Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 199 records · Page 11Linked to original sources

PubMed1999

Add-on polytherapy with antidepressants and its significance in inpatients with major depression.

Add-on polytherapy with antidepressant agents was reviewed in 42 inpatients with major depression diagnosed according to the ICD-10 criteria. Twenty-eight (67.7%) patients were treated with two or more antidepressants. The most frequent combination consisted of a tricyclic antidepressant and a non-tricyclic antidepressant. Nineteen (67.8%) patients of the polytherapy group were treated with a dosage equivalent to 150 mg/day of tricyclic antidepressant. Clinically, not every patient with major depression can tolerate the adverse side effects induced by an effective dose of a single tricyclic antidepressant. From this viewpoint, add-on polytherapy with antidepressants could be one of the treatment options, especially for such intolerant patients.

Adult↗

PubMed1999

Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin.

To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non-selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor.

Adenosine↗

PubMed1999

Possible involvement of interleukin-1 in cyclooxygenase-2 induction after spinal cord injury in rats.

A standardized compression injury of rat spinal cord brought about a time-dependent biphasic production of thromboxane A2 (detected as thromboxane B2) and prostaglandin I2 (detected as 6-ketoprostaglandin F1alpha). Thromboxane B2 was predominant during the first 1 h, whereas the 6-ketoprostaglandin F1alpha level exceeded that of thromboxane B2 at 8 h postinjury. As examined by inhibitor experiments and northern blotting, cyclooxygenase-1 was responsible for the first phase, and cyclooxygenase-2 was involved in the second phase. On compression injury the levels of interleukin-1alpha and -1beta detected as mRNA and protein increased and peaked at 2-4 h. Injection of exogenous interleukin-1alpha into the spinal cord resulted in an increase of cyclooxygenase-2 mRNA content and a predominant production of 6-ketoprostaglandin F1alpha resembling the second phase of eicosanoid production. Concomitantly, extravascular migration of polymorphonuclear leukocytes was enhanced after the interleukin-1alpha injection. These cells together with vascular endothelial cells and glial cells were stained positively with an anti-cyclooxygenase-2 antibody. The results suggest that the immediate eicosanoid synthesis after spinal cord injury was due to the constitutive cyclooxygenase-1 and the delayed synthesis of eicosanoids was attributable to the induction of cyclooxygenase-2 mediated by interleukin-1alpha.

Animals↗

PubMed1999

Effects of moderate hypothermia on constitutive and inducible nitric oxide synthase activities after traumatic brain injury in the rat.

We investigated the effects of therapeutic hypothermia (30 degrees C) on alterations in constitutive (cNOS) and inducible (iNOS) nitric oxide synthase activities following traumatic brain injury (TBI). Male Sprague-Dawley rats were anesthetized with 0.5% halothane and underwent moderate (1.8-2.2 atm) parasagittal fluid-percussion (F-P) brain injury. In normothermic rats (37 degrees C) the enzymatic activity of cNOS was significantly increased at 5 min within the injured cerebral cortex compared with contralateral values (286.5+/-68.9% of contralateral value; mean+/-SEM). This rise in nitric oxide synthase activity was significantly reduced with pretraumatic hypothermia (138.8+/-17% of contralateral value; p < 0.05). At 3 and 7 days after normothermic TBI the enzymatic activity of cNOS was decreased significantly (30+/-8.4 and 28.6+/-20.9% of contralateral value, respectively; p < 0.05). However, immediate posttraumatic hypothermia (3 h at 30 degrees C) preserved cNOS activity at 3 and 7 days (69.5+/-23.3 and 78.6+/-7.6% of contralateral value, respectively; mean+/-SEM; p < 0.05). Posttraumatic hypothermia also significantly reduced iNOS activity at 7 days compared with normothermic rats (0.021+/-0.06 and 0.23+/-0.06 pmol/mg of protein/min, respectively; p < 0.05). The present results indicate that hypothermia (a) decreases early cNOS activation after TBI, (b) preserves cNOS activity at later periods, and (c) prevents the delayed induction of iNOS. Temperature-dependent alterations in cNOS and iNOS enzymatic activities may participate in the neuroprotective effect of hypothermia in this TBI model.

Animals↗

PubMed1999

Effects of L-NAME and 7-NI on NOS catalytic activity and behavioral outcome after traumatic brain injury in the rat.

Traumatic brain injury (TBI) produces transient increases in constitutive nitric oxide synthase (cNOS) activity and prolonged behavioral abnormalities. This study investigated the effects of nitro-L-arginine-methyl ester (L-NAME) and 3-bromo-7-nitroindazole (7-NI) treatment on cNOS catalytic activity and sensorimotor behavioral outcome after TBI. Rats underwent moderate (1.8-2.2 atm) parasagittal fluid percussion brain injury (FPI). At 5 min after FPI, cNOS activity was significantly increased within the damaged cerebral cortex of vehicle-treated rats compared to the noninjured contralateral cortex (206.7 +/- 150.5 % of contralateral, p < 0.01). Pretreatment with L-NAME and 7-NI significantly reduced injury-induced cNOS activation (47.7 +/- 42.6 %, p < 0.05, and 96.16 +/- 12.76, p < 0.05, respectively). Pretreatment with L-NAME and 7-NI also inhibited cNOS activity within the contralateral noninjured cerebral cortex compared to vehicle-treated rats (L-NAME 43.7 +/- 12.47%, p < 0.05; 7-NI 36.8 +/- 7.47%, p < 0.05). Furthermore, pretreatment with 7-NI, but not L-NAME, significantly reduced forelimb placing sensorimotor deficits (3.14 +/- 1.07, p < 0.05) at 1 day after TBI compared to vehicle-treated rats (5.38 +/- 0.42). These data indicate that inhibition of injury-induced elevations in neuronal NOS activity has a beneficial effect on neurological outcome after parasagittal FPI brain injury.

Animals↗

PubMed1999

Allyl-containing sulfides in garlic increase uncoupling protein content in brown adipose tissue, and noradrenaline and adrenaline secretion in rats.

The effects of garlic supplementation on triglyceride metabolism were investigated by measurements of the degree of thermogenesis in interscapular brown adipose tissue (IBAT), and noradrenaline and adrenaline secretion in rats fed two types of dietary fat. In Experiment 1, rats were given isoenergetic high-fat diets containing either shortening or lard with or without garlic powder supplementation (8 g/kg of diet). After 28 d feeding, body weight, plasma triglyceride levels and the weights of perirenal adipose tissue and epididymal fat pad were significantly lower in rats fed diets supplemented with garlic powder than in those fed diets without garlic powder. The content of mitochondrial protein and uncoupling protein (UCP) in IBAT, and urinary noradrenaline and adrenaline excretion were significantly greater in rats fed a lard diet with garlic powder than in those fed the same diet without garlic. Other than adrenaline secretion, differences due to garlic were significant in rats fed shortening, also. In Experiment 2, the effects of various allyl-containing sulfides present in garlic on noradrenaline and adrenaline secretion were evaluated. Administration of diallyldisulfide, diallyltrisulfide and alliin, organosulfur compounds present in garlic, significantly increased plasma noradrenaline and adrenaline concentrations, whereas the administration of disulfides without allyl residues, diallylmonosulfide and S-allyl-L-cysteine did not increase adrenaline secretion. These results suggest that in rats, allyl-containing sulfides in garlic enhance thermogenesis by increasing UCP content in IBAT, and noradrenaline and adrenaline secretion.

Adipose Tissue, Brown↗

PubMed1999

Early treatment with a novel inhibitor of lipid peroxidation (LY341122) improves histopathological outcome after moderate fluid percussion brain injury in rats.

OBJECTIVE: Reactive oxygen species are thought to participate in the pathobiology of traumatic brain injury (TBI). This study determined whether treatment with LY341122, a potent inhibitor of lipid peroxidation and an antioxidant, would provide neuroprotection in a rat model of TBI. METHODS: To investigate the efficacy of LY341122 in this parasagittal fluid percussion model (1.8-2.1 atm), the rats received oral administration of LY341122 (100 mg/kg) or vehicle 2 hours before and 4 hours after TBI (each group, n = 7). To investigate the therapeutic window for treatment, rats were treated with LY341122 or vehicle for 20 hours by femoral vein infusion starting at 5 minutes, 30 minutes, or 3 hours after TBI (each group, n = 5). Three days after injury, analysis of contusion volumes and the frequency of damaged cortical neurons was conducted. RESULTS: Oral administration of LY341122 before and after TBI led to a significant reduction in overall contusion volume (3.28 mm3+/-0.75 mm3 [mean +/- standard error of the mean] versus 1.32 mm3 +/- 0.33 mm3; P < 0.05) and also reduced the frequency of damaged cortical neurons (1191.7 +/- 267.1 versus 474.6 +/- 80.2; P < 0.05). In the second experiment, rats treated with LY341122 at 5 minutes or 30 minutes after TBI also demonstrated a significant reduction (P < 0.05) in contusion volume (1.92 mm3 +/- 0.64 mm3 or 1.59 mm3 +/- 0.50 mm3, respectively) compared with vehicle-treated rats (4.32 mm3 +/- 1.15 mm3). A significant reduction in total cortical necrotic neuron counts was also demonstrated in the 5-minute group (2243.8 +/- 265.3 versus 1457.8 +/- 265.3; P < 0.05). In contrast, histopathological outcome was not significantly improved when treatment was delayed until 3 hours after TBI. CONCLUSION: These data reinforce the hypothesis that lipid peroxidation and reactive oxygen species participate in the acute pathogenesis of TBI. Treatment delayed until 3 hours after TBI did not provide significant histopathological protection.

Administration, Oral↗

PubMed1999

Identification and characterization of the UL14 gene product of herpes simplex virus type 2.

The UL14 gene of herpes simplex virus type 2 (HSV-2) is predicted to encode a 219 amino acid protein with a molecular mass of 23 kDa. In this study, the HSV-2 UL14 gene product has been identified by using a rabbit polyclonal antiserum raised against a recombinant 6 x His-UL14 fusion protein expressed in E. coli. The antiserum reacted specifically with 34, 33 and 28 kDa proteins in HSV-2-infected cell lysates and also with a 34 kDa protein produced by in vitro transcription and translation reactions, suggesting that the 34 kDa protein is the primary translation product of the UL14 gene. The protein was synthesized at late times post-infection (p.i.) and was not detectable in the presence of the viral DNA synthesis inhibitor acycloguanosine. Indirect immunofluorescence studies localized the UL14 protein both to the nucleus and to perinuclear regions of the cytoplasm, and the nuclear UL14 protein was found to co-localize with the scaffolding protein ICP35 at 9 h p.i. However, the protein accumulated in a perinuclear region of the cytoplasm at 12 h p.i., while most of the ICP35 protein localized within assemblons in the nucleus. Although no detectable UL14 protein was associated with intracellular capsids isolated in the presence of 0.5 M NaCl, it was detected in purified virions. Furthermore, the UL14 protein expressed alone was detected both in the nucleus and in the cytoplasm at 24 h after transfection, but was mainly localized to the cytoplasm at later times.

Animals↗

PubMed1999

A recessive Arabidopsis mutant that grows photoautotrophically under salt stress shows enhanced active oxygen detoxification.

Mutagenized Arabidopsis seedlings (ecotype Columbia) were screened for the ability to grow photoautotrophically on solid medium containing 200 mM NaCl. A novel mutant line, designated pst1 (for photoautotrophic salt tolerance1), was obtained. There were no significant differences between pst1 and wild-type plants with regard to their ability to induce proline as an osmoregulatory solute. In addition, the content of monovalent cations in pst1 plants grown with or without salt stress was equal to that in the wild type. We observed that light, even at moderate intensities, increased the effects of salt stress on wild-type plants. The pst1 seedlings were nearly 10 times more tolerant to methyl viologen than were wild-type seedlings. We also found that the activities of the active oxygen scavengers superoxide dismutase and ascorbate peroxidase were enhanced significantly in pst1 plants. The pst1 plants also were tolerant to other stresses, such as high light intensity and toxic monovalent cations. The recessive nature of the pst1 mutation indicates that the potential for salt-stress tolerance is blocked in wild-type Arabidopsis.

Adaptation, Physiological↗

PubMed1999

Bilateral oophorectomy in asymptomatic women over 50 years old selected by ovarian cancer screening.

The purpose of this study was to evaluate bilateral oophorectomy in women over 50 years old found to have an adnexal mass using transvaginal ultrasonography (TVS) as a mass screening. With TVS a total of 23,451 women without symptoms were examined for ovarian cancer at annual screening for uterine cervical cancer. Two hundred fifty-eight women over 50 years old persistently had abnormal TVS results and 95 women gave informed consent for surgical tumor removal. In the 95 women operated, 7 malignant ovarian cancers were found. Especially adnexal masses which were thought to be benign were treated by laparoscopic surgery.

Adnexa Uteri↗

PubMed1999

Correlation between respiratory function and airway inflammation in asthma.

BACKGROUND: Eosinophilic airway inflammation is thought to be associated with airflow limitation and airway hyperresponsiveness. METHODS: Spirometry, peak expiratory flow (PEF) measurement, histamine challenge test, and sputum induction with hypertonic saline inhalation were performed in 70 asymptomatic patients with asthma who were treated with bronchodilators or an inhaled corticosteroid (beclomethasone dipropionate, 400-800 microg/day) or both for more than 2 months. The relationships between the sputum eosinophils, respiratory function, and airway responsiveness to histamine were investigated. RESULTS: Induced sputum was obtained from 53 patients. Although significant correlations between sputum eosinophils and forced expiratory volume in 1 s/forced vital capacity x 100% (FEV1%) or maximum expiratory flow at 25% of the forced vital capacity (V25) divided by height (V25/Ht) were observed, no significant correlations were found between sputum eosinophils and percent predicted PEF (%PEF) or airway responsiveness to histamine. Furthermore, airway responsiveness to histamine was not correlated with FEV1%, V25/Ht or %PEF. CONCLUSION: Single-point measurements of FEV1% and V25/Ht but not PEF or airway responsiveness to histamine correlate with the degree of airway inflammation evaluated indirectly with induced sputum.

Adult↗

PubMed1999

[Pharmacology of conivaptan hydrochloride (YM087), a novel vasopressin V1A/V2 receptor antagonist].

Pharmacology of conivaptan hydrochloride (YM087) was investigated in in vitro and in vivo studies. In radioligand binding study, YM087 showed high affinity for both V1A and V2 receptors in animal and human species. Affinity of YM087 for V1A and V2 receptors was comparable to that of vasopressin (AVP). In functional antagonistic activity study, YM087 concentration-dependently inhibited AVP-induced intracellular Ca2+ elevation via human V1A receptors and AVP-stimulated cAMP accumulation via human V2 receptors. Intravenous administration of YM087 dose-dependently inhibited AVP-induced pressor responses and produced a dose-dependent aquaresis in rats and dogs. Oral administration of YM087 showed a potent and long-lasting antagonistic activity on V1A and V2 receptors. YM087 was effective in dogs with heart failure and in heart failure rats with hyponatremia and edema. These results reveal that YM087 is the first orally active V1A/V2 receptor antagonist and suggest that YM087 may be useful in the treatment of congestive heart failure and hyponatremia.

Animals↗

PubMed1999

Allylthiamindisulfide and related compounds enhance thermogenesis with increasing noradrenaline and adrenaline secretion in rats.

The effects of allylthiamindisulfide, an allyl derivative of thiamin, and related compounds on thermogenesis were investigated by measuring noradrenaline and adrenaline secretion and the temperatures of interscapular brown adipose tissue (IBAT) and rectum in rats. In Experiment 1, the effects of the administrations of allylthiamindisulfide and related compounds on noradrenaline and adrenaline secretion were evaluated as compared to thiamin in anesthetized rats. The administration of allylthiamindisulfide significantly increased the plasma concentrations of noradrenaline and adrenaline. These increases were dose dependent, while that of thiamin was not. Four synthetic compounds related to allylthiamindisulfide also increased the plasma adrenaline and noradrenaline concentrations. In Experiment 2, the effects of allylthiamindisulfide on thermogenesis were investigated by the direct measurement of temperatures in the IBAT and rectum in anesthetized rats, and compared to the effects induced by thiamin and diallyldisulfide. The temperatures in the IBAT and rectum were significantly increased by the administration of allylthiamindisulfide and diallyldisulfide, while there was no significant increase as the result of thiamin administration. These results suggest that allylthiamindisulfide and related compounds enhance thermogenesis by increasing noradrenaline and adrenaline secretion in rats.

Adipose Tissue, Brown↗

PubMed1999

[Taxonomy of genus Malassezia: progress and problems].

The genus Malassezia is composed of lipophilic basidiomycetous yeasts which were recently shown to consist of seven species, one lipid-independent species, M. pachydermatis and six lipid-dependent species, M. furfur, M. sympodialis, M. globosa, M. obtusa, M. restricta and M. slooffiae. Based on this classification, we will be able to analyze pathogenicity or relationship between Malassezia-related diseases and each species.

Malassezia↗

PubMed1999