Extracellular adenosine,formed during low level NMDA receptor activation,provides an inhibitory threshold against further NMDA receptor-midiated neurotransmission in the cortex

In the cortex only a few of the available NMDA receptors must be activated to evoke maximal release of adenosine. In fact, maximal adenosine release occurs at 30 μM NMDA, a concentration at which noradrenaline release is only 20% maximal. NMDA-evoked noradrenaline release appears to require the generation of propagated action potentials, while adenosine release does not. Noncompetitive block of NMDA-evoked release of adenosine, but not noradrenaline, can be overcome by increasing NMDA concentrations. The above findings are consistent with the possibility that there are spare receptors for NMDA-evoked adenosine release, but not for nor-adrenaline release. These spare receptors are not due to elevated levels of glycine in the vicinity of those NMDA receptors mediating adenosine release. Functionally, it appears that low level NMDA receptor activation provides a purinergic inhibitory threshold against higher level NMDA receptor mediated processes. This could provide inhibitory tone and selectivity for critical functions, such as learning, memory, and synaptic plasticity in the cortex. © 1993 Wiley-Liss, Inc.     

Fatal occupational injuries in the United States, 1980 through 1985

The National Traumatic Occupational Fatality surveillance project was designed to gather demographic, employment, and injury information from death certificates for all deaths due to injuries at work in the United States. Approximately 7000 workers have died each year during the 6-year period from 1980 through 1985: 94% were men, and 6% were women. Unintentional injuries caused the deaths of 83% of the men and 50% of the women. Eleven percent of the men and 39% of the women died from homicide. While the greatest number of deaths occurred in the group aged 20 through 34 years, fatality rates were highest among those aged 70 years and older. Expressed as deaths per 100,000 workers, annual fatality rates for black workers (7.7) were slightly higher than for white workers (6.5). The four industrial groups with the highest fatality rates were mining (31.9); transportation, communication, and public utilities (25.4); construction (24.0); and agriculture, forestry, and fishing (20.7). From 1980 through 1985 the annual traumatic occupational fatality rate fell 23%.     

Correlation between fall in blood pressure and in vivo amine release after alpha-methylDOPA

Blood pressure (BP), hypothalamic tissue concentrations and the in vivo overflow of endogenous and alpha-methylated catecholamines were measured in urethane anaesthetised rats after alpha-methylDOPA (mDOPA) administration (200 mg/kg i.p.). Four hours after mDOPA, BP fell to its lowest value, 60% of control, and slowly returned towards control levels by 24 h. This was closely correlated with the evoked overflow of alpha-methylnoradrenaline (mNA, r = 0.9) and noradrenaline (NA, r = 0.7) but not dopamine (DA) or alpha-methyldopamine (mDA). However, the tissue content of mNA rose much more gradually and was not maximal until after 12 h while mDA content followed the development of the hypotension. The results provide direct evidence for a false transmitter role for mNA in the brain, and suggest that the release of newly synthesised mNA is responsible for the hypotensive effect of mDOPA. Differences in the time course of overflow and storage of NA and mNA suggest the presence of separate transmitter storage and releasable pools.     

Piretanide in the treatment of essential hypertension. A double-blind comparison versus placebo

In a randomized, double-blind parallel group study the 24-hour hypotensive effect of piretanide and its influence on biochemical variables were compared with those of placebo in patients with mild to moderate essential hypertension. Sixty patients entered the study, all of whom met the inclusion criteria (RRdiast between 95 and 120 mmHg). There was no drop-out during the study, so that the results of all 60 patients were statistically analysed. Piretanide produced a significant reduction of both systolic and diastolic blood pressure over 24 hours which was evident at four weeks and was maintained and further enhanced over the ensuing trial period. A mean maximal fall (at 12 weeks) of 10.7% (BPdiast supine) was observed. Placebo tablets did not produce any clinically relevant changes in systolic blood pressure, whereas a slight decrease was seen in diastolic blood pressure. This blood pressure reduction was significantly less in the placebo group than in the piretanide group at the end of the study (weeks 10 and 12). Dose doubling was needed in 13 of the 30 patients in the piretanide group, whereas as many as 20 out of 30 patients needed dose doubling in the placebo group. Pulse rate did not change relevantly during the trial in either group. A slight reduction in body weight was observed in the piretanide group. The mean values of serum potassium and sodium showed a slight decrease but remained within the normal range during the study period. A small increase in serum phosphorus was noted. None of these changes required any specific measures.(ABSTRACT TRUNCATED AT 250 WORDS)