No abstract

These findings suggest that there is abnormal autonomic influence on the heart in patients without coronary artery disease at risk of sudden cardiac death. Hourly analysis of heart rate variability throughout the 24 hour period may provide additional information important in the identification of high risk patients.

Peroxisome proliferator-activated receptors alpha (PPARα) is a therapy target in atherosclerosis and cardiovascular diseases. However, anti-inflammatory effects of PPARα in intracerebral hemorrhage (ICH) remain unknown. We investigated the anti-inflammatory effects of fenofibrate, a ligand of PPARα, in ICH rat model. We found that engagement of fenofibrate increased nissl body and astrocytes, and reduced the neuronal damage, which was observed in paraffin section of ICH rat brain. Fenofibrate also promoted the proliferation of astrocytes that were isolated from adult rat brain. Fenofibrate significantly upregulated heme oxygenase 1 (HO-1) at protein and mRNA levels in human glioblastoma LN-18 cells and rat brain astrocytes respectively, but nuclear factor kappalight- chain-enhancer of activated B cells (NFκB) was downregulated after fenofibrate treatment. Results showed that fenofibrate-induced upregulation of HO-1 expression were inhibited after LN-18 cells were transfected with 50nM small interfering RNA (siRNAs) for 48 hours to knockdown PPARα. Further studies in rat astrocytes confirmed the rescue effects of PPARα silence against fenofibrate induced upregulation of HO-1 expression. Our data indicated that fenofibrate benefits neuronal protection through increasing HO-1 expression level and decreasing NFκB expression in PPARα-dependent manner. In conclusion, PPARα and HO-1 may function as significant targets to protect the brain during ICH.

A simple method has been described by which the action of drugs on the stressinduced block in milk ejection can be investigated on lactating guinea-pigs. Reserpine, meprobamate and chlorpromazine when administered to the lactating mother at various periods before suckling reduced the block in milk ejection caused by the stress. Dibenamine and dichloroisoprenaline did not affect in any way the stressinduced block. It is suggested that the stress-induced block in milk ejection is probably a nervous block and not mediated through adrenaline.It has been known for a long time that fright or nervousness inhibits proper feeding of infants and milking in lactating animals. Ely & Peterson (1941) demonstrated marked inhibition of milk ejection in frightened cows, and Newton & Newton (1948) described inhibition of milk ejection caused by fear, embarrassment and anger in a lactating subject. It has been demonstrated that intravenous administration of adrenaline or stimulation of the sympathetic areas of the hypothalamus blocks the milk-ejection reflex (Cross, 1953(Cross, , 1954. Cross (1955) has produced the stress-induced block of milk ejection in lactating rabbits and studied the mechanism of this block. The present concept appears to be that the adrenaline released in stress may block milk ejection by its vasoconstrictor action on the mammary myoepithelium. This peripheral action of adrenaline has been well demonstrated (Cross, 1953). It is, however, possible that the adrenaline released in stress may prevent the release of oxytocin and also that there may be other factors concerned in the psychological block of milk ejection. The effect of drugs on the stress-induced block of milk ejection does not appear to have been investigated in experimental animals. In this investigation the effect of some of the tranquillizers and two adrenergic nerve blocking drugs on the milk-ejection reflex in stress has been studied on the lactating guinea-pig. METHODSGuinea-pigs were bred in the animal house and the litter of each guinea-pig reduced to two for purposes of the experiment. Experiments were carried out from the third to the tenth day after birth of the litter. The two young guinea-pigs were separated overnight from the mother and weighed next morning before suckling. They were placed with the mother for 5 min, at the end of which period they were weighed again. When the weight gain of the * Post-doctoral Fellow of the National Research Council of Canada.

The delay of diuresis caused by reserpine in hydrated rats was not consistently prevented by prior administration of dibenamine or a potent anti-5-hydroxytryptamine substance (Methysergide), to the rats at the time of hydration. Carotid blood from rats under ethanol anaesthesia did not contain detectable antidiuretic activity. After administration of an intravenous dose of reserpine (50 μg/100 g) carotid blood collected at the time of maximum antidiuresis contained a detectable amount of antidiuretic activity which, in four experiments out of five, was destroyed by sodium thioglycollate. This, together with the finding that reserpine prolongs the time to the maximum rate of excretion of urine in hydrated rats, suggests that reserpine releases antidiuretic hormone from the neurohypophysis.

The delay of diuresis caused by reserpine in hydrated rats was not consistently prevented by prior administration of dibenamine or a potent anti-5-hydroxytryptamine substance (Methysergide), to the rats at the time of hydration. Carotid blood from rats under ethanol anaesthesia did not contain detectable antidiuretic activity. After administration of an intravenous dose of reserpine (50 μg/100 g) carotid blood collected at the time of maximum antidiuresis contained a detectable amount of antidiuretic activity which, in four experiments out of five, was destroyed by sodium thioglycollate. This, together with the finding that reserpine prolongs the time to the maximum rate of excretion of urine in hydrated rats, suggests that reserpine releases antidiuretic hormone from the neurohypophysis.

Rate augmentation factor improves initial rate response in the early stages of exercise. Fast response gives an improved time to initial rate increase and shortens the duration of inappropriate postexercise tachycardia. These features improve the pattern of response of the minute ventilation sensor.

Ethanol at 5% and 10% depresses the absorption and excretion of a water load in rats. This depression of diuresis is probably caused by the ethanol-induced acidity, since it was not observed when the gastric acidity was neutralized by administration of aluminium hydroxide concomitant with the ethanol.