[Show abstract][Hide abstract] ABSTRACT: In Japan there are a number of children and adolescents with emotion-related disorders including psychosomatic diseases (orthostatic dysregulation, anorexia nervosa, recurrent pains), behavior problems and school absenteeism. According to our previous report, the Japanese children had significantly higher score of physical symptoms and psychiatric complaints than did the Swedish children, and these were more strongly influenced by school-related stress than by home-related stress. To enforce countermeasures for psychosomatic problems in children, the Japanese Society of Psychosomatic Pediatrics (established in 1982) have started several new projects including multi-center psychosomatic researches and society-based activities. In this article, we present an outline of our study on mental health in Japanese children in comparison with Swedish children. Countermeasures including clinical guidelines for child psychosomatic diseases are reviewed and discussed.
[Show abstract][Hide abstract] ABSTRACT: To investigate the possible involvement of Rho-kinase in cooling-induced contraction of the detrusor muscle. The etiology of diabetic cystopathy is not clear. It may be due to various changes in bladder innervation and/or detrusor muscle dysfunction. Because cooling of urinary bladder smooth muscle normally is a potent stimulus to micturition due to increase in muscle tone, we studied the effects of cooling on normal and diabetic bladder specimens.
Urinary detrusor muscle strips isolated from rats were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to stepwise cooling were examined from normal and 12-week streptozocin-induced diabetic rats. We examined the effects of calcium-free, ethylene glycol bis (beta-aminoethylether)-N,N,N,N,-tetraacetic acid (1 mm)-containing Krebs solution, and the Rho-kinase inhibitor Y-27632 on the cooling responses.
Stepwise cooling from 37 degrees C to 5 degrees C induced a rapid and reproducible increase in basal tone, proportional to cooling temperature. This response was more pronounced in diabetic specimens. Cooling-induced contractions were significantly inhibited in calcium-free solutions in both control and diabetic bladders. Our investigation showed that the influx of extracellular calcium is important in inducing the cooling response. The Rho-kinase inhibitor Y-27632 (1 microm) inhibited cooling (20 degrees C)-induced contraction. It reduced the response by 52.1% +/- 10.0% in control and by 70.0% +/- 12.0% in diabetic rats.
Cooling-induced contractions in control and diabetic detrusor muscle preparations are highly calcium dependant. It also involves activation of Rho-kinase, which might be upregulated in the diabetic detrusor muscle. These results may help in the management of diabetes-induced incontinence due to involuntary detrusor muscle activity.
[Show abstract][Hide abstract] ABSTRACT: The present investigation is about cardiovascular responses and relevant autonomic function in Swedish and Japanese pubertal children on active standing using non-invasive continuous beat-to-beat finger arterial pressure (FAP) monitoring and power spectral analysis. Examined were 54 Swedish and 57 Japanese children (13-15 years). FAP and heart rate (HR) was continuously recorded in the supine position and during standing. Supine FAP was significantly higher in Swedish compared with Japanese children (121/62 versus 103/53 mmHg, P < 0.001). Swedish children showed a higher increase in arterial pressure and HR upon uprising, resulting in a higher vasoconstrictor index (5.04 +/- 0.22 versus 2.31 +/- 0.11 mmHg s(-1), P < 0.001, respectively). There were also higher increases in arterial pressure and HR in the following steady state period (1-7 min) between the two groups. These differences were also found after adjustment of body weight and height. Frequency domain analysis of HR and arterial pressure variability indicated significantly higher low/high frequency power of HR and low frequency power of arterial pressure. These results suggest that Swedish pubertal children have higher basal blood pressure and enhanced cardiovascular sympathetic responses. These differences in the two cohorts might be caused by genetic factors.
[Show abstract][Hide abstract] ABSTRACT: Heatstroke is a serious condition and clinical studies indicate that vascular stroke increases with excessive consumption of alcohol (ethanol). It was our objective to test the influence of ethanol on cerebral perfusion at normal and higher temperatures.
Recording of isometric tension in rabbit carotid artery strips in organ baths with different concentrations of ethanol at 37 degrees C and during hyperthermia (39-43 degrees C) and scintigraphic cerebral imaging of a radioactive isotope in the control situation and during hyperthermia.
Stepwise heating induced reproducible reversible graded contraction, proportional to temperature. At high concentrations (toxic levels), ethanol induced an increase in tension and heating potentiated these responses. Extracellular Mg(2+) potentiated both heat-induced contraction and ethanol-induced contraction while extracellular Ca(2+) had no effect on these responses. During hyperthermia and ethanol scintigraphic isotope uptake was reduced in cortical and cerebellar regions.
Carotid artery vasomotor tone is temperature dependent and heating induces vasoconstriction. Alcohol (ethanol) at 37 degrees C elicited carotid artery contraction at high concentrations (toxic levels) but at any concentration during elevated temperature (39-43 degrees C). Ethanol potentiated the effect of hyperthermia-induced vasoconstriction and reduced cerebral perfusion as shown by radionuclide imaging. The synergistic effect of ethanol and hyperthermia may induce heat stroke and brain damage.
[Show abstract][Hide abstract] ABSTRACT: Research on the pathophysiology and treatment of brain damage with special focus on thermal vascular responses is the subject of this minireview. Interruption of cerebral blood supply by vascular obstruction, temporary cardiac arrest or hyperthermia causes a sudden attack of vascular stroke or heatstroke with serious consequences. It may not induce immediate cell death, but can precipitate a complex biochemical cascade leading to a delayed neuronal loss. When testing thermal vasomotor responses by stepwise cooling of isolated carotid arteries, a temperature-proportional dilatation was observed while heating induced the opposite response: a marked vasoconstriction. General hyperthermia with an increased oxygen demand combined with a reduction of blood supply therefore is a serious consequence. At the cellular level an important mechanism involving hyperthermia is the temperature-dependent regulation of K(+) channel tone of vascular smooth muscle. Further, their inhibition through temperature elevation causes vasoconstriction. In heatstroke, which can induce platelet aggregation and the release of the vasoconstrictor serotonin, arterial cooling attenuates this response. General hypothermia is induced to prevent or attenuate neurological damage in stroke. The procedure is not without serious side effects. Therefore, rapid institution of selective brain cooling has been considered in adults and in infants with postpartum encephalopathy.
Medical Principles and Practice 02/2006; 15(4):316-21. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical experience and experimental studies have shown that hyperthermia can cause cerebral ischaemia and brain damage. By in vitro experiments with heating, we previously were able to induce carotid artery constriction. The objective of the present study was to clarify the mechanism of this thermal response. Isometric tension was recorded in rabbit carotid artery specimens using organ baths during stepwise temperature elevation. The heating responses were investigated at basal tone, in precontracted vessels, after blocking of adrenergic responses and administration of potassium (K)-channel activators and inhibitors. Stepwise heating of carotid artery strips from 37 degrees C to 47 degrees C induced reproducible graded contraction. The hyperthermic responses were not due to adrenergic stimulation, which were reduced and resistant to neurogenic blockade by tetrodotoxin. Heating-induced contractions were potentiated by the K-channel inhibitors tetraethylammonium, BaCl2, charybdotoxin, and the Na+/K+ ATPase inhibitor ouabain. Levcromakalim (BRL), a K+-channel activator, reduced heating induced contractions. Heating of carotid artery preparations induced reversible graded vasoconstriction proportional to temperature. The heating-induced contractions were not mediated by an adrenergenic process, but rather were due to inhibition of K+ channels, which increases Ca2+ entry. In vivo, this reaction may lead to a disturbance of autoregulation of cerebral blood flow and ischemia with brain damage.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 05/2005; 14(3):122-6. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical and experimental studies indicate that hyperthermia can cause heatstroke with cerebral ischemia and brain damage. However, no study has examined the direct effects of heating carotid artery smooth muscle and tested the hypothesis that hyperthermia induces arterial vasoconstriction and, thereby, decreases cerebral blood flow. We recorded isometric tension of rabbit carotid artery strips in organ baths during stepwise temperature elevation. The heating responses were tested at basal tone, in norepinephrine- and KCl-precontracted vessels, and after electrical field stimulation. Stepwise heating from 37 degrees C to 47 degrees C induced reproducible graded contraction proportional to temperature. The responses could be elicited at basal tone and in precontracted vessels. Heating decreased the contractile responses to norepinephrine and electrical field stimulation but increased contraction to KCl. These responses were not eliminated by pretreatment with the neuronal blocker tetrodotoxin. Our results demonstrate that heating carotid artery preparations above 37 degrees C (normothermia) induced a reversible graded vasoconstriction proportional to temperature. In vivo this reaction may lead to a decrease in cerebral blood flow and cerebral ischemia with brain damage as in heatstroke. The heating-induced contraction is not mediated by a neurogenic process but is due to altered transcellular Ca2+ transport. Cooling, in particular of the neck area, therefore, should be used in the treatment of heatstroke.
Journal of Applied Physiology 06/2004; 96(5):1875-8. · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated cardiovascular autonomic function using power spectral analysis of heart rate variation and beat-to-beat finger arterial pressure at rest and while standing and correlated these findings with self-reported psychosomatic and psychosocial symptoms in 122 schoolchildren. Children with three or more psychosomatic and psychosocial symptoms (somatizers) were found to have significantly lower blood pressure than children without symptoms. Somatizers had the more decreased spectral power of the low frequency (LF) band of arterial pressure and RR intervals in the supine position. The high frequency (HF) power did not differ between the two groups. Somatizers showed a more marked reduction in systolic arterial pressure at the onset of standing than did subjects without symptoms but somatizers showed an identical response in systolic arterial pressure when compared to subjects without symptoms during the later stage of standing. The increases in the LF band of arterial pressure and LF/HF of RR intervals during standing were higher in somatizers. These results suggest that somatizers have decreased sympathetic modulation. We conclude that psychosomatic and psychosocial symptoms in children might be associated with low blood pressure and decreased sympathetic modulation.
Clinical Autonomic Research 01/2003; 12(6):477-82. · 1.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical and experimental studies seem to indicate that hypothermia may improve outcome in stroke victims and reduce experimental brain injury. The current interpretation is that cooling has a neuroprotective effect by reducing brain metabolism. The objective of our study was to test the hypothesis that hypothermia induces arterial vasodilatation and thereby increases cerebral blood flow.
We recorded isometric tension in rabbit carotid artery strips in organ baths during stepwise cooling. The cooling responses were tested at basal tone, in noradrenaline-precontracted vessels, and after electric field stimulation.
Stepwise cooling from 37 degrees C to 4 degrees C induced reproducible graded relaxation, inversely proportional to temperature. The responses could be elicited at basal tone and in precontracted vessels. Cooling decreased the contractile responses to norepinephrine and potassium chloride. Cooling at 20 degrees C decreased the contractile responses to electric field stimulation, while at 10 degrees C these were totally abolished. Cooling-induced vasodilatation is not dependent on an endothelial mechanism.
Cooling of carotid artery preparations induced a reversible graded vasodilatation and decreased or abolished the effect of vasocontractile neurotransmitters. The effect of local hypothermia could increase cerebral blood flow and may constitute a positive therapeutic modality in stroke patients.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to determine the effect of cooling on smooth muscle tone of the pulmonary artery and aorta and to clarify the basic mechanism of these responses. We recorded isometric tension in smooth muscle strips of rat pulmonary artery and aorta in organ baths during stepwise cooling. Cooling responses were tested before and after the addition of various standard agents that interfere with known neurogenic (autonomic blockers, tetrodotoxin) and myogenic mechanisms (calcium channel blockers) of relaxation. We also examined the hypothesis of the presence of a cooling-released substance. Stepwise cooling (37degrees C to 4 degrees C) of aortic smooth muscle induced reproducible graded relaxations that were inversely proportional to temperature. Cooling-induced relaxation was not dependent on a neural mechanism nor the release of neurotransmitters or a cooling-released substance such as NO or CO. Cooling of pulmonary arterial and aortic smooth muscle preparations induced a graded myogenic relaxation inversely proportional to the cooling temperature. The mechanism is not dependent on local nervous or known mediators but related to a direct physico-chemical effect of cooling.
Canadian Journal of Physiology and Pharmacology 12/2001; 79(11):899-904. · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the effect of cooling on smooth muscle contraction in various parts of the gastrointestinal tract (esophagus, stomach, duodenum, jejunum and colon) and to investigate the basic mechanism underlying cooling-induced (CIC) tonic and rhythmic contractions. Recordings of isometric tension from smooth muscle strips of different parts of the rat gastrointestinal tract were performed using organ-bath techniques, and stepwise cooling was applied. Cooling was tested before and after the addition of various standard agents interfering with known neurogenic (autonomic blockers, tetrodotoxin, capsaicin) and myogenic mechanisms of contraction (calcium channel blockers, Sarcoplasmatic and Ca2+-ATPase pump inhibitors). Step-wise cooling (37 degrees C to 5 degrees C) of all gastrointestinal smooth muscle preparations induced reproducible graded tonic contractions, inversely proportional to temperature. CIC was most pronounced in the jejunum. Cooling abolished rhythmic smooth muscle activity. CIC was not dependent on a neural mechanism nor the release of neurotransmitters, but linked to translocation of calcium. It was reduced by incubation in Ca2+-free solution. Blockage of the Ca2+-ATPase pump, which inhibits the extrusion of calcium, plays a significant role in the process and enhances CIC. Cooling of gastrointestinal smooth muscle preparations induces graded myogenic contractions inversely proportional to the temperature. The mechanism is not dependent on local nervous control but related to a temperature-sensitive process of calcium translocation.
Fundamental and Clinical Pharmacology 11/2001; 15(5):349-54. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between blood pressure levels and cardiovascular autonomic function in adolescents and preadolescents.
We measured variability of beat-to-beat arterial pressure and R-R intervals using power spectral analysis in 56 adolescents (aged 13-16 years; mean age, 9.0 +/- 1.4 years) and 71 preadolescents (6-12 years; mean age, 13.5 +/- 1.1 years) in the supine and standing positions.
Adolescents had higher levels of systolic arterial pressure and lower high-frequency power of RR intervals than preadolescents. Correlation between the basal level of arterial pressure and autonomic function was observed in adolescents but not in preadolescents. In adolescents, multivariate analysis indicated that the basal level of arterial pressure was inversely related with the high-frequency power of RR intervals and positively with the ratio of low-frequency and high-frequency power. No significant relation was found in preadolescents. During standing, adolescents had a more marked increase in diastolic arterial pressure, heart rate, low frequency of R-R intervals, and low frequency of arterial pressure compared with those of preadolescents. Changes in diastolic pressure showed a significant negative correlation with changes in high frequency of R-R intervals.
Cardiovascular autonomic function plays an important role in increasing blood pressure levels associated with increased modulation of vagal tone of the heart after puberty but does not in the preadolescent.
Journal of Pediatrics 08/2000; 137(1):63-7. · 3.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: It is known that the macrolide antibiotic erythromycin stimulates gastrointestinal and gallbladder motility by an as yet unidentified mechanism. It was the objective of this study to investigate the mechanism of the gallbladder motility-stimulating effect of erythromycin. Methods: In our experiments we used strips of sheep gallbladders measuring isometric tension in organ baths. Since erythromycin itself did not induce contraction we examined the prokinetic effects of sheep duodenal extract, incubated with (DEX) or without (blank) erythromycin (10–5M). Results: Both DEX and blank elicited gallbladder contraction associated with heat-stable, water-soluble but not with lipid-soluble duodenal prokinetic factor. The factor is unrelated to motilin or cholecystokinin and is only partially (
Medical Principles and Practice 01/2000; 9(1):74-80. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detrusor muscle contraction and uninhibited micturition after intravesical instillation of ice water is interpreted as a sign of upper motor neuron lesions. The basic mechanism of cooling-induced contraction (CIC) at the level of smooth muscle, however, has not been satisfactorily explained. We therefore designed model experiments with cooling of rat detrusor muscle.
We recorded isometric tension from strips of rat urinary detrusor muscle in organ baths during stepwise cooling. CIC was tested before and after addition of various standard agents interfering with known neurogenic (autonomic blockers, tetrodotoxin, capsaicin) and myogenic mechanisms of contraction (calcium channel blockers).
Stepwise cooling (37 degrees to 5 degrees C) of detrusor muscle induced reproducible graded contractions, inversely proportional to temperature. CIC was not dependent on a neural mechanism (not blocked by tetrodotoxin or capsaicin) or the release of neurotransmitters but was linked to translocation of calcium. It was reduced by calcium channel blockers and Ca(2+)-free solution. Blockage of the Ca(2+)-adenosine triphosphatase pump, which inhibits the extrusion of calcium, also plays a significant role in the process and enhances CIC.
Cooling of detrusor muscle preparations induces a graded myogenic contraction inversely proportional to the temperature. The mechanism is not dependent on local nervous control but is related to calcium translocation.
[Show abstract][Hide abstract] ABSTRACT: — The purpose of this study was to characterize β-adrenoceptor subtype(s) mediating relaxation in smooth muscle strips of the sheep gallbladder. Experiments were performed on isolated smooth muscle strips suspended in tissue baths containing Krebs' solution. Isoprenaline (10−8 M-10−5 M) and salbutamol (10−7 M-10−4 M) produced concentration-dependent relaxation of carbachol (10−7 M-3 × 10−7 M) contracted smooth muscles of the sheep gall bladder. Isoprenaline-induced relaxation was significantly antagonized by propranolol with -logKB values of 7.81 ± 0.11 (n = 7) and 7.73 ± 0.12 (n = 6) in the fundic and ductal strips respectively. Atenolol (10−5 M), a selective β1- adrenoceptor antagonist, also significantly antagonized isoprenaline-induced relaxation with -logKB values of 5.82 ± 0.11 and 6.09 ± 0.09 in the fundic and ductal strips respectively. However, ICI 118551, a selective β2-adrenoceptor antagonist, at concentrations up to 10−6 M had little or no effect on isoprenaline-induced relaxation in either of these preparations. BRL 37344A, a selective β3-adrenoceptor agonist produced concentration-dependent relaxation of carbachol-precontracted fundic and ductal strips. BRL 37344 was approximately 9-fold more potent in the ductal than fundic strips. In both preparations, BRL 37344-induced relaxation was not significantly (p > 0.05) antagonized by propranolol (3 × 10−7 M). This would confirm that the response was mediated via β3-adrenoceptors. It was concluded that β1- and β3-adrenoceptors coexist in the sheep gallbladder and mediate smooth muscle relaxation.
Fundamental and Clinical Pharmacology 03/1999; 13(2):187-192. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to assess the relaxant responses of salbutamol, a beta2 agonist, and forskolin, an activator of adenylate cyclase, and the possible role of forskolin in reversing tachyphylaxis to salbutamol. The in-vitro bronchodilator effects of salbutamol and forskolin (10(-9)-10(-5) M) were tested on isolated guinea-pig tracheal rings precontracted with carbachol (10(-7) M). Both salbutamol and forskolin elicited concentration-dependent relaxation. Potency (EC50; the dose resulting in 50% relaxation) was determined from cumulative concentration-response curves. Salbutamol was more potent than forskolin in relaxing the tracheal preparations (-log molar EC50 7.68+/-0.14 and 6.3+/-0.17, respectively). Reproducible relaxant responses to salbutamol could be elicited after 24 h incubation in Krebs solution. Tachyphylaxis to the relaxant effects of salbutamol was experimentally induced by incubation (24h) of the preparations in Krebs solution containing salbutamol (10(-6) 3x10(-6) or 10(-5) M). This pretreatment of the tissues resulted in a significant reduction in the potency of salbutamol. The potency of salbutamol was reduced to 6.85+/-0.2, 6.8+/-0.1 and 5.9+/-0.27 after 24h incubation with salbutamol 10(-6), 3x10(-6) or 10(-5) M, respectively. The potency of salbutamol was increased from 7.35+/-0.2 to 7.76+/-0.28 by addition of forskolin (3x10(-7) M) under control conditions. Moreover, forskolin (3x10(-7) M) reversed the development of tachyphylaxis to salbutamol-induced relaxation in tissues pretreated with salbutamol. The potency of salbutamol was increased to 7.29+/-0.41, 7.37+/-0.17 and 7.23+/-0.35 after the addition of forskolin (3x10(-7) M) to preparations pre-incubated (24h) with salbutamol 10(-6), 3x10(-6) or 10(-5) M respectively. These results show that in guinea-pig tracheal ring preparations, forskolin shares with salbutamol the ability to relax airway smooth muscle and produces an apparent reversal of tachyphylaxis to the bronchodilator effects of salbutamol, particularly in the low concentration range. This effect could provide an alternative therapy for long term use, particularly with high doses of beta2 agonists in bronchial asthma.
Journal of Pharmacy and Pharmacology 03/1999; 51(2):181-6. · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the ultrastructure of the local nerve supply of ovine gallbladders as well as the functional characteristics of inhibitory nerves. We used electron microscopy of thin sections of ovine gallbladders and in vitro isometric tension recording using gallbladder strips. Specifically, we measured contractile and inhibitory responses induced by transmural electrical field stimulation (EFS). We found a ganglionated plexus with intramural nerve cells and interconnecting axons. Clear and large dense-core vesicles colocalized in axons close to smooth muscle cells. EFS elicited gallbladder contractions which were converted to relaxation after atropine. EFS-induced relaxation was reduced by the nitric oxide (NO) synthase inhibitor, L-NOARG and blocked by propranolol and/or tetrodotoxin. In conclusion, enteric ganglia and neurones with synaptic vesicles (clear and dense core) were detected close to smooth muscle bundles. Neural inhibition of gallbladder contraction was mediated by beta-adrenoceptors coupled to NO generation.