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Biomedical subjects

M Kitayama

Publications and source records attributed to M Kitayama.

At least 19 recordsLinked to original sources

Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues c[Cys10,14]N/OFQ(1-14)NH2 and c[Nphe1,Cys10,14]N/OFQ(1-14)NH2.

In this study we describe the activity of two cyclic nociceptin/orphanin FQ (N/OFQ) peptides; c[Cys(10,14)]N/OFQ(1-14)NH(2) (c[Cys(10,14)]) and its [Nphe(1)] derivative c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH(2) (c[Nphe(1),Cys(10,14)]) in native rat and mouse and recombinant human N/OFQ receptors (NOP). Cyclisation may protect the peptide from metabolic degradation. In competition binding studies of rat, mouse and human NOP the following rank order pK(i) was obtained: N/OFQ(1-13)NH(2)(reference agonist)>N/OFQ=c[Cys(10,14)]>>c[Nphe(1)Cys(10,14)]. In GTPgamma(35)S studies of Chinese hamster ovary cells expressing human NOP (CHO(hNOP)) c[Cys(10,14)] (pEC(50) 8.29) and N/OFQ(1-13)NH(2) (pEC(50) 8.57) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. Following 30 min pre-incubation c[Nphe(1)Cys(10,14)] competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pA(2) and slope factor of 6.92 and 1.01 respectively. In cAMP assays c[Cys(10,14)] (pEC(50) 9.29, E(max) 102% inhibition of the forskolin stimulated response), N/OFQ(1-13)NH(2) (pEC(50) 10.16, E(max) 103% inhibition) and c[Nphe(1)Cys(10,14)] (~80% inhibition at 10 microM) displayed agonist activity. In the mouse vas deferens c[Cys(10,14)] (pEC(50) 6.82, E(max) 89% inhibition of electrically evoked contractions) and N/OFQ(1-13)NH(2) (pEC(50) 7.47, E(max) 93% inhibition) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. c[Nphe(1)Cys(10,14)] (10 microM) competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pK(B) of 5.66. In a crude attempt to assess metabolic stability, c[Cys(10,14)] was incubated with rat brain membranes and then the supernatant assayed for remaining peptide. Following 60 min incubation 64% of the 1 nM added peptide was metabolised (compared with 54% for N/OFQ-NH(2)). In summary, we report that c[Cys(10,14)] is a full agonist with a small reduction in potency but no improvement in stability whilst c[Nphe(1)Cys(10,14)] displays tissue (antagonist in the vas deferens) and assay (antagonist in the GTPgamma(35)S assay and agonist in cAMP assay) dependent activity.

Animals↗

A marked decrease in bispectral index with elevation of suppression ratio by cervical haematoma reducing cerebral perfusion pressure.

A 77-year-old man with a ruptured abdominal aortic aneurysm undergoing aneurysmectomy were anaesthetised with ketamine under bispectral index (BIS) monitoring, which is a clinical EEG monitor for measurement of depth of anaesthesia/sedation. First marked BIS reduction with elevation of suppression ratio (SR) was observed following severe hypotension by deflation of the aortic occlusion balloon. The re-inflation and rapid blood transfusion improved haemodyanamics and BIS and SR. At second marked BIS reduction with SR elevation, a heavy cervical swelling due to a massive subcutaneous haematoma around the previously mis-punctured right carotid artery extending throughout the whole neck was observed without hypotension. Cervical relief incision improved the BIS and SR. The present case suggests that BIS monitor may be a simple and convenient monitor for cerebral ischaemia detection.

Aged↗

Effects of nicardipine and diltiazem on the bispectral index and 95% spectral edge frequency.

BACKGROUND AND OBJECTIVE: Previous studies have shown that L-type voltage-sensitive Ca2+ channel blocking agents increased and the L-type Ca2+ channel activator Bay K 8644 reduced the general anaesthetic potency in animals. As the bispectral index correlates with the depth of sedation, we examined whether L-type Ca2+ channel blocking agents affect the bispectral index. METHODS: Thirty hypertensive patients (systolic arterial pressure >160 mmHg) presenting for total intravenous anaesthesia with propofol, fentanyl and ketamine were recruited. Bispectral index monitoring was commenced directly the patients arrived in the operating theatre. All patients were given either nicardipine or diltiazem intravenously at the discretion of the anaesthesiologist in charge. RESULTS: Twenty-three and seven patients received nicardipine or diltiazem, respectively. The bispectral index level (mean (95% confidence interval)) did not change with either drug. In the nicardipine group, the bispectral index at 0, 5, 10 and 15 min was 55 (52-58), 55 (51-59), 55 (52-59) and 56 (53-59), respectively. In the diltiazem group, values were 59 (48-71), 60 (51-70), 61 (52-71) and 61 (50-72), respectively. Both L-type Ca2+ channel blocking agents significantly decreased arterial pressure. CONCLUSIONS: Clinical doses of nicardipine and diltiazem do not alter the bispectral index during general anaesthesia.

Adult↗

Unilateral spatial neglect associated with chronic subdural haematoma: a case report.

A 69-year-old right-handed man who exhibited unilateral spatial neglect in association with a chronic subdural haematoma, presented with mild left arm and leg weakness first noted 4 weeks prior to admission. Neurologic examination on admission revealed a mild left hemiparesis, including the face. Neuropsychologic examination revealed left unilateral spatial neglect, but no language disturbance. Minimal support was necessary to maintain activities of daily living. Computed tomography revealed a large right temporoparietal, extraaxial hypodense fluid collection containing scattered hypodense foci. The haematoma was evacuated via a right parietal burr hole. Following surgery, the patient dramatically improved neurologically and neuropsychologically, as well as in independent performance of daily activities. It is suggested that the improvement in ADL provides a behavioural correlate of improvement in the latter, represented a behavioural correlate of improved cerebral function, and that either direct compression by the chronic subdural haematoma or an interhemispheric pressure difference had caused unilateral spatial neglect. Such neglect is an unusual consequence of chronic subdural haematoma.

Activities of Daily Living↗

Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses.

BACKGROUND: In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia. METHODS: The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n = 39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n = 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18-24 and 20-26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines. RESULTS: Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20-30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30-50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01). CONCLUSION: Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery.

Abdomen↗

Origin of Ca2+ necessary for carbachol-induced contraction in longitudinal muscle of the proximal colon of rats.

The origin of Ca2+ necessary for carbachol (CCh)-induced contraction of longitudinal muscle of the proximal colon of rats was studied. CCh induced contraction of the muscle consisting of two phases, phasic and tonic phases, with a concomitant biphasic increase in [Ca2+]i. After removal of Ca2+ from the bathing solution of the colonic segments, CCh-induced contraction was rapidly inhibited; there was almost complete inhibition 1 min after the removal. Nicardipine, a blocker of voltage-dependent calcium channel, also significantly inhibited CCh-induced contraction. On the other hand, treatment of the colonic segments with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, did not significantly affect the contraction except causing a slight decrease in the rate of contraction. These results suggest that Ca> entering through voltage-dependent calcium channels, but not released from SR, is essential for CCh-induced contraction of longitudinal muscle of the proximal colon of rats. This strict dependency of the CCh-induced contraction on extracellular Ca2+ was discussed in relation to the results obtained in the fundus of rats.

Aminobenzoates↗

[Changes in serum malondialdehyde-modified low-density lipoprotein in patients with acute myocardial infarction and stable angina pectoris treated by coronary angioplasty].

OBJECTIVES: Serum malondialdehyde-modified low-density lipoprotein(MDA-LDL) was measured as a marker of oxidative stress, and the changes in serum MDA-LDL compared in patients with acute myocardial infarction and stable angina pectoris treated by percutaneous transluminal coronary angioplasty (PTCA). METHODS: Forty-one patients with acute myocardial infarction or stable angina pectoris were admitted to our hospitals between January 2000 and June 2000. Direct PTCA was performed in 17 patients(MI group) and elective PTCA in 24 patients(AP group). Coronary angiography was performed in nine control subjects(control group). Serum MDA-LDL was measured in the peripheral venous blood before and immediately after procedures in each group(normal range 20-80 U/l). RESULTS: There were no significant differences in patient characteristics, except age, between the MI group and AP group. Serum MDA-LDL was elevated above the normal range before the procedure in both groups(MI group 104.7 +/- 52.0 U/l, AP group 99.7 +/- 42.8 U/l), and significantly decreased immediately after the procedure(MI group 61.3 +/- 25.6 U/l, AP group 62.0 +/- 29.6 U/l), but there were no significant differences between the two groups. Serum MDA-LDL was elevated before the procedure (99.3 +/- 48.9 U/l) in the control group and significantly decreased immediately after the procedure(61.7 +/- 26.2 U/l). However, these values did not differ from the values before and immediately after the procedure in the MI group and the AP group. The percentage changes in serum MDA-LDL before and immediately after the procedure were -38 +/- 16% in the MI group, -37 +/- 17% in the AP group and -36 +/- 20% in the control group, and there were no significant differences between the three groups. CONCLUSIONS: No significant difference in the changes in serum MDA-LDL was observed between patients with acute myocardial infarction and stable angina pectoris treated by PTCA. However, anticoagulants may affect the MDA-LDL measurements directly, because similar changes in serum MDA-LDL were observed in control subjects after only coronary angiography.

Age Factors↗

Co-induction of heme oxygenase-1 and peroxiredoxin I in astrocytes and microglia around hemorrhagic region in the rat brain.

Heme[none1] oxygenase-1 (HO-1) and peroxiredoxin I (PrxI) are known to be oxidative stress- and heme-related proteins. The antioxidant activity of PrxI is inhibited by heme, therefore co-expression of HO-1 and PrxI is considered to be a reasonable mechanism to maintain its antioxidative function. Immunoblotting demonstrated that HO-1 and PrxI were induced around the hemorrhagic region. Immunohistochemical studies revealed that, in acute phase, HO-1 and PrxI were induced primarily in microglia. In the subacute and chronic phase, the immunoreactivity of HO-1 and PrxI in astrocytes was the most intense. These data are the first to demonstrate co-induction of HO-1 and PrxI in the brain. Our results suggest that HO-1 and PrxI are localized in a similar manner to assure the antioxidant activity of PrxI under stress conditions associated with intracerebral hemorrhage.

Animals↗

Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.

The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.

Anesthetics↗

Oxidative stress-related proteins A170 and heme oxygenase-1 are differently induced in the rat cerebellum under kainate-mediated excitotoxicity.

A170 and heme oxygenase-1 (HO-1) are characterized as oxidative stress-inducible proteins whose induction depends upon common transcription factor via antioxidant responsive element. We investigated the expression of A170 and HO-1 in the cerebellum after kainate administration. In situ hybridization showed constitutive expression of A170 and HO-1 mRNA in Purkinje cell layer; mild induction of A170 or HO-1 was detected, respectively, 8 or 24 h after kainate administration. Immunohistochemical studies also demonstrated that constitutive expression and the induction of A170 protein in Purkinje cells; the induction of HO-1 protein was detected in Bergmann glia but not in Purkinje cells. Thus, the transcription factors involved in the induction of A170 might be different from those in the induction of HO-1 under kainate-mediated excitotoxicity. The existence of cell type-specific stress response was suggested.

Animals↗

Simultaneous kindling of the bilateral hippocampi: an advanced model for epilepsy research.

PURPOSE: To examine whether simultaneous kindling of bilateral hippocampi [bilateral kindling (BK)] could accelerate the achievement of seizures by the breakdown of kindling antagonism or decelerate the achievement of seizures by its enhancement. METHODS: The hippocampi of 17 adult rabbits were simultaneously kindled bilaterally according to Goddard's method. RESULTS: All animals developed stage 5 convulsions after a mean of 28 stimulations. Six animals showed spontaneous seizure discharges. Afterdischarge duration increased abruptly during the early period of kindling, but thereafter it gradually progressed. Chronological analyses of interictal discharges (IIDs) demonstrated that simple as well as complex types of IIDs increased their frequencies during BK. CONCLUSIONS: Compared with unilaterally kindled animals, the BK procedure significantly increased the percentage of animals that successfully kindled (100% vs. 59%; p < 0.01), whereas it significantly decelerated the kindling progression (28 days vs. 19 days; p < 0.02). We conclude that the BK procedure represents potentiation of both excitatory and inhibitory mechanisms. Although the reason why such an antagonistic relationship between them breaks down is still unknown, the BK provides an advanced animal model to study the pathogenic mechanisms of kindling and to screen anticonvulsants.

Animals↗

[Manifestation of primary biliary cirrhosis and Basedow's disease caused by exposure to carbon monoxide in a patient with HTLV-1 associated myelopathy].

A 55-year-old woman with HTLV-1 associated myelopathy (HAM) was discovered in a rentan kotatsu (Japanese foot warmer with a frame and a coverlet by burning briquet) with conscious disorder and admitted to an emergency hospital. Her conscious disturbance waned the 3rd day after admission with gradual improvement of communication and food intake. However, on the 18th day after admission, her orientation was poor again and she was unable to take food for herself and keep sitting. She was diagnosed as suffering from an interval form of acute carbon monoxide (CMO) poisoning and transferred to our hospital for the purpose of hyperbaric oxygen therapy on the 20th day after exposure to CMO. In the course of treatment she recovered but showed jaundice, pruritus, liver dysfunction and elevation of antimitochondrial antibody. She received liver biopsy and was found to have primary biliary cirrhosis (PBC). On the 150th day, she manifested perspiration and hypertension. The clinical and immunological feature revealed her Basedow's disease. The relationship between HAM and PBC due to the autoimmune process has been predicted by investigators. The implication of autoimmune disease and HLA haplotype is a main focus of attention. Our case supports their hypothesis, and suggested that the complication occurred with immunological and genetic correlation. Anti-HTLV-1 antibody was positive at a titer of 1:8192 before exposure to CMO. On transferring to us, it was negative and revealed excessive positive at a titer of 1:20,480 on the 80th day. Immunoglobulin analysis was normal on admission and increased during hospitalization. It was reported that prenatal exposure to relatively mild concentrations of CMO in rats reduces splenic macrophage phagocytosis and killing ability as well as macrophage respiratory burst. These data suggested that PBC and Basedow's disease were manifested by exposure to carbon monoxide.

Acute Disease↗

Effects of kainate-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain.

Stress proteins play important roles in the protective mechanisms under critical conditions for cell survival. We report here the expression of A170 and MSP23, oxidative stress-inducible proteins, under kainate-mediated excitotoxicity in the rat brain. A170 mRNA was significantly induced in the brain 5-8 h after i.p. kainate administration. MSP23 mRNA was observed at quite a low level in the rat brain, and the induction of MSP23 mRNA was not observed during the period 24 h after kainate administration. Immunoblot analysis demonstrated that the maximal expression level of A170 protein occurred 8 h after treatment in each part of the brain. MSP23 protein was constitutively expressed in the brain and the level of this protein was significantly decreased during the period 24 h after kainate administration. In situ hybridization and immunohistochemical studies showed that A170 was expressed predominantly in neurons, especially in pyramidal neurons of the cerebrum and cerebellar Purkinje cells, while MSP23 was expressed in oligodendrocytes. The induction of A170 was observed in the regions which are affected by excitotoxicity and this induction was observed in the earlier phase than cell death. Also, the region which shows high vulnerability to excitotoxicity such as pyramidal cell layer in the hippocampus, showed lower A170 expression than that which shows resistance to excitotoxicity, such as the dentate gyrus in the hippocampus. These results suggest that A170 may play a protective role in the brain under kainate-mediated excitotoxicity.

Animals↗

Induction of heme oxygenase-1 in the rat brain by kainic acid-mediated excitotoxicity: the dissociation of mRNA and protein expression in hippocampus.

Heme oxygenase-1 (HO-1) is induced under various stresses. Here we report the induction and localization of HO-1 in the rat brain by intraperitoneal administration of kainic acid (KA). Both mRNA and protein of HO-1 were markedly induced by KA treatment, and each maximal induction was observed 24 h after KA administration. In situ hybridization analysis showed that HO-1 mRNA appeared predominantly in glial cells, and confined neurons were positive in the cerebral cortex, basal ganglia, and hippocampal pyramidal cell layer. Immunohistochemical analysis showed that the positive cells in the cerebral cortex and hippocampus were mainly astrocytes and microglia, whereas neurons in the basal ganglia showed intense immunoreactivity. We also demonstrate the dissociation between HO-1 mRNA and protein level in the hippocampal pyramidal neurons, which is known to be vulnerable against excitotoxicity, and discuss the correlation between this dissociation and the vulnerability of hippocampal pyramidal neurons.

Animals↗

Short-term and long-term effects of low-density lipoprotein (LDL) apheresis on restenosis after percutaneous transluminal coronary angioplasty (PTCA): is lowering Lp(a) by LDL apheresis effective on restenosis after PTCA?

It has been reported that serum lipoprotein(a) (Lp[a]) levels in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) were significantly higher than in patients without restenosis. In this study, we evaluated the preventive effect of LDL apheresis on restenosis after PTCA in patients with hypercholesterolemia. For 10 patients who had shown a serum cholesterol level of more than 220 mg/dl despite treatment with antihypercholesterolemic drugs, LDL apheresis was conducted every 2 weeks after a successful PTCA until restenosis could be checked. In 4 patients, LDL apheresis was conducted for 2 years. LDL apheresis significantly reduced serum cholesterol from 248 +/- 22 mg/dl to 135 +/- 26 mg/dl and Lp(a) from 42 +/- 34 mg/dl to 21 +/- 16 mg/dl. The average degree of stenosis in the 11 lesions undergoing PTCA was 92 +/- 6% before PTCA, 35 +/- 10% immediately after PTCA, and 38 +/- 19% at 3 to 4 months after PTCA. Restenosis was observed in only 1 lesion. In 4 patients who received LDL apheresis for 2 years, restenosis did not occur in any of the 4 lesions treated. We concluded that LDL apheresis was an efficacious therapy to prevent restenosis after PTCA in patients with hypercholesterolemia.

Adult↗

Physicochemical properties of calcium polycarbophil, a water-absorbing polymer.

The physicochemical properties of calcium polycarbophil were examined. Calcium polycarbophil was decalcified rapidly under acidic conditions, affording polycarbophil. Polycarbophil absorbed about 10 times its own weight of water under acidic conditions, but the swelling ratio markedly increased at above pH 4.0 and reached 70 times the initial weight under neutral conditions. The swelling of polycarbophil was not affected by non-ionic osmolarity, but was affected by ionic strength, showing a decrease with increase of ionic strength. Monovalent metal ions such as sodium and potassium ions in gastrointestinal fluid did not reduce the equilibrium swelling of polycarbophil, but divalent ions such as calcium and magnesium ions did. However, calcium ion only slightly reduced the equilibrium swelling under sodium-rich conditions. The viscosity (as an indicator of fluidity) of polycarbophil was larger than that of CMC-Na at every shear rate and polymer content examined.

Acrylic Resins↗