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Sadako Kuno

Publications and source records attributed to Sadako Kuno.

At least 19 recordsLinked to original sources
PubMed2007

Placebo-controlled, double-blind dose-finding study of entacapone in fluctuating parkinsonian patients.

We conducted a multicenter randomized, placebo-controlled double-blind parallel-group study in Japanese Parkinson's disease (PD) patients with wearing-off motor fluctuations to determine the clinical efficacy and safety of entacapone as an adjunct to concomitant treatment with levodopa and a dopa decarboxylase inhibitor (DCI). We randomized 341 patients to receive entacapone 100 or 200 mg or placebo per dose of levodopa/DCI for 8 weeks. The primary efficacy variable was on time change while awake, determined by patients' diaries. Mean baseline on time in each group was approximately 8 hours. Mean on time change at final assessment was 1.4 hours each for entacapone 100-mg and 200-mg groups and by 0.5 hours for the placebo group (P < 0.05). The two entacapone doses were equally efficacious. Adverse events occurred in 79 patients (69.9%) in placebo, 82 (72.6%) in 100 mg, and 98 (86.0%) in 200 mg. The most common adverse event with entacapone was an increase in dyskinesias. The overall safety profile was satisfactory in both entacapone groups. In conclusion, both entacapone 100 and 200 mg were equally effective in increasing on time of PD patients with wearing-off fluctuations, although the safety and tolerability profile appeared more favorable for the 100-mg dose.

Aged↗
PubMed2006

Dopaminergic mechanisms controlling urethral function in rats.

AIMS: To investigate the role of dopamine receptor subtypes in the control of urethral activity. METHODS: Simultaneous recordings of intravesical and urethral perfusion pressure (UPP) were performed in rats under urethane anesthesia. Changes in coordinated activity of the bladder and urethral sphincter were examined following intravenous (i.v.), intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration of dopamine D1- and D2-like receptor agonists (SKF38393 and quinpirole, respectively) and antagonists (SCH23390 and remoxipride, respectively). RESULTS: Quinpirole (0.03, 0.1, and 0.3 mg/kg i.v.) dose-dependently decreased baseline urethral pressure to 45.33 +/- 5.8, 33.7 +/- 3.3 (P < 0.05, n = 6), and 27.7 +/- 3.3 cm H(2)O (P < 0.05, n = 5) from the control value (46.0 +/- 4.0 cm H(2)O), respectively. i.c.v. injection of quinpirole (1 microg) decreased baseline urethral pressure to 33.6 +/- 5.0 cm H(2)O (P < 0.05, n = 4) from the control value (51.4 +/- 4.9 cm H(2)O) in contrast to the insignificant effects of i.t. administration of the drug (3 microg). The decrement of baseline pressure induced by quinpirole (0.1 mg/kg i.v.) was suppressed by alpha-bungarotoxin (BGT), a neuromuscular blocking agent. SCH23390 (1 and 3 mg/kg, i.v.) dose-dependently decreased the frequency of high frequency oscillation (HFO) of the urethral sphincter. SKF38393 or remoxipride did not have significant effects on any parameters of bladder and urethral activity. CONCLUSIONS: These results indicate that activation of D2-like dopamine receptors at a supraspinal site can suppress activity of the striated muscle urethral sphincter. Thus, decreased urethral resistance induced by D2 dopamine receptor activation might aggravate urge incontinence symptoms often seen in patients with Parkinson's disease (PD).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2006

Resistin concentrations in murine adipose tissue and serum measured by a new enzyme immunoassay.

OBJECTIVE: In an attempt to clarify the conflicting data on resistin mRNA expression and protein analysis by western blotting in adipose tissue and serum, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) for direct measurement of mouse resistin. RESEARCH METHODS AND PROCEDURES: We developed polyclonal antibodies directed to the N (21 to 40) and C (79 to 91) termini of mouse resistin. Then, affinity-purified anti-C-terminal resistin immunoglobin G (IgG) was biotinylated. ELISA was based on the sandwiching of antigen between antibody IgG coated on polystyrene plates and biotinylated antibody IgG. The bound biotinylated antibody was quantified with streptavidin-linked horseradish peroxidase. RESULTS: New ELISA can measure a concentration as low as 0.5 ng/mL of recombinant mouse resistin and is sensitive and specific enough to measure resistin protein in various adipose tissues and in sera. In normal mice, decreases in resistin concentrations in both white adipose tissue and serum were age dependent during 6 to 24 weeks of development. Resistin concentrations were significantly higher in omental adipose tissue in comparison with perirenal and abdominal adipose tissues and were 2- to 5-fold higher in females than males during the growth period. ob/ob mice had significantly lower resistin concentrations than the control mice in both sera and the white adipose tissues, particularly in the omental fat. The treatment by testosterone, but not progesterone or beta-estradiol, in cultured adipocytes reduces resistin protein levels in a dose-dependent manner. DISCUSSION: New sensitive ELISA for mouse resistin clarified that the resistin concentrations in normal mice were markedly elevated in the omental adipose depots as compared with the perirenal and abdominal adipocyte depots and significantly elevated compared with adipose tissues in genetically obese mice.

Adipose Tissue↗
PubMed2005

Neuroprotection and enhanced recovery with edaravone after acute spinal cord injury in rats.

STUDY DESIGN: The effect of edaravone, a novel free radical scavenger, was assessed functionally and histologically using a rat spinal cord contusion model. OBJECTIVE: To investigate the effect of edaravone on neuroprotection after spinal cord injury in rats. SUMMARY OF BACKGROUND DATA: The spinal cord injury results in immediate physical damage (primary injury), followed by a prolonged neural tissue disorder (secondary injury). This secondary injury process has been suggested to be induced by lipid peroxidation. Edaravone has been reported to inhibit lipid peroxidation in cerebral ischemia models. METHODS: Spinal cord injury at the T10 level was induced with a weight drop device (10 g weight, 25 mm height). Edaravone was administered intravenously as a bolus dose of 5 mg/kg at 5 minutes, 24 hours, and 48 hours after injury (edaravone-treated rats). In control rats, nothing was administered. Functional assessment was conducted weekly using the Basso-Beattie-Bresnahan locomotor rating scores. Histologically, a percentage of spared white matter area was calculated. The effects of intravenous administration of edaravone on lipid peroxide formation in rat spinal cord homogenate were examined using the thiobarbituric acid test for malonyldialdehyde production. RESULTS: Six weeks after injury, edaravone-treated rats showed significantly higher motor score and larger spared white matter area than control rats. The administration of edaravone attenuated malonyldialdehyde production in spinal cord homogenate by >45%. CONCLUSION: Edaravone enhanced functional recovery and preserved more spinal cord tissue after spinal cord injury in rats. The attenuation of posttraumatic lipid peroxide formation by edaravone partially contributed to this enhancement.

Acute Disease↗
PubMed2005

Influence of a tumor necrosis factor gene polymorphism in Japanese patients with multiple system atrophy.

We studied promoter region polymorphisms in the tumor necrosis factor (TNF), interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta1 genes in Japanese patients with multiple system atrophy (MSA) (n=122) and normal controls (n=277). The frequency of the TNF-1031C, a high producer allele of TNF, was increased significantly in MSA patients compared with controls (chi2=12.36, P=0.0021, Pc=0.0084). In contrast, there was no difference in the genotype or allele frequency in the other cytokine gene polymorphisms. We also failed to detect any difference in the disease onset between each genotype of the polymorphisms examined. Our findings suggest that TNF might have a toxic effect in MSA.

Adult↗
PubMed2005

Production of NGF, BDNF and GDNF in mouse astrocyte cultures is strongly enhanced by a cerebral vasodilator, ifenprodil.

Ifenprodil, a non-competitive NMDA-receptor antagonist, has been shown to exhibit marked cytoprotective activities in animal models for focal ischemia and Parkinson's disease. To test the hypothesis that the cytoprotective effect is due to the release of neurotrophic factors (NTFs), we examined the effects of ifenprodil on the NTF contents in mouse astrocyte cultures. The results revealed that ifenprodil strongly enhanced the production of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in these cultures. The ifenprodil-induced NGF secretion was found to be partially mediated by the activation of protein kinase C (PKC) and p42/p44 mitogen-activated protein (MAP) kinase cascade pathways. These findings suggest that the cytoprotective effects of ifenprodil are probably attributed to enhanced secretion of these NTFs from astrocytes.

Animals↗
PubMed2005

Glutathione-S-transferase-1 and interleukin-1beta gene polymorphisms in Japanese patients with Parkinson's disease.

We studied genetic polymorphisms in the glutathione-S-transferase-1 (GST-1) gene region and the interleukin-1beta (IL-1beta) promoter region in patients with Parkinson's disease (PD, n = 361), as well as controls (n = 257). Although we have confirmed the previous results, in a larger sample, that the IL-1beta genotype has affected the age at onset of PD patients, no contribution of the GST-1 gene polymorphism was observed in the allele frequency or the onset age of the disease in Japanese persons.

Adult↗
PubMed2005

Brain-derived neurotrophic factor gene polymorphisms in Japanese patients with sporadic Alzheimer's disease, Parkinson's disease, and multiple system atrophy.

We studied two genetic polymorphisms (240C/T and 480G/A) of the brain-derived neurotrophic factor (BDNF) gene in Japanese patients with Alzheimer's disease (AD, n = 172), Parkinson's disease (PD, n = 327), and multiple system atrophy (MSA, n = 122), as well as controls (n = 275). The distribution of the 240 C/T polymorphism was significantly different between AD patients and controls, whereas there was no difference in the genotype of the two polymorphisms between MSA and controls or between PD and controls. Our data suggest that BDNF might play a role in AD.

Aged↗
PubMed2005

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.

Adult↗
PubMed2004

Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation.

The effects of bone marrow stromal cells (BMSCs) on the repair of injured spinal cord and on the behavioral improvement were studied in the rat. The spinal cord was injured by contusion using a weight-drop at the level of T8-9, and the BMSCs from the bone marrow of the same strain were infused into the cerebrospinal fluid (CSF) through the 4th ventricle. BMSCs were conveyed through the CSF to the spinal cord, where most BMSCs attached to the spinal surface although a few invaded the lesion. The BBB score was higher, and the cavity volume was smaller in the rats with transplantation than in the control rats. Transplanted cells gradually decreased in number and disappeared from the spinal cord 3 weeks after injection. The medium supplemented by CSF (250 microl in 3 ml medium) harvested from the rats in which BMSCs had been injected 2 days previously promoted the neurosphere cells to adhere to the culture dish and to spread into the periphery. These results suggest that BMSCs can exert effects by producing some trophic factors into the CSF or by contacting with host spinal tissues on the reduction of cavities and on the improvement of behavioral function in the rat. Considering that BMSCs can be used for autologous transplantation, and that the CSF infusion of transplants imposes a minimal burden on patients, the results of the present study are important and promising for the clinical use of BMSCs in spinal cord injury treatment.

Animals↗
PubMed2004

Effects of pergolide on nocturia in Parkinson's disease: three female cases selected from over 400 patients.

We started the subject screening from over 400 patients with Parkinson's disease using strict selection criteria to identify the patients with nocturia who would allow accurate and efficient evaluation of the pergolide effects. The subjects were confined to female patients to exclude patients with potential prostate hypertrophy. The patients treated with bromocriptine at 7.5-15 mg/day adjunctive to l-dopa were selected to replace bromocriptine with pergolide of the equivalent dosage approved in Japan. The nocturia was defined as having more than two episodes of urination during sleep per night on average. The subjects received the urinary sediment test before and during the study for screening urinary tract infection and the study was discontinued when urinary tract infection was found. As a result, we identified total 11 patients with nocturia and three of those completed the 12-week study of switching dopamine agonist from bromocriptine to pergolide. We observed a decrease in nocturia frequency in all three patients, a decrease in irritative urinary symptoms in two and an improvement of sleep QOL in two. The effect of pergolide on nocturia was independent of improvement of parkinsonian symptoms, suggesting a distinct mechanism from that of anti-parkinsonian effects. Our study also suggests that switching from bromocriptine to pergolide improves nocturia, thereby improving sleep status of patients with Parkinson's disease.

Aged↗
PubMed2004

Cabergoline stimulates synthesis and secretion of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor by mouse astrocytes in primary culture.

Neuroprotection is the primary concern in patients with newly diagnosed Parkinson's disease. The D2/weak D1 dopamine agonist cabergoline elicits neuroprotection by antioxidation and scavenging free radicals, and may protect neurons by up-regulating endogenous neurotrophic factors synthesis in the brain. In primary cultured mouse astrocytes, cabergoline 37 micromol/l immediately elevated concentrations of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor (GDNF) in culture medium, reaching 9.9-, 2.6- and 30-fold, respectively, of control levels at 16 h. Relative mRNA levels were 3.0-, 1.5- and 1.9-fold, respectively, of controls at 3 h. These effects may be mediated partly by the dopamine D2 receptor. Cabergoline may be a good candidate for an inducer of GDNF, which may have neuroprotective and neurorestorative properties in dopaminergic nigral neurons.

Animals↗
PubMed2004

[Parkinson's disease: the disease concept, etiology and diagnostic bases].

Parkinson's disease (PD) is caused by degeneration of nigral dopaminergic neurons. This results in dysfunction of the basal ganglia, thereby exhibiting movement disorders. The four cardinal signs of PD include bradykinesia, rigidity, resting tremor and postural instability. In the majority of patients with PD, the four cardinal signs are ameliorated by levodopa. In addition to anti-parkinson medication, surgery of the basal ganglia for PD has been applied. Local electrical stimulation of particular nuclei of the basal ganglia (deep brain stimulation) for PD has also proved to give satisfactory outcome. Both genetic and environment factors are considered to contribute to the initiation of PD. Some mutations of particular genes (e.g., alpha-synuclein) are found to link to parkinsonian families.

Aged↗
PubMed2004

[Prevention and treatment of malignant syndrome in patients with Parkinson's disease].

This article summarizes the prevention and treatment of malignant syndrome (MS) in Parkinson's disease. MS is often induced by sudden withdrawal of levodopa. However, many other events can be responsible for the induction of MS, including concomitant infections, dehydration, hot weather, discontinuation of other antiparkinsonian drugs, and 'wearing off' phenomenon. MS should be suspected when the body temperature rises above 38 degrees C without an apparent cause. The early detection and its prompt commencement of treatment are essential for improving the prognosis of the disease. The treatment consists of ample intravenous fluid, cooling the body, antiparkinsonian drugs (particularly, levodopa and bromocriptine), dantrolene sodium, and antibiotics if infection is present.

Antiparkinson Agents↗
PubMed2003

Increase of antioxidative potential by tert-butylhydroquinone protects against cell death associated with 6-hydroxydopamine-induced oxidative stress in neuroblastoma SH-SY5Y cells.

Recent findings suggest that oxidative stress caused by dopamine could be closely involved in the pathogenesis of Parkinson's disease (PD). tert-Butylhydroquinone (tBHQ) is known as a strong inducer of phase II detoxification enzymes which have antioxidative functions. In this study, we investigated the neuroprotective effect of tBHQ against 6-hydroxydopamine (6-OHDA)-induced cell death using human neuroblastoma SH-SY5Y cells. The pretreatment of SH-SY5Y cells with tBHQ significantly reduced 6-OHDA-induced generation of reactive oxygen species (ROS), the phosphorylation of c-Jun N-terminal kinase (JNK), and subsequent cell death. We also observed that tBHQ increased the intracellular glutathione levels and induced the expression of NAD(P)H:quinone oxidoreductase (NQO1) mRNA. In addition, tBHQ dose-dependently activated the antioxidant responsive element (ARE), which plays a key role in the transcriptional activation of phase II detoxification enzymes including NQO1. These results indicate that an increase of intracellular antioxidative potential in SH-SY5Y cells by tBHQ treatment protects cells from 6-OHDA-induced oxidative stress.

Antioxidants↗
PubMed2003

Effects of dopamine agonists bromocriptine, pergolide, cabergoline, and SKF-38393 on GDNF, NGF, and BDNF synthesis in cultured mouse astrocytes.

We examined the stimulatory effects of the dopamine agonists bromocriptine, pergolide, cabergoline, and SKF-38393 on the synthesis and secretion of neurotrophic factors (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF; and glial cell line-derived neurotrophic factor, GDNF) in cultured mouse astrocytes, and clarified the role of dopamine D1 and D2 receptors in these effects. Bromocriptine, a D2 agonist, elevated NGF levels in the culture medium 6.8-fold vs. control, and significantly decreased GDNF and BDNF levels, at 24 h. Both pergolide, a D1/D2 agonist, and cabergoline, a D2/weak D1 agonist, rapidly elevated NGF and GDNF levels at 4-6 h, respectively to 21- and 1.5-fold, respectively, and 84- and 9-fold, respectively, of control levels at 24 h. SKF-38393, a D1 agonist, elevated NGF and GDNF levels to 20- and 2.8-fold of controls, respectively, at 24 h. Relative levels of NGF and GDNF mRNA detected by Northern blot analysis or semiquantitative reverse transcriptase-polymerase chain reaction confirmed that increases in levels of the 2 proteins in culture medium were due to overexpression as opposed to leakage from cells. Cabergoline rapidly increased GDNF mRNA expression at 4 h, producing a potent and long-lasting increase in GDNF levels. Bromocriptine significantly suppressed GDNF synthesis. These findings suggest that stimulation of dopamine D1 receptors may be required for GDNF synthesis and secretion, and that concurrent stimulation of dopamine D1 and D2 receptors may augment synthesis and secretion of NGF and GDNF. These dopamine agonists may play a role in neuronal survival by stimulating NGF and GDNF synthesis in the brain, and as drugs are good candidates as NGF and GDNF inducers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

Influence of monocyte chemoattractant protein 1 gene polymorphism on age at onset of sporadic Parkinson's disease.

We studied polymorphisms in the genes for monocyte chemoattractant protein 1 (MCP-1) and CC chemokine receptor (CCR)-2 in 171 Parkinson's disease (PD) patients and 340 controls. Although no associations were found in alleles or genotypes, MCP-1 -2518A/G genotype affected the age-at-onset of PD patients. This effect was also detected in a second PD group, suggesting a possible involvement of MCP-1 in PD.

Adult↗