9ZR1 Methylenedioxymethamphetamine (MDMA,`ecstasy'), widely used as a recreational drug, can produce hyponatraemia. The possibility that this could result from stimulation of vasopressin by MDMA or one of its metabolites has been investigated in vitro. 2 Release of both oxytocin and vasopressin from isolated hypothalami obtained from male Wistar rats was determined under basal conditions and following potassium (40 mM) stimulation. The results were compared with those obtained for basal and stimulated release in the presence of MDMA or metabolites in the dose range 1 mM to 100 pM (n=5 ± 8) using Student's t-test with Dunnett's correction for multiple comparisons. 3 All compounds tested a ected neurohypophysial hormone release, HMMA (4-hydroxy-3-methoxymethamphetamine) and DHA (3,4-dihydroxyamphetamine) being more active than MDMA, and DHMA (3,4-dihydroxymethamphetamine) being the least active. The e ect on vasopressin release was greater than that on oxytocin. In the presence of HMMA the ratio test:control for basal release increased for vasopressin from 1.1+0.16 to 2.7+0.44 (s.e.m., P50.05) at 10 nM and for oxytocin from 1.0+0.05 to 1.6+0.12 in the same hypothalami. For MDMA the ratio increased to 1.5+0.27 for vasopressin and to 1.28+0.04 for oxytocin for 10 nM. 4 MDMA and its metabolites can stimulate both oxytocin and vasopressin release in vitro, the response being dose dependent for each drug with HMMA being the most potent.

3,4‐Methylenedioxymethamphetamine (MDMA) has been reported to cause hyponatraemia, which appears to result from inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). After administration of a low dose of (R,S)‐MDMA (40 mg) to eight healthy drug‐free male volunteers, concentrations of AVP in plasma increased significantly at 1, 2, and 4 hours. Although no relation between plasma MDMA and AVP was found on an examination of the entire data set over the 24‐hour study period, a statistically significant negative correlation was observed at 1 hour. As this occurred at a time when both AVP and MDMA concentrations were rising, it was postulated that a metabolite, or metabolites, could primarily be responsible for the increase in AVP. To test this hypothesis we examined the effect of MDMA and five of its metabolites, in the dose range 0.1‐1,000 nM, on AVP release from the isolated rat hypothalamus. All compounds tested were found to increase AVP release (using 10 nM and 1,000 nM concentrations), with 4‐hydroxy‐3‐methoxymethamphetamine (HMMA), the major metabolite of MDMA, being the most potent, and 3,4‐dihydroxymethamphetamine (DHMA) the least potent. Each compound (1,000 nM), with the exception of DHMA, also enhanced the response to 40‐mM potassium stimulation. Our findings confirm that metabolites of MDMA, in addition to the parent drug, contribute to AVP secretion in vitro. Further work will demonstrate whether this is also true in vivo.

Drug resistant tuberculosis (TB) cases are primarily driven by transmission, however, treatment failure and acquisition of drug resistance are still significant issues in drug sensitive TB cases.Study of gene expression in Mycobacterium tuberculosis (Mtb) isolated from poor outcome patients may offer clues towards prediction of treatment response. In the current study, expression of five non-drug target genes (ppsD, embC, Rv1457c, Rv1687c and recB) previously identified to be associated with drug resistance was studied in clinical isolates from patients with different treatment outcomes to examine its correlation to treatment response and acquisition of drug resistance in Mtb. Our results show that expression of ppsD, a gene involved in synthesis of cell wall lipid PDIM, was significantly increased in patients who developed drug resistance during treatment and patients who were drug resistant at diagnosis. On the other hand in longitudinal isolates collected during treatment, ppsD expression decreased consistently in patients who responded to treatment and became culture negative, while it increased in patients who did not respond to treatment as indicated by their culture positive status towards the end of treatment.These results demonstrate that ppsD expression reflects treatment response in TB patients and hence can be potentially used as a marker for predicting treatment response. Additional longitudinal studies with a larger cohort of patients are required to establish application of ppsD expression as a marker of treatment response.

Introduction Diagnosis of tuberculosis (TB) ideally involves culture and sensitivity of the organism but in low income countries this is not practised routinely. The World Health Organisation estimates that substandard detection occurs in 40% of patients globally, with many diagnosed on clinical suspicion or response to medication. TB produces a strong antibody response suitable for simple, inexpensive and rapid serodiagnostic assays. Ongoing evaluation of a new point of care rapid serological test based on lateral flow immunochromatography (TB-ST Rapid Test, Lionex, Germany) has shown 100% specificity, with no false positive tests in normal controls and latently infected patients, but sensitivity of 36%, with false negatives in culture proven TB. Aim Using this test in a resource poor setting to investigate whether cases of active TB may be being missed by current diagnostic methods. Methods 498 patients in chest and HIV clinics in two rural Kenyan hospitals were investigated with the TB-ST Rapid Test and a scored questionnaire to determine symptoms and risk of TB. Results were compared with clinical diagnoses made, usually based on symptoms alone. Chest radiographs were performed in only 111 and sputum smears in 75.Results 127/498 patients were HIV positive. Of these, only 59(46%) had a clinical diagnosis of TB, whereas 87(68.5%) had significant TB symptoms and/or risk factors, and 82(64.6%) tested TB-ST positive (p<0.001). Therefore clinical diagnosis accounted for significantly fewer diagnoses of active TB than suggested by either symptom and risk score or TB-ST rapid results in the HIV+ population. Of the 375 HIVÀ patients, 73 (19.7%) had a clinical diagnosis of TB, 46 (12.3%) scored positive for TB on the questionnaire, and 149 (40.2%) were TB-ST+ (p<0.001). Abstract P165 Conclusions Many more patients had positive TB-ST and risk and symptom scores than were being diagnosed with active TB, suggesting that TB may not always be being diagnosed or treated. Sputum smears were in greater agreement with the TB-ST in HIVÀ but not HIV+ patients, in whom there were considerably fewer positive smears than TB-ST results.