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Biomedical subjects

H Ikari

Publications and source records attributed to H Ikari.

At least 37 records · Page 2Linked to original sources
PubMed1996

Central administration of a nitric oxide synthase inhibitor impairs spatial memory in spontaneous hypertensive rats.

Nitric oxide is widely recognized as a putative retrograde messenger in the brain. We infused NG-monomethyl-L-arginine (L-NMMA; 25 mg/kg), an inhibitor of nitric oxide synthase (NOS), continuously for a week into the dorsal third ventricle (D3V) of spontaneous hypertensive rate (SHR) by an osmotic infusion pump. Rats administered with L-NMMA showed impaired performance of a radial arm maze task compared with control rats administered with saline. We observed significant reductions of the NOx level in the cerebrospinal fluid (CSF) of the rats administered with L-NMMA, but not in the control rats. Both groups showed no change in systolic blood pressure or serum NOx level. The results provide evidence of a more specific effect of NOS inhibition to the brain independent of alterations in the systemic hemodynamics.

Animals↗
PubMed1996

Starvation reduces norepinephrine activities in both hypothalamus and heart in rats.

Norepinephrine (NE) activities in both hypothalamus and heart were simultaneously assessed in rats after food-deprivation for 2 days. The technique of gas chromatography-mass spectrometry was employed for the analysis of NE and its primary neuronal metabolite, 3,4-dehydroxyphenylethylene glycol (DHPG), and the ratio of DHPG to NE was used as an index of NE activity. Hypothalamic DHPG/NE ratio was significantly decreased by fasting and was completely reversed by a single day of refeeding. These changes in hypothalamic DHPG/NE ratio were parallel to those in cardiac DHPG/NE ratio. Supporting the concept in which hypothalamic NE neurons play an important role in modulating the sympathetic outflow, it is suggested the decrease in hypothalamic NE activity contributes to the reduction in cardiac NE activity during fasting.

Analysis of Variance↗
PubMed1996

[Hypersensitivity in the pupil dilation response to a cholinergic antagonist in patients with Alzheimer's disease and Down's syndrome].

In 1994, Scinto et al. reported hypersensitivity in the pupil-dilation response to topical application of a cholinergic antagonist, tropicamide, in patients with Alzheimer-type dementia. Similar tests on Japanese subjects showed significant differences in pupil response between subjects with Alzheimer-type dementia (under age 70 years) and age-matched controls. The present study included 24 patients with early-onset Alzheimer-type dementia, 29 patients with late-onset Alzheimer-type dementia, 15 healthy controls (all spouse of patients with Alzheimer-type dementia), 9 patients with vascular dementia and 5 patients with Down's syndrome. After adapting to semi-darkness (10 lux), a solution of tropicamide (Midrin-P, Santen Co, Ltd) was instilled into the right eye. Pupil diameters were measured every 5 to 10 min, and the maximum pupil diameter for each eye was used in the data analysis. The solution was diluted until the tropicamide concentration reached 0.01%. Pupil diameters were measured, and differences between baseline and maximum pupil diameter were computed. Among 18 patients with early-onset Alzheimer-type dementia (mean age 63.9 years) the pupils dilated by 1.12 +/- 0.52 mm (mean +/- SD) as compared with 0.20 +/- 0.75 mm in 7 age-matched controls (mean age 57.8 years); this difference was significant (T-test, p < 0.05). Correlations between the degrees of pupillary dilation and the scores on the revised version of Hasegawa's Dementia Scale were not significant. These data suggest that in subjects under 70 years of age, the diagnostic methods described by Scinto et al. can be used to distinguish those with Alzheimer-type dementia from those without dementia, but those methods may not be effective in subjects over 70 years of age.

Adult↗
PubMed1995

Adenovirus-mediated gene transfer of dopamine D2 receptor cDNA into rat striatum.

A robust feature of mammalian aging associated with diminished motor control is the loss of dopamine D2 receptors from the neostriatum. Decline in this neurotransmitter receptor is also observed in neurodegenerative disorders, such as Huntington's disease and late-stage Parkinson's disease. We have constructed a replication-deficient adenoviral vector to transfer rat dopamine D2 receptor cDNA to brain as a possible therapeutic strategy. Using tissue culture cells infected with this vector, we detected dopamine D2 receptor mRNA by Northern analysis and functional receptor protein in membrane preparations as specific binding of the dopamine D2 receptor ligand, [3H]spiperone. In vivo demonstration involved autoradiographic analysis of [3H]spiperone binding in rat striatum following injection of the adenoviral vector. Dopamine D2 receptor expression was amplified markedly above normal concentrations in the injection site, whereas no increased expression was observed in sites receiving control treatments. These results demonstrate the potential of gene therapy using adenoviral vectors to transfer neurotransmitter receptor proteins to the brain to reverse deficiencies in specific neurodegenerative disorders.

Adenoviridae↗
PubMed1995

Maze learning in aged rats is enhanced by phenserine, a novel anticholinesterase.

A new generation of cholinesterase inhibitors is expected to overcome some limitations of the therapeutic use of anticholinesterases. Phenserine is a long-acting and selective inhibitor of acetylcholinesterase with a preferential brain uptake. We have assessed the effects of chronic phenserine tartrate treatment on performance of aged Fischer-344 rats in the 14-unit T-maze. Phenserine (1-3 mg kg-1, i.p.) treatment for 5 days significantly reduced the number of errors made in the Stone maze. Other performance variables were also improved. No side effects were noted across 5 days treatment at doses of 1-2 mg kg-1. Phenserine can therefore improve the performance of aged rats in this complex maze task without producing obvious side effects.

Aging↗
PubMed1994

Rodent models of memory dysfunction in Alzheimer's disease and normal aging: moving beyond the cholinergic hypothesis.

The Stone maze paradigm has been developed for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Results from several studies have demonstrated the involvement of both cholinergic and glutamatergic systems in acquisition performance in this complex maze task. Although results of clinical studies on the cognitive enhancing abilities of cholinomimetics for treatment of memory impairment in Alzheimer's disease have been inconsistent, new classes of cholinesterase inhibitors offer greater potential for therapeutic efficacy. The physostigimine derivative, phenserine, appears to have marked efficacy for improving learning performance of aged rats or of young rats treated with scopolamine in the Stone maze. Declines in markers of glutamatergic neurotransmission in Alzheimer's disease and in normal aging suggest that pharmacological manipulation of this system might also prove beneficial for cognitive enhancement. Treatment with glycine and/or polyamine agonists is suggested as a strategy for activating the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In addition, the use of combined pharmacological activation of cholinergic and glutamatergic systems is suggested. Manipulation of signal transduction events should also be considered as a strategy for cognitive enhancement. The influx of Ca2+ through the channel formed by the NMDA receptor stimulates the production of the oxyradical, nitric oxide (NO*), via the action of nitric oxide synthase (NOS). Compounds that inhibit NOS activity impair acquisition in the Stone maze, suggesting an involvement of NO*. Thus, strategies for inducing NO* production to enhance cognitive performance may be beneficial. Because of the potential neurotoxicity for NO*, this strategy is not straightforward. Although many new directions beyond the cholinergic hypothesis can be suggested, each has its potential benefits which must be weighed against its risks. Nonetheless, an important unifying area for neurobiological research examining mechanisms of normal brain aging and of age-related neuropathology, as observed in Alzheimer's disease, might emerge from the identification of NO* as a simple molecule serving vital physiological functions but representing potential for neurotoxicity.

Aging↗
PubMed1993

[A case of indomethacin-inhibited recurrent periodical attacks of Mollaret's meningitis].

A 65-year-old woman was admitted to our hospital on May 28, 1990, because of recurrent high fever, over 39 degrees C, headache and general fatigue. In June 1988, she suffered the first episode of high fever, headache and general fatigue. Since then, those symptoms attacked her recurrently at intervals of 7 to 10 days. She was admitted to a hospital for two months in 1988. However, the etiology was unclear and treatment, including antibiotics, was not effective. After admission to our hospital, the symptoms of high fever, headache and general fatigue developed suddenly, lasted for 2 to 4 days, then disappeared spontaneously. These symptoms recurred periodically at intervals of 7 to 10 days. Findings of lumbar puncture during the period with severe symptoms revealed a leukocytic pleocytosis (polymorphonuclear neutrophil count: 1,324/3 mm3, mononuclear cell count: 48/3 mm3, without Mollaret cells) increased protein (0.81 g/l) and decreased glucose (0.28 g/l). Cerebrospinal fluid (CSF) examination during the period without symptoms showed a dramatic decrease of pleocytosis (polymorphonuclear neutrophil count: 5/3 mm3, mononuclear cell count: 17/3 mm3, without Mollaret cells) with improved protein (0/64 g/l) and glucose (0.40 g/l). Various examinations revealed no evidence of infection, malignancy, collagen disease, endocrine disease or any disorders in the nervous system. Moreover, bacterial cultures of blood and CSF were negative and a brain CT scan showed no abnormal findings. We diagnosed this case as Mollaret's meningitis and gave 25 mg indomethacin after every meal (75 mg/day). Her symptoms were improved abruptly and the duration of symptoms shortened and symptom-free intervals became longer.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

[The effect of soluble fiber dietary supplement on constipation in 3 patients with dysphagia who suffered from cerebral infarction with special reference to serum diamine oxidase activity].

Dietary supplement with soluble fibers was given to 3 patients with stroke and dysphagia and obtained improved defecation condition. These clinical effects of soluble fibers should reduce the burden of the patients and families. Long-term inaction of the gastrointestinal tract or continuation of supplementary diet without fibers will induce atrophic intestinal mucosa and abnormal intestinal function. The addition of dietary soluble fibers into supplementary diet can improve the atrophy of the intestinal mucosa and the decline in function of the intestine, constipation and meteorism. The serum diamine oxidase activity, which is regarded as a parameter of intestinal mucosal atrophy, increased with the improvement of constipation and meteorism after addition of dietary soluble fibers. We think that dietary soluble fibers are necessary, especially for the patients who have low diamine oxidase activity. The measurement of serum diamine oxidase activity should be an effective method to evaluate intestinal mucosal atrophy and estimate dietary fibers. We selected a supplementary diet, Enrich-SF, which contains Fibaron, a kind of soluble fiber, galactomannan purified from guar, because this canned supplementary diet has only one kind of soluble fiber. Some consider that soluble fibers are fermented to short-chain fatty acids in the intestinal tract, and improve the disordered bacterial flora in the intestine, resulting in more regular intestinal function. Attention should be paid to dietary fibers in cases of long-term tube feeding.

Aged↗
PubMed1993

[Comparison of typical and atypical bronchoplasty for bronchogenic carcinoma].

One-hundred and twenty-eight patients who underwent bronchoplasty for bronchogenic carcinoma from 1969 to 1990 were retrospectively analyzed. Ninety-six patients had upper sleeve lobectomy or upper lobectomy with wedge bronchoplasty (typical procedure) and 32 underwent bronchoplasty with lobectomy other than upper lobes (atypical bronchoplasty). The two groups were statistically similar in preoperative characteristics including sex, age, cell types and stages. In typical group, right upper sleeve lobectomy was performed in 48 patients, left upper sleeve lobectomy in 27, right upper lobectomy with wedge bronchoplasty in 11, left upper lobectomy with wedge bronchoplasty in 7 and sleeve bronchoplasty alone in 2. In atypical group, right middle and lower lobectomy with sleeve bronchoplasty in 10 patients, left lower sleeve lobectomy in 5, right lower lobectomy with wedge bronchoplasty in 4 and others in 13. Postoperative mortality was 5.2% in the typical group and 9.4% in the atypical group. Postoperative respiratory complications occurred in 16 patients (50%) in the patients with the atypical group and in 33 (34.7%) in those with typical group. Three years and 5 years survival rates in the typical group were 46 and 40% and those in the atypical group, 27 and 18%. However, there was no statistical difference in survival between the two groups. In conclusion, atypical bronchoplasty is useful for preserving the lung parenchyma, but, careful perioperative management and surgical technique of bronchoplasty are mandatory.

Adult↗
PubMed1991

Twenty-four-hour canine lung preservation using UW solution.

The left lungs of 14 mongrel dogs were isolated, preserved, and then reperfused for 120 min. Three groups of lungs were investigated: group 1, nonpreserved lungs (control n = 5); group 2, lungs were flushed with UW solution and cold-stored (4-6 degrees C) in the same flush solution for 24 hr (n = 4); and group 3, lungs flushed and cold-stored with modified Euro-Collins' solution for 24 hr (n = 5). Airway pressure (AWP), static lung compliance (Cst), and pulmonary vascular resistance (PVR) 120 min after reperfusion were significantly higher in group 3 compared with the lungs in group 1 and group 2. AWP was 18.7 +/- 3.9 in group 1, 21.1 +/- 3.8 in group 2, and 33.8 +/- 9.2 ml/cmH2O (mean +/- SD) in group 3 (P less than 0.05). Cst was 14.0 +/- 3.5, 10.8 +/- 1.5, and 6.2 +/- 1.2 ml/cmH2O, respectively (P less than 0.01). Pulmonary vascular resistance was 125 +/- 16, 120 +/- 42, and 410 +/- 108 mmHg/L/min (P less than 0.05). We conclude that UW solution is useful for hypothermic canine lung preservation.

Adenosine↗
PubMed1990

Some effects of CNS cholinergic neurons on memory.

The aim of this study is to observe the relationship between the impairment in passive avoidance task induced in rats by the i.p. administration of muscarinic antagonists, scopolamine and methyl-scopolamine, and the change in acetylcholine (ACh) output induced by these drugs. Initially we studied the effects of these drugs on the animals' performance of a step-through passive avoidance task. We then measured the change in ACh levels after administration of these drugs using an in vivo brain dialysis technique. Scopolamine was effective in impairing the performance of the passive avoidance task, while methyl-scopolamine did not have clear effects on the performance of the task. With regard to ACh output, scopolamine increased ACh dose-dependently and methyl-scopolamine also affected ACh release. These data suggest that the accumulation of ACh in the synaptic cleft may be involved in the memory deficit induced by scopolamine.

Acetylcholine↗
PubMed1979

Factor VIII procoagulant activity, factor VIII related antigen and von Willebrand factor in newborn cord blood.

The mean level of factor VIII procoagulant acitivity (VIII:C) and factor VIII related antigen (VIIIR:AG) was normal in 100 newborn cord plasmas, whereas that of von Willebrand factor (VIIIR:WF) activity was slightly lower than normal. On crossed immunoelectrophoresis, 20 of 50 newborn infants had an increased anodal mobility of VIIIR:AG. When the cord plasma showing an abnormal electrophoretic pattern was mixed with normal plasma, two precipitation peaks with a broad base were found. Similar mixing experiments with the abnormal cord plasma and plasma from a patient with atypical von Willebrand's disease did not normalize the electrophoretic mobility of VIIIR:AG. Gel filtration of the cord plasma with an abnormal electrophoretic pattern of VIII:AG, showed that the three activities were all detected at the position corresponding to a molecular weight of about 800 000. The results suggest the presence of qualitative abnormalities of the factor VIII molecule in half of full-term newborn cord plasma.

Adult↗