R. Wilson

THE EFFECT OF ANTITHYROID DRUGS ON B AND T CELL ACTIVITY IN VITRO

This study examined the abilities of methimazole, propylthiouracil (PTU) and propranolol to exert an immunosuppressive effect in vitro. Incubation of peripheral blood lymphocytes (PBL) with propranolol showed the drug to have no effect on either B‐ or T‐cell activity. Methimazole or PTU at concentrations of ≥ 10−5M resulted in significantly lower amounts of IgG and IgM being released into the culture medium. Both drugs were also found to have a direct effect on T‐cell function as they caused the percentage of total and suppressor cells to increase towards normal levels. The three drugs were all found to have some free radical scavenging ability. These ranked PTU > methimazole > propranolol. These in‐vitro findings would suggest that both methimazole and PTU have some direct effect on the immune system. It would seem more likely however that these effects are mediated via interleukin 2 rather than by their ability to act as free radical scavengers.

THE ABILITY OF THE SERUM THYROTROPHIN RECEPTOR ANTIBODY (TRAb) INDEX AND HLA STATUS TO PREDICT LONG-TERM REMISSION OF THYROTOXICOSIS FOLLOWING MEDICAL THERAPY FOR GRAVEs' DISEASE

In agreement with previous authors we found patients with Graves disease to have an increased incidence of the DR 3 antigen. We could find no association, however, between the presence of the antigen and relapse after carbimazole treatment. A concordant HLA status and thyrotrophin receptor antibody (TRAb) index, obtained at either 6 or 12 months after the start of treatment could only predict cases of relapse and remission in a minority of patients making this of very limited clinical use. The TRAb index obtained at 12 months after the start of medical therapy could accurately predict cases of relapse and remission for the next 3 years in 24/30 patients studied.

The "in vitro" effects of lithium on the immune system.

This study has examined the in vitro effects of Lithium Carbonate on the immune system at low (10(-3), 10(-2)mM) and therapeutic (0.5-1.5 mM) concentrations. Lithium, in the presence of a range of mitogens, was found to increase the incorporation of 3H-thymidine into peripheral blood mononuclear (PBM) cells. At concentrations greater than 1 mM IL2 production was also enhanced. Lithium was also found to increase IgG and IgM production--an estimate of B cell function, the effects being greatest at concentrations within the therapeutic range. However at these levels Lithium inhibited cAMP production. Whether Lithium acts individually on these processes or whether one reaction is merely the result of another is unclear at present.

Clinical analysis in intact erythrocytes using 1H spin echo NMR

A new method of clinical analysis based on 1H spin echo NMR spectroscopy is presented. It is capable of providing information on six metabolites within viable erythrocytes, directly and without any preparative procedures prior to analysis except for cell separation and washing. Erythrocytes from patients with rheumatoid arthritis and Graves disease are compared with cells obtained from healthy volunteers. The NMR detectable species in the cytosol of the cells are glutathione, ergothioneine, choline, creatine, glycine, lactate and to a lesser extent alanine and valine. Significant differences are observed between the ergothioneine pools in the rheumatoid group (P less than 0.01) compared to the control group. The glutathione: di-glutathione ratio can be assessed from the ratio, g2 to g4, taken from different signals in the glutathione molecule. The total concentration of glutathione present is easily assessed qualitatively but is more difficult to quantitate.

Spin echo nuclear magnetic resonance studies on intact erythrocytes: changes in cellular metabolism as a consequence of carbimazole therapy

OBJECTIVE Because the exact mechanism of action of carbimazole is uncertain, nuclear magnetic resonance (NMR) spectroscopy was used to investigate cellular changes in erythrocytes from Graves patients following a course of carbimazole therapy.

Myocrisin-mediated oxidative stress

This study reports on the ability of myocrisin to mediate in the production and detoxification of oxidants (principally hydrogen peroxide) in the monocyte in-vivo and in-vitro. The hydrogen peroxide produced by the monocyte derived from rheumatoid arthritis patients being treated with myocrisin was found to be 14.9 +/- 1.6 nmoles/10(6) cells and is elevated above levels found in monocytes obtained from patients either being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (11.3 +/- 0.4 nmoles/10(6) cells; P < 0.01) or normal healthy volunteers (11.2 +/- 1.2 nmoles/10(6) cells; P < 0.01). A comparative study on glutathione (GSH) oxidation indicated that levels of monocyte GSH were elevated in myocrisin-treated patients (2.4 +/- 0.49 mmol/l) over normal healthy volunteers (0.83 +/- 0.18 mM; P < 0.01) and that levels of monocyte diglutathione (GSSG) were depressed (myocrisin, 0.97 +/- 0.41 micromol/l; normal, 5.71 +/- 0.73 micromol/l; P < 0.01). The non-inhibition of glutathione reductase and the inhibition of glutathione peroxidase by gold provides the link between these two observations. Thus, gold therapy would seem to elevate monocyte hydrogen peroxide, increase monocyte reduced glutathione and decrease plasma glutathione peroxidase activity. Subsequently, the data from this small group of patients (n = 10) provides an indication that, in-vivo, myocrisin contributes to an increase in oxidative stress.

Immunological changes in pregnancy-induced hypertension

Aspects of T and B cell function were studied in women with pregnancy-induced hypertension (PIH) and normotensive pregnant women by determining the proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by mitogens (PHA, ConA and PWM) and by determining IgG and IgM levels in the culture supernatant. The results showed that the proliferation of PBMC without mitogens was significantly increased in PIH women without proteinuria compared with normotensive pregnant women. In the presence of PHA, [3H]thymidine uptake in PBMC was statistically higher in PIH women both with and without proteinuria than that in normotensive pregnant women. ConA and PWM mitogen activities were not significantly different between PIH women and normotensive pregnant women. Compared with normotensive pregnant women, IgG production was significantly increased in PIH women with proteinuria but not in those without proteinuria. IgM production was not changed in PIH women. We concluded that immunologic responses in PIH women were increased rather than decreased. This increased immunologic activity is in accordance with some important changes seen in PIH, such as an increase in intracellular calcium, the presence of blood-borne mitogenic factor and a decrease in prostaglandin E series. These findings also support the hypothesis that PIH might result from the imbalance between fetal antigenic load and maternal production of immunologic blockade.

Studies of oxidative stress in cellular systems : the interaction of monocytes and erythrocytes

1H spin echo NMR spectroscopy is used to follow the interaction of intact and viable erythrocytes and monocytes obtained from different sources in mixed cultures. After a lag time (270 min) erythrocyte glutathione is observed to become more oxidised. This result is believed to occur as a consequence of monocyte activation generating hydrogen peroxide or hypochlorous acid, which is targeted at the erythrocyte. The red cell in turn employs its sulphydryl system as an anti‐oxidant defence.

Effects of Atenolol, Labetalol and Methyldopa on Endogenous Antioxidants In-vitro

The aim of this study was to investigate whether atenolol, labetalol and methyldopa, which are commonly used for the treatment of hypertension in pregnancy, can induce antioxidant activity.