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Biomedical subjects

Y Koike

Publications and source records attributed to Y Koike.

At least 109 records · Page 6Linked to original sources
PubMed1997

A reliable and convenient parameter of the rate of paracetamol absorption to measure gastric emptying rate of liquids.

The rate of paracetamol absorption represents gastric emptying rate (GER) of liquids. Thus, the liquid GER is assessed by conventional pharmacokinetic parameters such as the maximum concentration and the time to maximum concentration after oral administration of paracetamol. However, the conventional parameters are subject not only to the rate but also to the extent of absorption. For the reliable assessment of GER we have proposed a new parameter, the C0.5/C0.25 ratio, for the rate of paracetamol absorption without being affected by the extent of absorption. Of 15 healthy male volunteers, 9 orally received 10 mg/kg of paracetamol with 200 ml of water as the "normal" GER group, and the other 6 took 10 mg/kg of paracetamol with 200 ml of a liquid nutrient (200 kcal/200 ml), which delays GER, as the "delayed" GER group. Blood samples were obtained at t = 0 (pre-dose), 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours (post-dose). In each subject, GER was assessed by the conventional parameters, the C0.5/C0.25 ratio, and the Wagner-Nelson method which provides an accurate estimate of the drug absorption rate. Using the C0.5/C0.25 ratio and the Wagner-Nelson method we could more clearly differentiate the delayed GER group from the normal GER group than by using the conventional parameters. This suggests that the C0.5/C0.25 ratio and the Wagner-Nelson method may be more reliable than the conventional parameters in detecting a delay in GER. Further, it should be noted that the C0.5/C0.25 ratio can be calculated from only 2 blood samples while the Wagner-Nelson method requires repeated blood sampling.

Acetaminophen↗
PubMed1996

Slow negative cortical potential preceding the onset of postural adjustment.

We investigated whether a cortical potential exists, that is similar to the Bereitschaftspotential, preceding postural adjustment followed by voluntary ballistic rising on tiptoe in 10 healthy subjects. On the basis of the electromyogram (EMG) activities of the soleus muscle, the onsets of the premotion silent period (PMSP) and EMG discharge were determined. The negative potentials associated with a voluntary rise-on-tiptoe movement with respect to EMG onset were similar to the readiness potential associated with voluntary foot movement. The slopes of the slow negative potential associated with the PMSP onset were significantly more negative than those of the potential associated with rise-on-tiptoe movement, particularly over the frontal electrode positions. The results suggest that a cortical potential precedes postural adjustment that is followed by voluntary rising on tiptoe.

Adult↗
PubMed1996

Intracranial extension of paranasal sinus mucocele: two case reports.

In two cases intracranial extension of mucoceles of the paranasal sinus was safely removed by intranasal evacuation and drainage of the lesions located in the paranasal sinus. The diagnosis was ascertained in both cases via intranasal approach. In addition, the volume of the intracranial lesions was reduced. This procedure is both effective and a less invasive diagnostic treatment for the lesion.

Adolescent↗
PubMed1996

Suppression of humoral immunity by monoclonal antibody to CD79b, an invariant component of antigen receptors on B lymphocytes.

CD79b is an invariant component of antigen receptors on B lymphocytes. Previous data have suggested that monoclonal antibody (mAb) to CD79b would introduce negative signals into B lymphocytes and suppress humoral immunity. We tested this hypothesis in this study using in vitro assay systems, and revealed that anti-CD79b mAb effectively suppressed the antibody response to a T-cell dependent antigen. The speculated mechanisms for this immunosuppression were: (i) down-modulation of antigen receptors, (ii) inhibition of B lymphocyte differentiation, and (iii) induction of B lymphocyte unresponsiveness. Of these three, we confirmed that the first two were actually induced by anti-CD79b mAb treatment, whereas the in vitro system could not induce the unresponsiveness of B lymphocytes.

Antibodies, Monoclonal↗
PubMed1996

Platelet-activating factor and leukotrienes in acute otitis media, secretory otitis media, and chronic otitis media on the acute excerbation.

The present study was carried out for the purpose of measuring platelet activating factor (PAF) and leukotrienes (LTs) in middle ear fluid (MEF) or in otorrhea of children with acute otitis media (AOM), with secretory otitis media (SOM), and with chronic otitis media (COM) on the acute exacerbation. PAF, LTC4, and LTD4+LTE4 concentrations were measured by radioimmunoassay in purulent MEFs obtained from 15 ears of 15 children with AOM, in mucoid or gluey MEFs from 16 ears of 15 children with SOM, and in purulent otorrhea from 9 ears of 9 children with COM on the acute exacerbation. PAF concentrations were 25.4 +/- 9.0 ng/mg total phospholipid (TPL) in AOM, 4.9 +/- 1.9 ng/mg TPL in SOM, 20.7 +/- 15.7 ng/mg TPL in COM, demonstrating significant differences between AOM and SOM (p < 0.05) and between COM and SOM (p < 0.01). LTC4 concentrations were 92.9 +/- 73.8 pg/mg total protein (TP) in AOM, 52.0 +/- 42.5 pg/mg TP in SOM, and 28.5 +/- 11.2 pg/mg TP in COM. LTD4+LTE4 concentrations were 326.5 +/- 177.0 pg/mg TP in AOM, 288.2 +/- 144.6 pg/mg TP in SOM, and 94.0 +/- 58.1 pg/mg TP in COM, demonstrating significant differences between AOM and COM and between SOM and COM (p < 0.01). The results obtained indicated that PAF was involved in the onset of AOM and COM on the acute exacerbation, and that LTs played an important role in SOM.

Acute Disease↗
PubMed1996

Monitoring of procainamide and N-acetylprocainamide concentration in saliva after oral administration of procainamide.

The aim of this study was to evaluate saliva as a potential monitoring medium for procainamide (PA) and its metabolite, N-acetylprocainamide (NAPA). Saliva concentrations of PA and NAPA were determined both in single and repeated oral administration of PA in four healthy subjects. PA and NAPA were detected both in serum and saliva after 500 mg of single oral administration of PA. After single oral administration, serum and saliva concentrations of PA and NAPA reached peak levels at about 1 h and declined thereafter. The mean half-lives of PA were 2.35 h in serum and 1.28 h in saliva. The mean half-lives of NAPA were 5.29 h in serum and 5.01 h in saliva. In this study, PA and NAPA concentrations in saliva were nearly twice as high as those in serum upon chronic oral administration as well as those in a single oral dose of PA. Significant correlation coefficients were observed between serum and saliva concentrations of PA (r = 0.78, p < 0.001, n = 21) and NAPA (r = 0.76, p > 0.001, n = 21) in single oral administration of PA. Significant correlation coefficients were also observed between serum and saliva concentrations of PA (r = 0.89, p < 0.001, n = 17) and NAPA (r = 0.87, p > 0.001, n = 19) after repeated oral administration of PA. The saliva-to-serum ratios of PA and NAPA maintained nearly constant at 1 h after oral administration. It would appear from this study that saliva is a suitable medium for monitoring PA and NAPA concentration regarding acetylator status.

Journal Article↗
PubMed1996

Serum albumin for estimating creatinine clearance in the elderly with muscle atrophy.

The present study was conducted to develop a special formula to predict creatinine clearance (CCr, ml/min) in the elderly with chronic muscle atrophy using serum albumin (Alb, g/dl). We obtained 90 data sets including actual body weight (BW, kg), urinary creatinine excretion (UCr, mg/24 h), serum creatinine (SCr, mg/dl), and Alb from 90 inpatients aged 60-92 years. Regression equations were determined between the dependent variable of UCr/BW and the explanatory variable of Alb as follows: For males Ucr/BW = 2.695 Alb + 4.665 For females Ucr/BW = 1.827 Alb + 4.146. Then, the new predictive formula was derived from the equations: For males CCr = (19Alb + 32)BW/(100 x SCr) For females CCr = (13Alb + 29)BW/(100 x SCr). Evaluations for the predictive error (predicted CCr- measured CCr) showed that the new formula could provide more accurate and less biased estimates of CCr than the Cockcroft and Gault formula could, even in patients with renal insufficiency and in those with Alb < or = 2.8 g/dl.

Aged↗
PubMed1996

[A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in rats].

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 4 weeks was studied in Slc:SD rats at doses of 4, 20 and 100 micrograms/kg/day as low, mid and high dose levels. 1. One male and female at high dose died probably due to stress and circulatory failure. One female at mid dose died with clonic convulsion considered to be results in attached error of a neck collar. Survival of rats showed reddish tear, reddening and desquamation of the skin at application site, and vocalization at all groups including control. Furthermore, abnormal gait, dirty hair, emaciation and opacity of the eyeball surface in both sexes were observed at high dose. 2. A decreased body weight and a slight increased water consumption in both sexes, and a decreased food consumption in males were observed at high dose. 3. An increased incidence of corneal opacity was noted significantly in both sexes as compared with control at high dose. Urinalysis revealed an increased Ca excretion in both sexes at more than mid dose, and lower pH in females at mid dose and in both sexes at high dose, and a decreased urinary volume in males at high dose. The increases of neutrophil and serum beta-globulin ratios in females, and serum Ca level in both sexes were observed at high dose. The increased mineralization of the cornea in males at mid dose and in both sexes at high dose, and of the Kidney in males at high dose were observed. At the skin of application site, cellular infiltration in the epidermis and dermis in both sexes at more than mid dose was observed. Furthermore, hyperplasia of the squamous cell in females, and hyperkeratosis in the epidermis and hypertrophy of the sebaceous gland in both sexes were observed at high dose. 4. After a 4-week recovery period, the changes related with application disappeared except for opacity of the eyeball surface and cornea, and mineralization of organs. 5. On the basis of results obtained in the present study, it is considered that 4 micrograms/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

Administration, Cutaneous↗
PubMed1996

A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in dogs.

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a 4-week recovery was studied in beagle dogs at doses of 0.04, 0.4 and 4 micrograms/kg/day. 1. In general conditions, reddening, desquamation, rash, and wet and hot skin were observed at the skin of application site at 4 micrograms/kg/day. 2. In urinalysis, a tendency to an increase in Ca level, was observed at 4 micrograms/kg/ day. In hematology, an increase in the segmented neutrophils and tendency to a decrease in the lymphocyte counts were observed at 4 micrograms/kg/day. In biochemistry of serum, an increase in gamma-globulin ratio, and decreases in A/G and albumin ratios were observed at 4 micrograms/kg/day. 3. In organ weights, tendency to decreases of the absolute and relative weights in the thymus was observed at 4 micrograms/kg/day. 4. Histopathological examination revealed squamous cell hyperplasia and hyperkeratosis at the skin of application site at 4 micrograms/kg/day. 5. The above changes disappeared after the 4-week recovery period and suggested that they were reversible. 6. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.

Administration, Cutaneous↗
PubMed1996

[A 26-week repeated subcutaneous dose toxicity study of calcipotriol (MC903) followed by a 5-week recovery test in rats].

A 26-week repeated subcutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 5 weeks was studied in Slc:SD rats at doses of 0.4, 2 and 10 micrograms/kg/day as low, mid and high dose levels. 1. No mortality during the experimental period was observed in both sexes of all groups including control. An increased incidence of opacity of the eyeball surface in males was noted at high dose. There were no difference in body weight and food consumption between control. An increased water consumption in both sexes was observed at high dose. 2. An increased incidence of the corneal opacity was noted significantly at high dose in both sexes compared with that observed in control. Urinalysis revealed the increased excretions of Ca at more than mid dose, and Na, Cl and IP in males at high dose, and an decreased urinary volume in females and lower pH in both sexes at high dose. An increased serum Ca level in males at mid dose and in both sexes at high dose, and an elevated ALP activity in males at high dose were observed. The increased weights of the kidney in males at more than mid dose and adrenal gland in both sexes at high dose were observed. The increased incidence of mineralization of the cornea and kidney was noted significantly in males at more than mid dose as compared with control. Dilatation of endoplasmic reticulum of distal tubular cells of the kidney in both sexes was observed at high dose on electron microscopic examination. 3. After a 5-week recovery period, the changes related with the treatment of MC903 almost disappeared except for mineralizations of the cornea and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 administered subcutaneously in both sexes of rats.

Adrenal Glands↗
PubMed1996

[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in rats].

A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in Slc:SD rats at doses of 0.8, 4 and 20 micrograms/kg/day as low, mid and high dose levels. 1. No mortality were observed in both sexes of all groups including control. An increased water consumption was observed in females at mid dose and in both sexes at high dose. 2. An increased incidence of the corneal opacity in males at mid dose and in both sexes at high dose was noted significantly as compared with that observed in control. Urinalysis revealed a slight increased urinary volume, increased excretions of Ca and IP, and lower pH in both sexes at more than mid dose. Levels of the serum IP in females and Ca in both sexes were elevated at high dose. 3. The increased weights of the kidney in males and adrenal gland in females were observed at high dose. The kidney in females at mid dose and in both sexes at high dose showed a higher incidence of mineralization than in control. Furthermore, osteosclerosis of the sternum and femur in both sexes, and hyperkeratosis of the skin at application site in females at high dose were observed. Electron microscopic examination revealed no abnormality in the liver and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.8 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

Administration, Cutaneous↗
PubMed1996

[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in dogs].

A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in beagle dogs at doses of 0.04, 0.4 and 4 micrograms/kg/day. 1. In general conditions, reddening, rash, desquamation, pruritus, wet and hot skin at 4 micrograms/kg/day, reddening, rash and desquamation at 0.4 microgram/kg/day, pruritus and desquamation at 0.04 microgram/kg/day, were observed at the skin of application site. 2. In urinalysis, an increase or a tendency to an increase in Ca level, were observed at 4 micrograms/kg/day. 3. Histopathological examinations revealed squamous cell hyperplasia and parakeratosis at the skin of application site in both sexes at 4 micrograms/kg/day. However, these findings were not shown at the skin of application site at 0.4 and 0.04 microgram/kg/day. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.

Administration, Cutaneous↗
PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (1)--A fertility study in rats by subcutaneous administration].

Calcipotriol (MC903), an anti-psoriasic agent, was given subcutaneously at dose levels of 1, 5 and 25 micrograms/kg/day during the pre-pairing period (9 weeks prior to pairing in males and 2 weeks prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (day 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. 1. In the male 25 micrograms/kg group, opacity of the eyeball surface was observed, and depression of body weight gain, and decreases of body weight and food consumption, and increases in the weight of the kidney were statistically significant in comparison with vehicle controls. 2. In the female 25 micrograms/kg group, depression of body weight gain and food consumption were statistically significant in comparison with vehicle controls. 3. No changes in parameters of reproductive performance were seen in any dosed groups. 4. No changes in parameters of implantation performance were seen. There were no treated-related abnormalities in fetal mortality, weights of fetuses, and external, visceral and skeletal examinations. Based on there results, it is considered that in the present study the no-toxic dose levels of MC903 were 5 micrograms/kg/day for parents, 25 micrograms/kg/day for reproductive performance and fetal development.

Animals↗