type hypersensitivity or on inflammatory responses induced by carrageenan or the Arthus reaction.

Disease-modifying agents and immunosuppressive drugs in the elderly.

Disease-modifying and immunosuppressive therapies are required for elderly patients with rheumatic disorders. The evidence to date suggests that the criteria for choosing a particular drug is not vastly different from the choice in younger patients, and that the elderly have a similar response. More care is required in monitoring elderly patients on immunosuppressive drugs because of the potential for increased adverse reactions consequent on reduced functional capacity of major end organs. There is little data available to judge relative efficacy of these drugs in the elderly and with the 'greying' of the population these data should be sought after. With careful individual choice of drug and regular reassessment for effect and adverse drug reactions, many elderly patients with rheumatic diseases can obtain useful benefit from these agents.

Rapid progression of oxalosis-induced cardiomyopathy despite adequate haemodialysis.

Crystals of calcium oxalate (CaC2O4) were found at autopsy in the heart of a patient who, over a period of 11 months, appeared to receive adequate haemodialysis and yet died of rapidly progressive heart failure. Calcium oxalate crystals were not present in the kidneys which had been removed at the time of commencing haemodialysis. No secondary cause of oxalosis was evident. X-ray fluorescence analysis of the heart tissue revealed, as well as large amounts of calcium, excess strontium and markedly reduced amounts of potassium and rubidium.