Effect of metallothionein on tolerance of nitroglycerin in rats.

AIM: To assess whether metallothionein (Met) could improve the nitroglycerin tolerance in vivo. METHODS: Nitrate tolerance was induced by 2-d treatment of nitroglycerin (Nit) patch (0.05 mg.h-1). Endogenous Met production was induced by pretreatment of ZnCl2 and coadministration of intravenous Met (15 mg.kg-1.d-1) 2 d with Nit in tolerant rats. The induction of Met production was confirmed by the assay of liver and plasma Met levels. RESULTS: ZnCl2 induced large amount of endogenous Met production in liver and plasma in Nit + ZnCl2 group than that in control group, (89 +/- 4) micrograms/g tissue vs (11.0 +/- 2.4) micrograms/g tissue in liver, P < 0.01, and in plasma (85 +/- 6) micrograms.L-1 vs (71 +/- 6) micrograms.L-1, P < 0.01. There was no significant difference in plasma Met levels in Nit and control groups [(75 +/- 6) micrograms.L-1 vs (71 +/- 6) micrograms.L-1, P > 0.05]. The endogenous Met production enhanced the hypotensive response in Nit + ZnCl2 group [(15.7 +/- 0.8) kPa vs (11.5 +/- 0.6) kPa, n = 6, P < 0.05]. The maximal vessel relaxation induced by sodium nitroprusside (SNP) was the same in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response to SNP) was found in tolerant group [(42 +/- 9) nmol.L-1, P < 0.01]. CONCLUSION: Exogenous Met or induction of endogenous Met production antagonize the development of Nit tolerance.

Postnatal hypothermia and cold stress among newborn infants in Nepal monitored by continuous ambulatory recording.

AIMS: To describe the pattern of hypothermia and cold stress after delivery among a normal neonatal population in Nepal; to provide practical advice for improving thermal care in a resource limited maternity hospital. METHODS: The principal government funded maternity hospital in Kathmandu, Nepal, with an annual delivery rate of 15,000 (constituting 40% of all Kathmandu Valley deliveries), severe resource limitations (annual budget Pounds 250,000), and a cold winter climate provided the setting. Thirty five healthy term neonates not requiring special care were enrolled for study within 90 minutes of birth. Continuous ambulatory temperature monitoring, using microthermistor skin probes for forehead and axilla, a flexible rectal probe, and a black ball probe placed next to the infant for ambient temperature, was carried out. All probes were connected to a compact battery powered Squirrel Memory Logger, giving a temperature reading to 0.2 degree C at five minute intervals for 24 hours. Severity and duration of hypothermia, using cutoff values of core temperature less than 36 degrees C, 34 degrees C, and 32 degrees C; and cold stress, using cutoff values of skin-core (forehead-axilla) temperature difference greater than 3 degrees C and 4 degrees C were the main outcome measures. RESULTS: Twenty four hour mean ambient temperatures were generally lower than the WHO recommended level of 25 degrees C (median 22.3 degrees C, range 15.1-27.5 degrees C). Postnatal hypothermia was prolonged, with axillary core temperatures only reaching 36 degrees C after a mean of 6.4 hours (range 0-21.1; SD 4.6). There was persistent and increasing cold stress over the first 24 hours with the core-skin (axillary-forehead) temperature gap exceeding 3 degrees C for more than half of the first 24 hours. CONCLUSIONS: Continuous ambulatory recording identifies weak links in the "warm chain" for neonates. The severity and duration of thermal problems was greater than expected even in a hospital setting where some of the WHO recommendations had already been implemented.