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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 163 records · Page 9Linked to original sources
PubMed1999

Physiologically based pharmacokinetics of KNI-272, a tripeptide HIV-1 protease inhibitor.

The effects of dose on the pharmacokinetic characteristics of KNI-272 were evaluated in rats after intravenous (iv) administration. The plasma kinetics of KNI-272 were dose-independent within a dose range of 1.0 to 10.0 mg/kg. However, when the dose was increased to 50.0 mg/kg, the area under the plasma concentration-time curve (AUC)/dose significantly increased and the total plasma clearance (Cl(tot)) significantly decreased, possibly due to saturation of hepatic metabolism. On the other hand, the terminal elimination half-life (t(1/2,lambda(z))) was independent of dose. Using biochemical and physiological parameters obtained from in vitro and in vivo studies, we developed a physiologically based pharmacokinetic (PBPK) model for KNI-272 in rats in which concentration-dependent nonlinear hepatic metabolism (Michaelis-Menten type metabolism) was considered. Using this PBPK model, plasma KNI-272 concentration-time profiles were simulated. From these profiles it was demonstrated that the terminal elimination phase was proportional to the dose at lower doses. However, as the dose increased to 50.0 mg/kg, the simulated plasma concentrations at the terminal elimination phase increased more than the increase of dose in the same way as the observed data. Accordingly, the dose-dependent plasma kinetics observed after a 50.0 mg/kg dose was considered to be attributable in part to concentration-dependent hepatic metabolism in rats.

Animals↗
PubMed1999

Pharmacokinetic interactions between HIV-protease inhibitors in rats.

The interactions of four HIV-protease inhibitors, ritonavir (RIT), saquinavir (SAQ), indinavir (IND) and nelfinavir (NEL), were examined by in vitro metabolic studies using rat liver microsomal fractions. The substrate concentrations employed were 0.75 approximately 12 microM, and the inhibitor concentrations were 2.5 approximately 60 microM. The metabolic clearance rates of SAQ, NEL and IND as determined by V(max)/K(m) were 170.9+/-10.9, 126.0+/-4.4 and 73.0+/-2.0 microL/min/mg protein, respectively. RIT was a potent inhibitor of the other three protease inhibitors, and the inhibition constants (K(i)) were 1.64 microM for SAQ, 0.95 microM for IND and 1. 01 microM for NEL. NEL was the second strongest inhibitor with a K(i) for NEL inhibition of IND metabolism of 2.14 microM. IND was the third strongest inhibitor with K(i)s of 2.76 microM for inhibition of NEL and 3.55 microM for inhibition of SAQ. As SAQ has the highest metabolic clearance rate, the K(i) for the SAQ inhibition of IND metabolism was high, 9.50 microM. Based on these in vitro results, drug interactions between NEL and IND or RIT were studied after oral administration to rats where the dose of each drug was 20 mg/kg. The C(max) and AUC of NEL were increased 3.6- and 8.5-fold by the co-administration with RIT. However, in contrast to co-administration of NEL and RIT, the effect of IND on the pharmacokinetics of NEL was negligible and the t(1/2) of NEL was not significantly increased by IND. Therefore, the combination of NEL and IND is recommended as a combination therapy for AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Pharmacokinetics of cisplatin in analbuminemic rats.

The effect of protein binding on the pharmacokinetics of cisplatin (cis-diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats, which genetically lack albumins, in comparison with normal rats. CDDP was reported to highly bind to serum components, and the major binder was thought to be an albumin. However, there were no significant differences in the serum disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP to analbuminemic rats as compared with normal rats. The total body clearance, Cl(tot), of platinum in normal rats was 48.7+/-22.0 mL h(-1) (5 mg kg(-1)), 55.9+/-4.04 mL h(-1) (10 mg kg(-1)) and 49.0+/-3.57 mL h(-1) (20 mg kg(-1)), whereas Cl(tot) in analbuminemic rats was 52.0+/-8.48 mL h(-1) (5 mg kg(-1)), 62.9+/-10. 8 mL h(-1) (10 mg kg(-1)) and 62.8+/-6.81 mL h(-1) (20 mg kg(-1)). The serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection were higher in both groups of rats who received CDDP than those of pre-dose level. However, there were no significant differences in the renal function tests between analbuminemic rats and normal rats. The binding of CDDP to the serum samples obtained from analbuminemic rats and normal rats was measured by a centrifuging filtration method. The binding percentages were 68.0+/-5.9% (2.0 microg mL(-1)), 56.8+/-4.1% (5.0 microg mL(-1)) and 64.6+/-4.4% (10.0 microg mL(-1)) in analbuminemic rats and 52.9+/-3.5% (2.0 microg mL(-1)), 52.2+/-3.4% (5.0 microg mL(-1)), 56.9+/-1.9% (10.0 microg mL(-1)) in normal rats. Higher binding percentages were obtained in analbuminemic rats than in normal rats. In vitro binding studies under the two incubation conditions (5 min and 2 h) showed that the binding percentages of CDDP to serum proteins were 59.2+/-3.2% (5 min) and 72.3+/-6.5% (2 h) for albumin, 42.3+/-1.9% (5 min) and 39.5+/-2.5% (2 h) for alpha(1)-acid glycoprotein (AAG) and 51.7+/-5.3% (5 min) and 49. 2+/-1.9% (2 h) for gamma-globulin. From these studies, it was elucidated that albumin is not the major ligand in the rat serum and that other proteins also have important roles in the pharmacokinetics of CDDP.

Animals↗
PubMed1999

Prenatally diagnosed cystic neuroblastoma.

An exceedingly rare case of prenatally diagnosed cystic neuroblastoma (NB) is described. Prenatal ultrasonography at 28 weeks' gestation revealed a cystic right suprarenal mass that measured 15 x 17 mm in diameter. The mass increased parallel to fetal size until it was 41 x 44 mm in diameter at 39 weeks' gestation. Magnetic resonance imaging performed prenatally and after delivery showed two different intracystic intensities with fluid levels, suggesting intracystic hemorrhage. The patient underwent a right adrenalectomy at 20 days of age, and the resected tumor was diagnosed as a poorly-differentiated ganglioneuroblastoma. Eight months after surgery, the patient is generally healthy with no evidence of recurrence. We reviewed 25 additional cases of prenatally diagnosed adrenal cystic NB and examined the clinical features of this rare entity.

Adrenal Gland Neoplasms↗
PubMed1999

Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors.

The effects of the mu-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (microg/kg) or via a microdialysis probe placed into the ventral tegmental area or the nucleus accumbens (nmol). The effect of fentanyl given into the nucleus accumbens was blocked by systemic administration of the non-selective opioid receptor antagonist naloxone and by accumbens administration of D-Phe-Cys-Tyr-D-Trp-Om-Thr-Phe-Thr-NH2 (nmol), a mu-opioid receptor antagonist, and naltrindole (nmol), a non-selective delta-opioid receptor antagonist, in a dose-dependent manner. The delta2-opioid receptor antagonist, naltriben (nmol), also blocked the effects of fentanyl, whereas the delta1-opioid receptor antagonist, (E)-7-benzylidenenaltrexone (nmol), was ineffective. When marginally effective doses of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 and naltriben were given simultaneously, the effect of fentanyl was nearly fully blocked; the pretreatment itself had no effect. Administration of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (nmol), the delta1-opioid receptor agonist [D-Pen2,5]-enkephalin (nmol) or the delta2-opioid receptor agonist [D-Ala2,Glu4]-deltorphin (nmol) into the nucleus accumbens enhanced the amount of accumbal dopamine. This study provides evidence that not only activation of delta1- and delta2-opioid receptors, but also activation of mu-opioid receptors in the nucleus accumbens increases the release of accumbal dopamine in freely moving rats. We suggest that the effect of intra-accumbens administration of fentanyl upon accumbal release of dopamine is either due to the simultaneous activation of mu-opioid receptors and delta2-opioid receptors or due to activation of mu-opioid receptors that interact with delta2-opioid receptors in a complex manner.

Analgesics, Opioid↗
PubMed1999

Tongue muscle activity after orthodontic treatment of anterior open bite: a case report.

A case report of a Class I malocclusion with an anterior open bite and bimaxillary dental protrusion was presented. The patient had a tongue thrust swallow and slight lisping. After the treatment, significant adaptation in electromyographic pattern of genioglossus muscle activity during swallowing was determined. However, remarkable change in the electromyographic pattern of the genioglossus muscle did not occur during chewing.

Adult↗
PubMed1999

Three kinds of antibacterial substances from Lentinus edodes (Berk.) Sing. (Shiitake, an edible mushroom).

Three kinds of antibacterial substances were extracted by chloroform, ethylacetate or water from dried Shiitake mushrooms (Lentinus edodes). These substances possess efficient antibacterial activities against Streptococcus spp., Actinomyces spp., Lactobacillus spp., Prevotella spp., and Porphyromonas spp. of oral origin. In contrast, other general bacteria, such as Enterococcus spp., Staphylococcus spp., Escherichia spp., Bacillus spp., and Candida spp. were relatively resistant to these substances. Chloroform extracts had bactericidal activity against both growing and resting bacterial cells of S. mutans and P. intermedia, whereas the other two extracts showed bacteriostatic activity against both growing and resting bacterial cells of S. mutans and resting bacterial cell of P. intermedia. The antibacterial activity of chloroform extracts and ethylacetate extracts were relatively heat-stable. The water extract was heat-labile.

Anti-Bacterial Agents↗
PubMed1999

Further evidence of westernization of dementia prevalence in Nagasaki, Japan, and family recognition.

The present study examined the prevalence of dementia in the Nagasaki Prefecture. The purposes of our investigation were (a) to study the relationship between aging and the prevalence of dementia and the ratio of Alzheimer's disease (AD) to vascular dementia (VD), (b) to understand the features of early-onset dementia as seen in patients from 60 to 65 years, and (c) to examine the recognition of dementia by family members. The subjects of the study, a total of 4,368, were all 60 years old and over and were residing in the three areas of Nagasaki Prefecture at the time of the investigation, August 1995. We adopted a two-stage design. The first-stage questionnaire that we developed was delivered to subjects, and we selected for the second stage those subjects who met the criteria outlined in the Methods section. The second-stage investigation was an interview by community nurses and psychiatrists. The prevalence of dementia in subjects 60 years and over was 6.2% (men: 5.9%; women: 6.8%). The prevalence increased with age. The AD/VD ratio was 1.4, and was similar to the recent trend in Japan in that the ratio has reversed to resemble the western pattern. In regard to the family members' recognition of illness, the higher the severity of dementia, the higher the recognition ratio of family members became. Only half of these subjects were recognized as having dementia by their family members. In conclusion, the westernization of the AD/VD ratio in Japan was proved. There was little study about family recognition of dementia. In this study, it was remarkable that only half of the subjects were recognized as having dementia by their family members.

Aged↗
PubMed1999

Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers.

AIMS: Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials in Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV). Therefore, the influence of the CYP2D6 genotypes on venlafaxine pharmacokinetics was examined in a Japanese population. METHODS: Twelve adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotypes were determined by codon 188C/T, 1934G/A, 2938G/A and 4268G/C mutations using endonuclease tests based on PCR and by Xba I-RFLP analysis. Subjects were categorized into the following 3 groups (n=4 in each group); Group1: CYP2D6*10/*10, *5/*10, Group2: CYP2D6*1/*10, *2/*10 and Group3: CYP2D6*1/*1, CYP2D6*1/*2. Venlafaxine (25 mg, n=6; 37.5 mg, n=6) was administered orally at 09.00 h following an overnight fast. Plasma concentrations of venlafaxine and ODV were monitored by h.p.l.c. for 48 h. RESULTS: The Cmax and AUC of venlafaxine were 184% and 484% higher in the group 1 subjects than in the group 3 subjects, and 101% and 203% higher in the group 1 than in the group 2, respectively. CONCLUSIONS: These results suggest that CYP2D6*10 influences the pharmacokinetics of venlafaxine in a Japanese population.

Adult↗
PubMed1999

Sudden death in school children: role of physical activities and meteorological conditions.

BACKGROUND: This current study is aimed at investigating the effect of physical activities and meteorological conditions on the sudden deaths of children without obvious causes at school. METHODS: The subjects are 76 victims of sudden death at school in the 12 years from 1983 to 1994 in Aichi Prefecture, Japan. The incidence of these sudden deaths is shown by month of the year, day of the week and hour of the day in relation to physical activities and meteorological factors. The analysis of Hayashi's quantitation type II was used for evaluation of the relationship between sudden deaths under the different physical conditions, such as sedentary (at rest or slow walking) or active (running, competitive sports or swimming) conditions, and meteorological or weather factors such as, season of the year, wind-chill factor, atmospheric pressure and relative humidity. RESULTS: Of 76 cases, 21 died suddenly under sedentary physical conditions and 55 under active conditions. The incidence of sudden death was highest from 10.00 to 11.00 h and on Thursday. Sudden death under sedentary conditions was associated with autumn and winter or with winter with high humidity and low atmospheric pressure. Sudden deaths during running were associated with spring with low humidity and high pressure and sudden deaths during competitive sports were associated with dry and cloudy weather. CONCLUSION: Sudden deaths in children at school may be associated with physical activities and meteorological conditions.

Cause of Death↗
PubMed1999

A new modification of anaesthesia mask for fibreoptic intubation in children.

We made a paediatric anaesthesia mask suitable for fibreoptic intubation by modifying a commercially available disposable mask with a ventilation port (Vent port) on a side. We added a large fibreoptic port (FO port, 22 mm in ID) in the middle of the mask to allow the passage of all sizes of paediatric tracheal tubes. This FO port was covered with an elastic rubber membrane to allow air-tight fibrescopic manipulation Fibreoptic intubation was performed safely through the FO port under continuous manual ventilation with anaesthetic gases via a Vent port connected to the breathing circuit. We succeeded in tracheal intubation in several infants and children with difficult airway in less than ten min, mainly via the nasotracheal route. This fibreoptic mask provides a safer technique for fibreoptic intubation in patients with difficult airways, especially in infants and small children.

Anesthesia, Inhalation↗
PubMed1999

Detection of hepatitis B virus DNA in tissues of hepatocellular carcinomas related to hepatitis C virus which are negative for hepatitis B virus surface antigen.

BACKGROUND: Uniform conclusions have not yet been drawn as to the frequency and copy number of hepatitis B virus (HBV) DNA in hepatocellular carcinoma (HCC) tissues from patients who are negative for hepatitis B surface antigen (HBsAg). METHODS: The existence of HBV DNA was investigated with Southern blot hybridization and polymerase chain reaction (PCR) in HCC tissues from 55 patients who were negative for HBsAg and positive for hepatitis C virus antibody (HCVAb). RESULTS: Southern blot hybridization showed that two tissues (4%) contained HBV DNA at a frequency of more than 1 HBV copy per 10 cells. Another 5 tissues were found to be positive for HBV DNA only by PCR analysis but contained less than 3 HBV DNA copies per 10(5) cells. CONCLUSIONS: HCC tissues from patients seronegative for HBsAg and seropositive for HCVAb contain HBV DNA less frequently than has generally been claimed.

Aged↗
PubMed1999

Ubiquitin stress response in postischemic hippocampal neurons under nontolerant and tolerant conditions.

Ubiquitin, an essential protein in nonlysosomal proteolytic system, is expressed after metabolic stress to the cell. The authors investigated stress response of ubiquitin in the hippocampus of the Mongolian gerbil after forebrain ischemia. The level of hippocampal ubiquitin was compared with that under ischemic tolerance induced by ischemic preconditioning. The authors also studied ubiquitin gene expression using in situ hybridization method. Transient ischemia resulted in consumption of free ubiquitin and an increase of multiubiquitin chains. These changes were transient in the hippocampus outside of the CA1 region where neurons survived, whereas it was persistent in the CA1 region where neurons were destined to die after ischemia. Under tolerant condition, subsequent ischemia provoked rapid recovery and further increase of free ubiquitin. The signal of ubiquitin messenger ribonucleic acid was continuously detected after ischemia, not only under tolerant conditions, but without tolerance induced by preconditioning. Thus, ubiquitin stress response takes place, at least at a transcriptional level, in dying CA1 neurons. Under tolerant conditions, however, subsequent ischemia in the CA1 region induces the stress response of ubiquitin up to the translational level, leading to the rapid restoration of protein synthesis and to eventual neuronal survival.

Animals↗
PubMed1999

Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis.

Although Epstein-Barr virus (EBV) has been reported to be present in some 7% of gastric carcinomas, the nature of the background gastric mucosa of carcinoma has not been elucidated. The authors evaluated the degree of gastritis in the background gastric mucosa of EBV-associated gastric carcinoma. EBV was detected using in situ hybridization for EBV-encoded small ribonucleic acid 1 (EBER-1) in carcinoma cells. The authors compared gastritis in surgically resected stomachs with 8 EBER-1-positive and 16 EBER-1-negative gastric carcinomas of a similar histologic type using histologic variables of the Updated Sydney System. All eight lesions of EBER-1-positive gastric carcinomas had intestinal metaplasia in the background. Mild to moderate glandular atrophy was common in both groups. Many of the tested lesions, 87.5% of EBER-1-positive and 62.5% of EBER-1-negative lesions, were located near the mucosal atrophic border. The background gastric mucosa for EBV-associated gastric carcinomas is rich in atrophic changes. EBV-associated gastric carcinomas are located near the mucosal atrophic border.

Gastric Mucosa↗
PubMed1999

Serum ubiquitin levels in patients with alcoholic liver disease.

Serum concentrations of free ubiquitin and multiubiquitin chain as determined by immunoassays were compared between 10 healthy subjects, and 11 patients with alcoholic hepatic fibrosis, 10 with alcoholic cirrhosis, and 6 with viral liver cirrhosis. All measurements of multiubiquitin chains were expressed in terms of a standard multiubiquitin chain reference preparation 1. Serum concentrations (mean +/- SD) of free ubiquitin and multiubiquitin chains were significantly higher in patients with alcoholic cirrhosis (63.5 +/- 33.7 ng/ml and 7.5 +/- 4.6 ng/ml) than in the normal subjects (29.6 +/- 6.6 ng/ml, p < 0.05 and 4.1 +/- 1.7 ng/ml, p < 0.05), and those with alcoholic hepatic fibrosis (34.8 +/- 16.3 ng/ml, p < 0.05 and 3.0 +/- 0.7 ng/ml, p < 0.05) and viral liver cirrhosis (28.8 +/- 7.5 ng/ml, p < 0.05 and 4.2 +/- 1.3 ng/ml, p < 0.05). Serum levels of both forms of ubiquitin in six patients with alcoholic cirrhosis showed a tendency to decline after 3 months of abstinence. In a total of 14 patients with alcoholic liver damage, 11 with brain atrophy had significantly higher serum levels of both ubiquitin forms than did three patients without brain atrophy (p < 0.05). No correlation was seen between serum concentrations of either form of ubiquitin and liver function test results in the patients with alcoholic liver damage. However, serum levels of both forms of ubiquitin levels correlated significantly with cumulative alcohol intake (p < 0.05). A significant correlation (p < 0.05) also was observed between serum levels of multiubiquitin chains and mean corpuscular volume, a marker of alcohol consumption. These results suggest that the serum concentrations of ubiquitin, especially multiubiquitin chain is a good marker for the diagnosis of alcoholic cirrhosis.

Adult↗
PubMed1999

Surgical orthodontic treatment of skeletal Class III malocclusion with anterior disc displacement without reduction (ADNR): a case report.

A female patient with skeletal problems and left temporomandibular joint (TMJ) derangement was treated with an occlusal splint, arthroscopic irrigation, and orthodontic surgery. The left side disc was displaced anteriorly without reduction; and mobility of the left condylar head was restricted. With arthroscopic irrigation, the jaw functions were recovered, but the disc position remained the same. After TMJ therapy, orthodontic and orthognatic surgery treatments were performed to correct the dentofacial deformity. Stable facial esthetics and occlusion devoid of temporomandibular joint disorder (TMD) symptoms were obtained and the patient's progress was monitored over a 5-year period.

Adolescent↗