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Biomedical subjects

H Hashiguchi

Publications and source records attributed to H Hashiguchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Methamphetamine induces fos expression in the striatum and the substantia nigra pars reticulata in a rat model of Parkinson's disease.

In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion in the nigrostriatal pathway, methamphetamine (3 mg/kg, i.p.) induced Fos-like immunoreactivity (FLI) not only in the striatum on the intact side but also in the substantia nigra pars reticulata (SNr) on the lesioned side. The methamphetamine-induced hyperexpression of FLI in the SNr on the lesioned side was suppressed by pretreatment with either dopamine D1 receptor antagonist SCH-23390 (0.5 mg/kg, i.p.), D2 receptor antagonist raclopride (2 mg/kg, i.p.) or N-methyl-d-aspartate receptor antagonist MK-801 (1 mg/kg, i.p.), which was concomitant with inhibition of the methamphetamine-induced rotational behavior of each antagonist. However, the hyperexpression of FLI in the SNr was not suppressed by intrastriatal grafts of fetal ventral mesencephalon which could suppress the methamphetamine-induced rotation completely. These results indicate that opposite hemispheric asymmetries in FLI are induced by methamphetamine in the striatum and the SNr in the 6-OHDA rats. It is suggested that the FLIs in the two discrete sites are activated independently by different mechanisms, and furthermore, different neuronal pathways are involved in the methamphetamine-induced rotation and Fos expression in the SNr of 6-OHDA rats.

Animals↗
PubMed1998

Peripherally administered tetrahydrobiopterin increases in vivo tryptophan hydroxylase activity in the striatum after transplantation of fetal ventral mesencephalon in six hydroxydopamine lesioned rats.

The intraperitoneal administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a natural cofactor for tyrosine hydroxylase and tryptophan hydroxylase (TRH), dose-dependently increased the extracellular concentration of 6R-BH4 itself in rat striatum. The concentration was investigated by in vivo microdialysis and measured simultaneously with 5-hydroxytryptophan (5-HTP), a precursor of serotonin, by high performance liquid chromatography with electrochemical detection. The 6R-BH4 (50 mg/kg, i.p.) administration increased the accumulation of 5-HTP as an index of in vivo TRH activity under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 in the striatum of both normal control and 6-hydroxydopamine lesioned rats with intrastriatal transplants of fetal ventral mesencephalon (VM). The results suggest that TRH in the striatum of both control and VM-grafted rats is activated by 6R-BH4 penetrating into the brain from the blood.

5-Hydroxytryptophan↗
PubMed1998

Nuclear pore changes and absence of apoptosis in lumbar dorsal root ganglion neurons of doxorubicin-intoxicated rats.

Doxorubicin (DXR) produces degeneration of neurons in the lumbar dorsal root ganglion (DRG) in rats. Light microscopic studies, which included the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method, and electron microscopic observation revealed that the moderate nuclear and remarkable cytoplasmic degeneration of DRG neurons of Sprague-Dawley rats after intravenous administration of 8 mg/kg of DXR was cell necrosis, not apoptosis. In some neurons, mostly dark and usually with moderate degrees of nuclear degenerative changes, the nuclear pores were decreased in number and obscure 14 and 20 days after DXR administration. DXR enters presumably the nucleus and is partly removed through the nuclear pores. However, the diameters of nuclear pores were similar in DXR-intoxicated and control rats. The changes in nuclear pores of neurons in DXR intoxication, which to our knowledge has not been previously studied, are considered to be part of the degenerative or necrotic changes of DRG neurons.

Animals↗
PubMed1998

Serotonergic activity in the rat striatum after intrastriatal transplantation of fetal nigra as measured by microdialysis.

In vivo microdialysis was used to examine the effects of dopaminergic transplants on extracellular concentrations of dopamine (DA), serotonin (5-HT), and their precursors and major metabolites in the denervated rat striatum. Dialysis perfusates were collected from intact 6-hydroxydopamine (6-OHDA) lesion plus sham grafted, and lesion plus fetal substantia nigra (SN) grafted striata. The SN transplants ameliorated the reduction of striatal DA and dihydroxyphenylacetic acid (DOPAC) levels in rats with unilateral 6-OHDA lesions of the mesostriatal pathway. The transplants also increased extracellular levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the denervated striatum. In response to NSD-1015 (an inhibitor of aromatic L-amino acid decarboxylase, AADC), 5-hydroxytryptophan (5-HTP) levels were substantially elevated in the SN grafted striata as compared with those in the sham grafted controls, which continued even after subsequent administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100 mg/kg i.p.). Immunohistochemical analysis showed hyperinnervation of 5-HT fibers in the grafted striatum, which was consistent with the results of microdialysis experiments. These results indicated that implantation of SN grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of 5-HT synthesis, release and metabolism.

5-Hydroxytryptophan↗
PubMed1997

Single and repeated environmental stress: effect on plasma oxytocin, corticosterone, catecholamines, and behavior.

Rat studies were done to further characterize an environmental model of stress designated shaker stress (SS). Plasma oxytocin (OT), corticosterone (CS), norepinephrine (NE), and epinephrine (E) were measured before and after 5 or 30 min of SS applied one time or applied 10 times over a 2-week period. The major findings were partial adaptation of plasma E within 30 min of acute SS, adaptation of plasma CS baselines but not responses to chronic SS, and complete adaptation of plasma OT responses to chronic SS. Poststress behavior during chronic SS was affected in the following ways: freezing time habituated, defecation and rearings increased, and grooming and teeth chattering remained relatively constant. The results show that SS produces consistent patterns of hormonal and behavioral responses; some aspects of the patterns are similar to those elicited by other environmental stresses, whereas some aspects are unique to SS. We conclude that rats do not adapt to repeated SS but rather that most hormonal and behavioral defense mechanisms are renewable on a daily basis.

Animals↗
PubMed1997

Central nitric oxide donors attenuate cardiovascular and central norepinephrine responses to stress.

An earlier study showed that norepinephrine (NE) was released in the paraventricular nucleus (PVN) and posterior hypothalamus (PH) along with increases of mean arterial pressure (MAP) and heart rate (HR) during shaker stress (SS). Here we investigated the possibility that nitric oxide (NO) donors, infused into hypothalamus, could modulate responses to SS. In conscious rats, an injector-microdialysis probe, for direct application of donor and collection of extracellular NE, respectively, was inserted into PVN or PH; MAP and HR were recorded continuously from conscious rats. The NO donor, molsidomine (Mol), infused 5 or 30 min before SS, did not alter baseline values of NE, MAP, or HR, but did attenuate changes elicited by 5 min of SS; methylene blue blocked the effects of Mol. The NO donor, sodium nitroprusside, was much less effective than Mol as a modulator of stress-related effects. The results indicate that MAP, HR, and hypothalamic NE responses to environmental stress, but not baseline values, can be modulated by NO donors in the hypothalamus.

Animals↗
PubMed1996

Dopaminergic transplants suppress L-DOPA-induced Fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease.

We examined the effects of MK-801, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and fetal ventral mesencephalic (VM) transplants on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced Fos protein expression in the dopamine (DA)-depleted striatum. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were produced in young adult female rats and grafting was performed 3 weeks later. Methamphetamine-induced rotational behavior recovered significantly on the 4th week after grafting. Immunohistochemical examinations of c-Fos and tyrosine hydroxylase (TH) were performed 3-4 months after grafting. L-DOPA (100 mg/kg, i.p.) markedly induced Fos-like immunoreactivity (FLI) in the DA-depleted striatum. Pretreatment with a large dose of MK-801 (3-4.5 mg/kg, i.p.) dose-dependently suppressed L-DOPA-induced FLI in the striatum. The stimulatory effect of L-DOPA on c-Fos expression observed within the lesioned striatum was suppressed by fetal VM transplants. It seemed that the graft-induced effect on FLI extended over a considerably larger area than that covered by the graft-derived TH-immunoreactive innervation. Taken together, these findings suggest that glutamatergic modulation is involved in the L-DOPA-induced c-Fos expression in the denervated striatum which is normalized by fetal VM transplants. It also seems likely that VM grafts suppress the L-DOPA-induced expression of transcriptional factors which might be involved in the mechanisms underlying various side effects of chronic L-DOPA therapy.

Animals↗
PubMed1996

Dopaminergic transplants alter in vivo activity of tryptophan hydroxylase in the striatum in a rat model of Parkinson's disease.

L-3,4-Dihydroxyphenylalanine (L-DOPA) inhibits the activity of tryptophan hydroxylase (TRH) and thus serotonin synthesis. This inhibitory effect of L-DOPA may be related to some side effects in the patients under L-DOPA therapy. The effects of transplantation of fetal ventral mesencephalon (VM) on extracellular 5-hydroxytryptophan (5-HTP) accumulation was examined by microdialysis as an index of in vivo activity of TRH in the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the rat striatum perfused with m-hydroxybenzylhydrazine (NSD-1015; an inhibitor of aromatic L-amino acid decarboxylase), L-DOPA and 5-HTP in dialysate were measured simultaneously. In response to NSD-1015, 5-HTP levels were substantially elevated in the lesion plus VM-grafted striata as compared with those in the lesion plus sham-grafted striata. The results indicate that implantation of dopamine-rich VM grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of TRH.

Adrenergic Agents↗
PubMed1993

Selective release of serotonin by endogenous alkaloids, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines, (R)- and (S)salsolinol, in the rat striatum; in vivo microdialysis study.

Dopamine-derived 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines, (R)- and (S)salsolinol, released an enormous amount of serotonin in the rat striatum; the concentration of serotonin increased from undetectable level to 2.53 +/- 0.12 and 3.69 +/- 0.01 microM after perfusion of (R)- and (S)salsolinol, respectively. Salsolinols increased extracellular dopamine level, but to a much lesser degree than serotonin. Other naturally occurring isoquinolines with catechol structure released serotonin and dopamine, but salsolinols were the most potent and selective releaser of serotonin. Serotonin release by salsolinols may be involved in some psychiatric symptoms in L-DOPA therapy or alcoholism.

Alkaloids↗
PubMed1993

[Biomechanical properties of the acromioclavicular joints].

The purpose of this study was to investigate the biomechanical properties of the cartilagenous element of the acromioclavicular joint. Experimental specimens of the distal end of the clavicle were selected from operative excisions from patients with acromioclavicular joint dislocation. Dynamic stiffness, tan delta, cartilagenous thickness, elastic modulus and creep modulus were measured with a Biomechanical Spectrometer. The results were as follows: There was a negative correlation between age and values of dynamic stiffness as well as between age and the values of elastic modulus. The values of dynamic stiffness, tan delta, cartilagenous thickness, elastic modulus and creep modulus correlated significantly with the number of days after injury. The values for the anterior parts, excluding dynamic stiffness, were markedly higher than those for the other parts. Aging of the articular cartilage may be a factor in the lowering of dynamic stiffness and elastic modulus. Degenerative change is evidenced by a decrease in cartilaginous thickness and a softening of the articular cartilage. The anterior part of the articular surface showed good load-relaxation and viscoelastic properties. The anterior parts may act as the center of the rotational axis of the clavicle and the fulcrum of the horizontal adduction of the scapula when the arm is raised.

Acromioclavicular Joint↗
PubMed1992

An autopsied case of interferon encephalopathy.

A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organic brain syndrome such as dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed diffuse white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptably severe IFN neurotoxicity.

Aged↗
PubMed1992

[Prevention of stomatitis in patients with acute myelogenous leukemia using PVP-iodine (Isodine) gargle].

From November 1987 to October 1990, we investigated the efficacy of povidine iodine gargle solution (Isodine Gargle) for preventing stomatitis in 26 patients (19 males and 7 females; mean age 53.2 years) with acute myelogenous leukemia (AML). The patients were given a concentrated preparation of the gargle solution which they had to dilute 50 times, and were asked to use it 8 times/day for one year. Twenty patients (76.9%) frequently suffered from stomatitis despite the gargling. Therefore, in the second year they were instructed to use the gargle solution at a higher concentration (30-fold dilution). On the third year, they were asked to increase the frequency of gargling to 10 times/day; this resulted in a significant decrease in frequency of the episodes of stomatitis. Severe and painful stomatitis no longer occurred. Gargling with povidine iodine gargle solution was thus considered effective for preventing stomatitis in AML patients.

Adult↗
PubMed1991

Effect of intra-amygdala dopaminergic grafts on methamphetamine-induced locomotor activity, extracellular dopamine and dopamine metabolite overflow: a comparison with the effect of intra-accumbens grafts.

The effects of 6-hydroxydopamine lesions of the ventral tegmental area and following intra-amygdala or intra-accumbens dopaminergic (DAergic) grafts on methamphetamine (MAP)-induced locomotor activity were investigated in rats. Intra-accumbens DAergic grafts from rat embryos restored the locomotor hyperactivity response to MAP 5 weeks after grafting, while intra-amygdala grafts did not restore responses by 10 weeks after grafting. Biochemical measurements of extracellular DAergic activity in the amygdala (AMY) by in vivo microdialysis after grafting showed no significant change in the basal levels of dopamine (DA) and partial restoration of metabolite levels. MAP induced an increase of DA efflux and a decrease in dihydroxyphenylacetic acid without a significant change in homovanillic acid, which is the same pattern of response seen in control animals. These biochemical changes are similar to those seen previously after intra-accumbens grafts. The results show that restoration of DAergic activity in the AMY in the presence of DAergic denervation of accumbens does not have an effect on MAP-induced locomotion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

[Fibronectin (FN) concentrations in plasma and cerebrospinal fluid (CSF) from guinea pigs with experimental allergic encephalomyelitis (EAE) induced by myelin basic proteins].

The aim of this study was to ascertain whether the FN concentrations in plasma and in CSF are related to the symptomatic status of EAE induced in guinea pigs by myelin basic protein. Guinea pigs were immunized with myelin basic proteins in Freund's complete adjuvant, and after the appearance of neurological symptoms, the plasmas and CSFs from these animals were individually collected. The FN concentrations in these specimens were determined by a solid-phase inhibitory radioimmunoassay using a rabbit antibody specific for guinea pig FN. In plasmas from EAE induced animals, the average value of FN concentrations was lower than that from control animals, but in CSFs from EAE induced animals the average value was slightly higher than that from control animals. The FN concentration in plasma from individual animals with or without EAE was not related to that in the respective CSF, and no direct correlation between the symptomatic severity of EAE and the FN concentration in CSF from the respective animals was observed. These results indicate that the FN concentrations in CSFs probably increase in association with the induction of EAE in guinea pigs, but the levels are highly variable in individual cases, and that the FN concentration in CSF is not available to use as a consistent indicator for EAE in guinea pigs.

Animals↗
PubMed1988

Gerstmann-Sträussler-Scheinker disease: immunohistological and experimental studies.

The older brother of the patient from whom the Fukuoka-1 strain was isolated was found to have numerous kuru plaques, the main finding common to both siblings. Other clinicopathological features including spongiform change were absent in the older brother. Immunostaining using anti-kuru plaque core protein and anti-beta-protein peptide revealed many kuru plaques and a few senile plaques in the older brother. Experimental transmission of the disease to laboratory animals was successful, using tissues from both siblings, through inoculation of fresh brain homogenates, purified prion protein, and formalin-fixed brain homogenates. Prion protein fractions from the patient's brain shortened the incubation periods and formalin-fixed mouse brains did not lengthen the periods. The disease in the two brothers can be classified as Gerstmann-Sträussler-Scheinker disease, a familial variant of Creutzfeldt-Jakob disease. Gerstmann-Sträussler-Scheinker disease manifests a variety of clinicopathological features. Immunohistological verification of kuru plaques has major diagnostic value in assessing dementia.

Aged↗
PubMed1983

Macroporous hydrogel membranes for a hybrid artificial pancreas. I. Synthesis and chamber fabrication.

We report development of special macroporous semipermeable membranes and diffusion chambers made of polymerized 2-hydroxyethyl methacrylate (pHEMA), synthesized specifically to enclose living insulin-producing pancreatic islet cells for the treatment of diabetes. This material was selected to minimize the fibrotic encapsulation which has limited hybrid artificial pancreas efforts with other membranes, including Millipore and Nuclepore filters. The pore density and pore size distribution were dependent on the ratio of water to HEMA monomer and also on the crosslinker (EGDMA) concentration. A macroporous membrane resulted only when the ratio of water/HEMA monomer was greater than 50%. 125I-insulin permeability was studied in vitro. A technique is also described to fuse the membranes to form diffusion chambers used for implantation into diabetic rats.

Biomechanical Phenomena↗