The antihypertensive effect of crude stevioside obtained from the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) on previously untreated mild hypertensive patients was examined. Patients with essential hypertension were submitted to a placebo phase for 4 weeks. The volunteers selected in this phase were randomly assigned to receive either capsules containing placebo during 24 weeks or crude stevioside 3.75 mg/kg/day (7 weeks), 7.5 mg/kg/day (11 weeks) and 15.0 mg/kg/day (6 weeks). All capsules were prescribed twice a daily (b.i.d.), i.e. before lunch and before dinner. After the placebo phase and after each dose of crude stevioside, body mass index, electrocardiogram and laboratory tests were performed. During the investigation blood pressure (BP) was measured biweekly and the remaining data were collected at the end of each stevioside dose step. All adverse events were prospectively recorded but no major adverse clinical effects were observed during the trial. Systolic and diastolic BP decreased (p < 0.05) during the treatment with crude stevioside, but a similar effect was observed in the placebo group. Therefore, crude stevioside up to 15.0 mg/kg/day did not show an antihypertensive effect. Moreover, the results suggest that oral crude stevioside is safe and supports the well-established tolerability during long term use as a sweetener in Brazil.

ALVES-DO-PRADO W, CORRADO AP, PRADO WA. Reversal by atropine of tetanic fade induced in cats by antinicotinic and anticholinesterase agents. Anesth Analg 1987;66:492-6. The tetanic fade induced by intraarterial adtninistratioiz of neostipiiie or by subparalyzing doses of d-tubocurarine or /zexariit~thoriiuiii zuas studied in cat anterior tibial muscle p r e p ra t io n s . The prior adm in is t ra t ion of atropine sign ificarztly reduced the time for recovery from the tetanic fade induced by the abozie nzenfioned drugs. A similar response zim seeti udzen atropine was adniinistered prior to neostig rnine adniinistration for reziersal of paralyziiig doses of d-tubocurarine. We interpret these results to slioul that presynaptic inuscarinic receptors participate in a negntizie feedback affecting acetylcholine release at the neiiroiniis~iilnr junction.

The antiulcer activity of the total extract and the fractions of Stryphnodendron adstringens was studied in rats and compared with that of cimetidine. Ulcers were induced in rats by means of three experimental models: acute stress, acidified‐ethanol and indomethacin. The total extract and the fractions were found to have significant antiulcer activity in the case of the acute stress and acidified‐ethanol models. These findings support the use of S. adstringens extracts in the treatment of gastric lesions. Copyright © 1999 John Wiley & Sons, Ltd.

The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.

1. Train-of-four fade (TOF(fade) ) is a clinically useful parameter to monitor the degree of block of neuromuscular transmission in curarized patients. Experimentally, TOF(fade) has been attributed to the blockade of facilitatory nicotinic receptors on motor nerve terminals. There is less information regarding the involvement of coexistent presynaptic receptors (e.g. muscarinic M(1) and M(2) , adenosine A(1) and A(2A) ) in the TOF(fade) produced by antinicotinic agents. 2. In the present study, we evaluated the TOF(fade) caused by antinicotinic neuromuscular relaxants (hexamethonium, d-tubocurarine, vecuronium and rocuronium) as the ratio of the muscle tension produced in the rat diaphragm by the fourth to the first stimulus (T(4) /T(1) ) of a train-of-four stimuli delivered to the phrenic nerve trunk at a frequency of 2 Hz. 3. All antinicotinic agents, except hexamethonium, decreased the amplitude of muscle tension during the first stimulus. Hexamethonium, (5.47 mmol/L), d-tubocurarine- (1.1 μmol/L), vecuronium (4.7 μmol/L)- and rocuronium (9.8 μmol/L)-induced TOF(fade) was attenuated by 10 nmol/L pirenzepine (an M(1) receptor antagonist), 1 μmol/L methoctramine (an M(2) receptor antagonist) and 2.5 nmol/L 1,3-dipropyl-8-cyclopentylxanthine (an A(1) receptor antagonist). Blockade of the A(2A) receptor with 10 nmol/L ZM241385 partially reversed the TOF(fade) induced by d-tubocurarine, vecuronium and rocuronium, but not that caused by the 'pure' neuronal nicotinic receptor antagonist hexamethonium, unless one increased the concentration of ZM241385 to 50 nmol/L. 4. The data indicate that presynaptic M(1) , M(2) , A(1) and A(2A) receptors play a role in neuromuscular TOF(fade) caused by antinicotinic neuromuscular relaxants. Such interplay depends on adenosine tonus and on the affinity of neuromuscular blocking agents for neuronal versus muscular nicotinic receptors.