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Biomedical subjects

P Ylitalo

Publications and source records attributed to P Ylitalo.

At least 19 recordsLinked to original sources

Acute neurobehavioural toxicity of trichothecene T-2 toxin in the rat.

The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T-2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T-2 toxin increased motionlessness and decreased sniffing (P less than 0.05) 4 hr after the administration. The higher dose shortened step-through latencies in the test trial of the 24-hr passive avoidance test (two-way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T-2 toxin was only 25% of that in controls (P less than 0.001). T-2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7-8 hr after administration. T-2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T-2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance test at dose 2.0 mg/kg.

Animals

Acute neurobehavioural effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han/Wistar rats.

The neurobehavioural effects of a single non-lethal dose (1000 micrograms/kg intraperitoneally) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were assessed in young male Han/Wistar rats, highly resistant to acute lethality of TCDD. TCDD decreased body weight significantly compared with ad libitum fed controls. TCDD did not change the behaviour or the motility of rats in the open field test 8 days after the treatment nor did it affect the spontaneous motor activity up to 27 days after the exposure. In the elevated plus-maze test for anxiety, TCDD-treated rats did not differ from either ad libitum fed controls or pair-fed controls. In the 24-hr passive avoidance test, the learning of TCDD-treated rats did not differ significantly from that of ad libitum fed controls or pair-fed controls from 8 hr to 16 days after the treatment. TCDD did not affect the motor coordination or the maintenance of balance on the rotating rod but it impaired them slightly in the elevated horizontal bridge test 16 hr after exposure. It did not affect nociception in the hot plate test 16 hr or 8 days after the injection. The results suggest that a single sublethal dose of TCDD does not alter markedly the general behaviour of Han/Wistar rats, in contrast to its striking effect on feeding behaviour which results in a marked decrease in body weight gain.

Animals

The effects of a beta 1-blocking agent, atenolol, on blood pressure, plasma renin activity and prostaglandin F2 alpha excretion in patients with essential hypertension.

The antihypertensive action of beta-blocking agents has been suggested to be associated with the decrease in plasma renin activity (PRA) and can be antagonized by indomethacin, a prostaglandin (PG) synthesis inhibitor. We studied the acute and long-term effects of a beta 1-blocking agent, atenolol (50 mg b.i.d.), on blood pressure (BP), PRA and urinary PGF2 alpha excretion in 12 male patients (40 years old) with essential hypertension. BP was measured by means of a brachial cuff. PRA and PGF2 alpha were estimated radioimmunologically. One day after the initiation of atenolol treatment, BP fell significantly, the supine values from 159/114 to 143/104 mmHg and the erect from 158/118 to 140/106 mmHg. In six weeks BP decreased further to 135/94 and 134/96 mmHg, respectively. After the cessation of atenolol for three weeks BP rose to the pre-atenolol level. When the dose was readjusted (25-150 mg daily for 26 weeks), diastolic BP remained at 100 mmHg or higher in only two patients. During the atenolol treatment PRA declined to one-third of the pre-atenolol level in one day and to one-half in six weeks. The urinary excretion of PGF2 alpha was not affected by atenolol. Our results suggest that 1) the antihypertensive action of atenolol and the reduction of PRA are substantial already in one day, and 2) the decrease in BP or PRA is not associated with PGF2 alpha production.

Adult

Hemodynamic changes during the development of sodium-induced hypertension in subtotally nephrectomized rats.

Hemodynamic changes during the development of sodium-induced hypertension were investigated in male Sprague-Dawley rats after about 70% of the renal mass was removed. Throughout the four experimental weeks, subtotally nephrectomized rats on a high sodium diet (750 mEq/kg) showed a continuous rise in blood pressure up to the mean value of 178 +/- 9 mmHg. In sham-operated animals on the high sodium supply the blood pressure did not increase as compared to sham-operated controls on the standard sodium diet (150 mEq/kg). In the hypertensive group, the primary changes were urea retention and a concomitant increase of serum osmolarity, but the serum sodium concentration remained at the normal level. These changes were followed by sustained enlargement of extracellular fluid and relative intravascular volumes, together with a simultaneous increase of heart rate and blood pressure. During high sodium intake, the plasma renin activity in subtotally nephrectomized rats was suppressed to one fifth of that in sham-operated animals, but the renin substrate activity did not increase markedly.

Animals

Prostaglandins in the regulation of circulation and blood pressure.

Endogenous prostaglandins (PGs) participate in the regulation of local circulation, and presumably also in the control of systemic blood pressure. Vasodilatory PGs synthesized in resistance vessels seem to maintain the basal blood flow in some tissues. Vasoconstriction stimulates the PG synthesis in vessel walls, and the vasodilatory PGs antagonize this constriction in several vascular beds. Circulating vasodilatory PGs or their metabolites may function as antihypertensive hormones. Reports on the effect of intrarenal PG production on renal function are contradictory. The renin-angiotensin-aldosterone and kallikrein-kinin systems have complex interrelations with PGs. PGs may also participate in the mechanism of action of some cardiovascular drugs.

Aldosterone

The effect of inhibition of prostaglandin synthesis on plasma renin activity and blood pressure in essential hypertension.

The influence of oral indomethacin treatment (75 mg daily for a week) on urinary excretion of prostaglandin (PG) F2alpha, plasma renin activity (PRA), blood pressure (BP) and electrolyte excretion (Na+ and K+) was studied in 21 patients with untreated essential hypertension (9 women and 12 men, aged from 40 to 45 years). PGF2alpha excretion and PRA were markedly suppressed by indomethacin in both sexes. A close correlation was found between the decreases in PGF2alpha excretion and PRA. 13,14dihydro-15keto-PGF2alpha (a metabolite of PGF2alpha) excretion also tended to be lowered during the indomethacin treatment. BP tended to increase but urine volume and electrolyte excretion were unchanged during the indomethacin period. The results suggest that in essential hypertension inhibition of the PG synthesis causes a concomitant suppression in PRA and may slightly increase BP.

Adult

The effects of antihypertensive medication on the control of the cardiovascular system during halothane anaesthesia in rats.

The effects of hydralazine, clonidine, propranolol and methyldopa medication on the control of the circulatory system during halothane anaesthesia were studied in spontaneously hypertensive (SH) rats. Special attention was directed to the problem of circulatory emergencies. Under 1 and 3% halothane anaesthesia, the mean arterial pressure was lowest in methyldopa-treated rats. During 3% anaesthesia, plasma renin activity was markedly increased in the methyldopa group and decreased in the propranolol group. Hydralazine medication suppressed the pressor responses to dopamine and metaraminol, whereas clonidine, propranolol and methylopa increased the response to dopamine. These sympathetic agents induced more cardiac arrhythmias in SH controls than in normotensive ones. These arrhythmias were antagonized by hydralazine. The SH controls also tolerated haemorrhagic shock more poorly than did normotensive control rats. Among the pretreated animals, tolerance to this shock was highest in hydralazine-and clonidine-treated animals and lowest in the methyldopa group. The results suggest that during halothane anaesthesia SH rats are more prone to disturbances in the control of circulation than are normotensive controls. Hydralazine and, to a lesser extent, clonidine have a protective action against these disturbances, but the effect of methyldopa seems to be disadvantageous.

Anesthesia, Inhalation

Effect of exercise on the serum level and urinary excretion of tetracycline, doxycycline and sulphamethizole.

The serum level and urinary excretion of sulphamethizole, tetracycline and doxycycline were studied in healthy volunteers subjected to intensive exercise and bed rest in a cross-over trial. Each group consisted of 7--8 subjects. The exercise or bed rest began 15 min before oral administration of the drug and was continued for the following 4 hours. During exercise serum drug concentration and the area under the serum concentration-time curve for each agent was significantly higher (p less than 0.05) than the corresponding values at rest. Exercise greatly suppressed the renal excretion of tetracycline and doxycycline, but the decrease alone appeared insufficient to account for the pronounced increase in serum drug concentration. Total drug excretion in urine was unchanged. Thus, it seemed most unlikely that overall absorption from the gastrointestinal tract had been altered by exercise. However, the rate of absorption appeared to be more rapid in the exercise than in the rest period. Marked haemoconcentration was not produced by the exercise. In addition to changes in absorption and elimination rates, alteration in the volume of distribution might contribute to the higher serum drug concentration during exercise. Therefore, the level of physical activity should be considered in the interpretation of pharmacokinetic data both in clinical practice and in pharmacokinetic studies.

Adult

The poor reactivity of retinal vessels to systemic administration of vasoactive agents in pentobarbital anesthetized rats.

The responsiveness of retinal vasculature to i.v. administration of several potent vasoactive agents was studied in pentobarbital anesthetized rats by taking fundus photographs. Since cerebral vasculature had been claimed to react in a similar manner but less liably than retinal vessels to some vasoactive substances, the findings were applied to the problem of reactivity of brain vessels. Sublethal doses of noradrenaline, adrenaline, 5-hydroxytryptamine, angiotensin amide and arginine orlysine vasopressin caused no marked acute ( less than or equal to 2 min) vasoconstriction in retinal vessels. Nor did any of these agents or bradykinin elicit vasodilatation. The late vasoconstriction (greater than 2 min) found in succumbing animals was most likely unspecific, since it did not occur until severe toxic symptoms appeared. The findings support the concept that intracerebral vessels are quite resistant to the direct action of many vasoactive agents given i.v.

Animals

Oversaturation of urine with sulphadiazine during treatment with a small therapeutic dose.

The urinary crystallization of N1-pyrimid-2-yl-sulfanilamide (sulphadiazine, Sulfolex) during treatment with a small therapeutic dose (600 mg/day p.o.) for 6 days was evaluated in seven voluntary female subjects. In 5/7 and 3/7, respectively, of the urine supernatants obtained from samples collected 6 and 24 h after the last dose of sulphadiazine, the sulphonamide concentration exceeded the experimental solubility of the drug in 37 degrees C urine at the same pH. However, only in 3 sediments of the 6-h urine samples could a few sulphadiazine crystals be found. The findings suggest that the urine often can be oversaturated in respect to sulphadiazine, without any marked crystallization.

Adult

Effect of ketamine anaesthesia on the content of monoamines and their metabolites in the rat brain.

The effects of ketamine anaesthesia (100 mg/kg i.p.) on the content of brain 5-hydroxytryptamine (5HT), 5-hydroxyindoleacetic acid (5HIAA), noradrenaline (NA), dopamine (DA) and homovanillic acid (HVA) were studied in male Wistar rats. Fifteen min after ketamine injection, when the rats were deeply anaesthetized, the 5HT content in many brain regions tended to be increased. An opposite tendency was found in the brain 5HIAA content. In rats treated with probenecid, which markedly lengthened ketamine anaesthesia, the accumulation of 5HIAA was significantly reduced by ketamine. In addition to ketamine anaesthesia, probenecid was found to lengthen thiopental anaesthesia. One hour after the ketamine administration, when the rats were no longer anaesthetized but were excited, the brain NA concentration was increased by 17% (P less than 0.02). The brain DA content was unchanged, but at 15 min and 1 hour after ketamine administration the striatal HVA content was increased by about 55% (P less than 0.05), suggesting an increased turnover of DA. The results suggest that during recovery from ketamine anaesthesia the increased NA content and the increased DA turnover may be associated with the postanaesthetic excitement of the rat, whereas the decreasamine anaesthesia.

Anesthesia, General

[First aid at medical congresses].

The sixth International Congress of Pharmacology in Helsinki, July 1975, was held on a campus area 5 km from the nearest hospital. The congress was attended by 2 600 active participants and one thousand social members, traveling from 54 countries. The equipment at the Congress first aid station allowed for all kinds of emergency treatments, ranging from the care of minor complaints to cardiopulmonary resuscitation. A mobile intensive care unit was kept outside the station throughout the day and was also available at the major social events in the evening. The great majority of the symptoms necessitating a visit to the station were minor complaints. Most participants received their medication direct from the first aid station, the most common drugs being mild analgesics, anticholinergics and antibiotics. According to our experience, at a congress with 3 500 participants it is sufficient to have one physician present at the first aid station, or at least on call, and one to three additional first aid assistants. In general, it is of utmost importance to make adequate plans for the provision of medical as well as dental care at large congresses.

Congresses as Topic

Central pressor actions of angiotensin II.

Involvement of the area postrema in experimental hypertension has been investigated. Ablation of the rear apex of the fourth brain ventricle (=the region of the area postrema) elevated blood pressure, heart rate and plasma angiotensin II level. The same characteristic changes were seen in the two kidney Goldblatt rat model of hypertension. A possible involvement of the area postrema in this model of hypertension is discussed. Intraventricular perfusion of angiotensin II elevated blood pressure without a significant change in heart rates. This pressor response appeared to be dependent on release of antidiuretic hormone. The results are discussed in relation to the intrinsic brain angiotensinogenase system.

Angiotensin II