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Biomedical subjects

H Berthold

Publications and source records attributed to H Berthold.

At least 73 records · Page 4Linked to original sources

Identification of cardiotonic sodium channel activators by potassium depolarization in isolated guinea-pig atria.

The inotropic actions of various drugs known to increase force of contraction in isolated mammalian cardiac muscle were investigated in electrically driven (1 Hz) guinea-pig left atria under both normal [K+]o (4.7 mM) and high [K+]o (22 mM). Under normal [K+]o a concentration-dependent increase in force of contraction could be confirmed with the beta-adrenoceptor agonist, isoprenaline, the cyclase activator, forskolin, the inhibitors of the cyclic AMP-phosphodiesterase (PDE), amrinone, IBMX, and OPC 8212, the Na+ channel activators, DPI 201-106, SDZ 210-921, veratridine, and ATX II, the Na(+)-ionophore monensin, the inhibitor of Na+/K(+)-ATPase, ouabain, and the Ca2+ channel activators, Bay K 8644, CGP 28 H 392, and SDZ 202-791. Partial depolarization of the muscle preparations by increasing [K+]o in the organ bath to 22 mM completely abolished the positive inotropic action of the Na+ channel-activating drugs. In contrast, the effects of the other compounds were still present, although changes in the maximal force development were observed. The efficacy of the PDE inhibitors amrinone and IBMX were slightly increased; the maximal effects of isoprenaline, monensin, forskolin, and OPC 8212 were unchanged; the effect of ouabain decreased to about half maximal values; while the efficacy of the Ca2+ channel activators were either unchanged (CGP 28 392) or decreased (Bay K 8644 and SDZ 202-791). The results suggest that inactivation of cardiac fast Na+ channels by partially depolarizing isolated, electrically driven atria is a suitable model to distinguish between cardiotonic agents acting through activation of Na+ channels and those with other mechanisms of action.

1-Methyl-3-isobutylxanthine↗

Suspected periodontopathogens in erupting third molar sites of periodontally healthy individuals.

29 periodontally healthy subjects (11 female and 18 male) with a mean age of 24 years (range 19 to 38 years) and with partially erupted lower third molars participated in this study. 18 subjects demonstrated no signs or symptoms of acute inflammation and were without pain (group A). 5 subjects showed redness of the pericoronal tissues and experienced pain upon palpation (group B). 6 subjects suffered from acute pain and exhibited formation of pus (group C). Microbiological samples were taken from the lateral aspect of the pericoronal space using the paperpoint-method. Continuous anaerobic techniques were utilized for microbiological processing. The samples were cultivated on ETSA and on selective media and were studied by darkfield microscopy. Gram-negative anaerobic rods accounted for 27% (group A), 34% (group B) and 39% (group C) of all organisms growing on ETSA. Bacteroides intermedius was detected in 61% (group A), 80% (group B) and 83% (group C) of the samples. B. gingivalis was found in 1 sample of group A only. Fusobacterium sp. was detected in 56% (group A), 80% (group B) and 33% (group C) of the samples. Capnocytophaga were seen in 67% (group A), 20% (group B) and 50% of the samples. Actinobacillus actinomycetemcomitans was found in 44% (group A), 40% (group B) and 17% (group C). 72% of the group A and 100% of the group B and C samples contained spirochetes. In all of those positive samples, small spirochetes were present, but only 78% contained medium and only 48% large spirochetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

5-HT1 receptor agonists attenuate the naloxone-induced jumping behaviour in morphine-dependent mice.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and RU 24969 have been used to investigate whether 5-HT1A and 5-HT1B receptors are involved in the naloxone-induced jumping behaviour of the chronically morphine-dependent mouse. To control for possible interactions with catecholaminergic systems, the effects of alpha 1- and alpha 2-adrenoceptor antagonists were investigated. 8-OH-DPAT and RU 24969, as well as buspirone, ipsapirone and flesinoxan, were found to suppress jumping. The effects were mimicked by the alpha-adrenoceptor antagonists, idazoxan, WY 26392, yohimbine and rauwolscine. Inhibition of 5-HT synthesis with para-chlorophenylalanine (pCPA) had only minimal effects on withdrawal jumping per se; the attenuating effects of 8-OH-DPAT and RU 24969 were not altered in pCPA-pretreated animals. The effects of RU 24969 were blocked by (-)-pindolol and, stereoselectively, by (-)-SDZ 21-009. (-)-Pindolol neither influenced the action of 8-OH-DPAT nor showed any effect per se. The actions of 8-OH-DPAT and buspirone, but not of RU 24969 and idazoxan, were blocked by the 5-HT1A receptor antagonist, spiroperidol. Similarly, both haloperidol and prazosin prevented the attenuating action of 8-OH-DPAT but did not interfere with the action of RU 24969. We conclude that the actions of 8-OH-DPAT and RU 24969 are mediated by postsynaptic receptors. The 5-HT1B receptor appears to mediate the attenuating action of RU 24969; the exact mechanism of action of 8-OH-DPAT remains open but activation of an alpha 1-adrenoceptor is implicated.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Cardiovascular effects of endothelin 1 in pithed spontaneously hypertensive rats: evaluation of its mechanism(s) of action.

The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1-3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals "died" following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC50 2.1 +/- 0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 microgram/kg i.v.), phenylephrine (8 micrograms/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca2+ channels.

Angiotensin II↗

Inhibition of the 5-HT-induced cardiogenic hypertensive chemoreflex by the selective 5-HT3 receptor antagonist ICS 205-930.

We investigated the effect of ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], a selective antagonist at 5-HT3 receptors, on the cardiogenic hypertensive chemoreflex in the anaesthetized dog. The reflex was elicited by injection of 5-HT (12.5-1600 micrograms) into the left cardiac ventricle and consisted of a dose-dependent systemic hypertension associated with a decrease in heart rate. ICS 205-930 (10, 30, and 100 micrograms/kg i.v.) caused a displacement to the right of both the dose-response curves of 5-HT-induced blood pressure increase and heart rate reduction. Its blocking effects upon the action of 5-HT could be surmounted by increasing the dose of the agonist. The selective 5-HT2 receptor antagonist, ketanserin (0.1 mg/kg i.v.) and the combined 5-HT1 and 5-HT2 receptor antagonist, methiothepin (0.1 mg/kg i.v.) had no influence on the hypertensive reflex. When the reflex was elicited by the ganglionic stimulant, 1,1-dimethyl-4-phenyl-piperazinium (DMPP; 100-1600 micrograms), ICS 205-930 had no blocking effect. The results suggest that the 5-HT-induced cardiogenic hypertensive chemoreflex is mediated by 5-HT3 receptors.

Animals↗

Enigmatic action of ciclosporine A on the naloxone-precipitated morphine withdrawal syndrome in mice.

Various alterations of the immune system have recently been reported to attenuate the severity of morphine withdrawal. The effect of the immunosuppressive agent ciclosporine A on the naloxone-induced morphine withdrawal syndrome in the chronically dependent mouse was investigated. Ciclosporine A significantly suppressed stereotyped behaviour such as jumping and forepaw treading while wet shakes were potentiated. Withdrawal diarrhoea was diminished as a consequence of a promotive action of ciclosporine A on the intestine. A ciclosporine derivative, which is devoid of immunosuppressive activity, had no influence on withdrawal signs. The attenuating effect of ciclosporine A was observed at a dose of 20 mg/kg i.p., which is not regarded as immunosuppressive in the mouse. It was also effective in animals lacking an intact immune system as a result of a genetic T-cell defect (nude mouse) or after selective ablation by whole body irradiation. Nude mice and irradiated normal mice developed dependence on morphine to the same extent as normal animals, as could be derived from the severity of their withdrawal signs. These results suggest that an intact immune system is not a necessary prerequisite for ciclosporine A to attenuate morphine withdrawal and that its action may be attributable to mechanisms other than immunosuppression. It is possibly a result of a direct effect of ciclosporine A on the central nervous system structures involved in the behavioural expression of the opiate withdrawal syndrome.

Animals↗

Antidiuretic effect of Sandostatin (SMS 201-995) in healthy volunteers.

Ten male healthy volunteers were studied in order to determine whether the synthetic somatostatin analogue Sandostatin (SMS 201-995) has effects similar to those of natural somatostatin on renal water and electrolyte excretion. The study was carried out in three separate placebo-controlled randomized double-blind cross-over trials. The subjects received single sc injections of 100 micrograms Sandostatin and placebo under conditions of mild diuresis (trial 1), water load with enhanced diuresis (trial 2), and water load with exogenous lysin-vasopressin (5 IU sc) induced antidiuresis (trial 3). The following parameters were measured: urine flow rate, serum and urine osmolalities, osmolar clearance, free water and creatinine clearances, excretion rates of sodium, potassium, calcium, chloride, and phosphate, and immunoreactive insulin. A marked antidiuretic effect was observed within 2 h after dosing in all three trials. Urine flow rates were reduced by 45% in trial 1 and by 29 and 31% in trials 2 and 3, respectively (all P less than 0.05). There were no differences in effects on serum and urine osmolalities between Sandostatin and placebo. Osmolar clearance was significantly reduced in trial 1 (P less than 0.01). Free water clearance significantly decreased only in trial 2 (P less than 0.05). Sodium excretion decreased by 49, 48 and 67%, respectively, the differences being significant in trials 1 and 3 (P less than 0.05). Calcium excretion decreased by 66, 70 and 54% (all P less than 0.001). Chloride excretion decreased by 28, 22 and 44%, the differences being significant in trials 2 and 3 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intermittent nursing home care. Development of an alternative to institutional care.

Intermittent care was offered as an alternative to 178 patients who were at risk of permanent nursing home care, and this proved to be feasible for 55% of these patients. Non-participation was most common due to a pronounced deterioration of health status, hesitance or sick relatives. A more detailed evaluation of this form of long-term care was made for the 27 patients who were in the programme at a specific time and were able to participate in an interview. Although the patients had advanced medical problems and disabilities (80% had balance problems, 74% urinary incontinence, etc.) the majority had a positive outlook on life and appreciated intermittent care. Also from a clinical aspect this form of long-term care proved acceptable, although a decline in performance of activities of daily living and health status was frequently observed during the periods at home.

Activities of Daily Living↗

Home care and intermittent care--a realistic alternative to nursing-home care?

An inventory was made among 210 elderly nursing-home patients to investigate the feasibility of exchanging their permanent stay in the nursing home for another form of care and whether they wanted to. The main alternative was intermittent nursing-home care. The patients were assessed as to physical and mental health and social conditions. The majority (62.7%) were considered too ill for other than nursing-home care. In some patients (24.8%) there were social factors, the main one being that they no longer had a home of their own. However, 26 patients (12.4%) were recommended for intermittent care, but only three were interested. From these results it was concluded that if intermittent home care is to represent a realistic alternative it should be offered to the patients before they move into a nursing home.

Aged↗

Intermittent care for old patients--when should it be offered?

An inventory was made among 229 elderly individuals in out- and in-patient care, community care and social welfare. The aim was to investigate the patients' possibilities and interest for intermittent nursing home care in order to avoid or postpone permanent institutional care. The patients were assessed as to physical and mental health and social conditions. Intermittent care was thought to be appropriate for 81 of these patients (35%). After an interview of the patients and cohabiting relatives, 21 patients (9%), mainly out-patients, took a positive interest in this form of care. The in-patients were mostly too ill, and patients in community care found intermittent care interesting but were not prepared for this form of rehabilitation and preferred to wait despite risk of acute deterioration. The most suitable and interested patients and relatives were found among those in day hospital and those on the waiting list for geriatric care.

Aged↗