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K Kunii

Publications and source records attributed to K Kunii.

At least 19 recordsLinked to original sources

Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways.

Orexin-A and -B are neuropeptides that are implicated in the regulation of vigilance states and energy homeostasis. Orexins are specifically produced by neurons located within the lateral hypothalamic area (LHA), a region implicated in the regulation of feeding behavior. Here, we examined the functional interactions between orexins and anorectic factors [leptin, alpha-melanocyte-stimulating hormone (alpha-MSH) and glucagon-like peptide-1 (GLP-1)] in rats. Intracerebroventricular injection of orexin-A (10 nmol) potently augmented food intake in rats. Neuropeptide Y (NPY) (0.3 nmol) and galanin (3 nmol) also induced a transient increase in food intake. Both NPY- and galanin-induced feeding behaviors were completely inhibited by preadministration of leptin (3 microg), while the same or a higher dose (10 microg) of leptin only partially inhibited orexin-A or -B-induced increase of food intake. Preadministration of anorectic peptides (alpha-MSH and GLP-1), which are shown to be regulated by leptin, abolished NPY-induced feeding; however, orexin-induced feeding was only partially inhibited by these anorectic peptides. These observations suggest that NPY- and galanin-induced increases of feeding involve a leptin-sensitive pathway, while orexin-induced feeding involves both leptin-sensitive and -insensitive pathways.

Animals↗

A new extraction method for Acinetobacter species ODB-L2 rough form lipopolysaccharide from culture broth.

The Gram-negative bacterium Acinetobacter species ODB-L2 produces lipopolysaccharide (LPS) in culture broth. The LPS could not be purified by conventional extraction methods using 90% phenol/water or 90% phenol/chloroform/petroleum ether mixed solvent. Extraction was achieved employing an admixture of chloroform, ethanol, and 4 M HCI solution. The LPS was purified from dissolving the crude extracts in 90% phenol and LPS sediment formed by addition of methanol. The LPS was characterized by chemical, biochemical, and physicochemical methods as rough form 3-hydroxydodecanoic acid rich LPS.

Acinetobacter↗

Orexin-induced food intake involves neuropeptide Y pathway.

Orexins (orexin-A and -B) are recently identified neuropeptides, which are thought to be implicated in the regulation of feeding behavior. We used a NPY-Y1 receptor specific antagonist, BIBO3304, to examine whether NPY is involved in orexin-induced feeding behavior. Intracerebroventricular administration of orexin-A (10 nmol) induced food intake in rats (food intake for 3 h; vehicle 0.3+/-0.2 g vs. orexin-A 10 nmol, 4.0+/-0.5 g, n=4). Orexin-induced feeding behavior was partially inhibited by prior administration of BIBO3304 (3 h food intake: orexin-A 10 nmol, 4.0+/-0.5 g vs. BIBO3304 (60 microgram) + orexin-A 10 nmol, 2.2+/-0.2 g, n=4). A low dose of BIBO3304 (30 microgram) did not show a significant inhibitory effect. BIBO3457, an inactive enantiomer, used as a negative control, did not show any inhibitory effect on orexin-A-induced feeding behavior. Fos expression was observed in NPY-containing neurons in the arcuate nucleus 1 h after orexin-A (10 nmol) was administered intracerebroventricularly (control 0.3+/-0.08%, orexin-A 10.2+/-0.8%, n=5 rats/group). These observations suggest that NPY is involved in orexin-induced feeding behavior. However, BIBO3304 did not completely abolish the effect of orexin-A. These results suggest that orexin-A elicits feeding behavior partially via the NPY pathway. The NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior. Another pathway may also be involved in orexin-A-induced feeding behavior, because BIBO3304 did not completely abolish orexin-A-induced feeding behavior.

Animals↗

Orexins/hypocretins regulate drinking behaviour.

Orexin/hypocretins are recently identified neuropeptides which regulate feeding behaviour. We found orexins increased water intake when administrated intracerebroventricularly to rats. The effect of orexin-A was more potent as compared with orexin-B, suggesting the possible involvement of OX(1) receptor. The efficacy of orexin-A was almost comparable with that of angiotensin II, and the effect lasted more than 3 h. Prepro-orexin mRNA level was up-regulated when rats were deprived of water. Orexin-immunoreactive varicose axons were observed in the subfornical organ and area postrema, regions implicated in drinking behaviour. These observations suggest a physiological role for orexin as mediators that regulate drinking behaviour.

Angiotensin II↗

Concentration of levofloxacin in cervical mucus and its clinical effects on cervicitis.

An investigation was made on the concentration of levofloxacin (LVFX) in cervical mucus and its clinical effects on cervicitis. The results were as follows: 1) The concentrations of orally administered LVFX in the cervical mucus of 110 subjects were determined by HPLC. During 1-4 hour after the administration the mean concentration of LVFX in the cervical mucus reached a level of 2 micrograms/g, which was higher than the serum level. The transfer of LVFX to the cervical mucus was almost the same as that to other genital organs. 2) When LVFX was given to 102 patients at a dose of 100-200 mg, t.i.d for 4-5 days and the efficacy was evaluated with clinical improvement, the clinical efficacy rate of LVFX was 72/102 (70.6%). Significant bacteriological effects were observed in 70/73 (95.9%), especially, the disappearance rate of C. trachomatis was 18/18 (100%). 3) The administration LVFX did not cause any subjective or objective side effects and any abnormalities were not detected in the laboratory test done in this study. These results demonstrate that LVFX can be sufficiently transferred to the cervical mucus for the treatment of cervicitis due to the infection of C. trachomatis etc.

Adult↗

[Pharmacokinetic and clinical evaluation of levofloxacin in obstetrics and gynecology].

Levofloxacin (LVFX, DR-3355), a new synthetic quinolone derivative antibacterial agent, was evaluated for its pharmacokinetics and clinical efficacy in obstetric and gynecological infections, and the following results were obtained. Concentrations of LVFX in serum and intrapelvic genital organs such as uterine and adnexal tissues were determined following oral administration of 100 mg. Tissue penetration of LVFX was found to be good, with its tissue levels (Cmax) of 1.17-2.16 micrograms/ml or g after inhalation anaesthesia and 1.15-2.17 micrograms/ml or g after lumbar spinal anaesthesia. LVFX was given to 22 cases of obstetric and gynecological infections with a daily dose of 200-600 mg for 3-14 days and its clinical efficacy was 95% and bacteriological response was 100%. No side effect was observed. From these findings, we consider that LVFX will be a useful antibacterial agent against obstetric and gynecological infections.

Administration, Oral↗

[Studies on flomoxef in the perinatal period].

Pharmacokinetic, bacteriological and clinical studies on flomoxef (FMOX) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of FMOX on the growth of methicillin-resistant Staphylococcus aureus (MRSA, MIC 400 micrograms/ml), methicillin-sensitive S. aureus (MSSA, MIC 0.78 microgram/ml), Escherichia coli (MIC 3.13 micrograms/ml and MIC 0.20 microgram/ml) in amniotic fluid were determined and it was found that the activity of FMOX was enhanced in the amniotic fluid. FMOX rapidly penetrated into tissues and sera of pregnant women upon intravenous injection and its maternal serum concentrations reached their peak levels shortly after administration. Placental penetration of FMOX to the fetus was good and, after single intravenous injection of 1 g, the concentrations of FMOX in the umbilical cord serum and amniotic fluid exceeded MICs against major causative organisms of perinatal infections. These results indicate that single intravenous injection of FMOX 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of FMOX for the treatment of 14 cases of puerperal infections showed excellent clinical effectiveness with 100% clinical effect and 81.8% bacteriological response. No side-effect was observed in any case. All of these results suggested clinical usefulness of FMOX in the perinatal period.

Adult↗

[Studies on aztreonam in the perinatal period].

Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of AZT on bacterial growth of Escherichia coli (MIC 12.5 micrograms/ml) and Pseudomonas aeruginosa (MIC 50 micrograms/ml) in amniotic fluid were determined and it was found that the activity of AZT is enhanced in amniotic fluid. AZT rapidly penetrated into tissues and sera of pregnant women upon intravenous (i.v.) injection and its maternal serum concentrations reached their peak levels shortly after the injection. Placental penetration of AZT to the fetus was good and, after single i.v. injection of 1 g, the concentrations of AZT in the umbilical cord serum and amniotic fluid exceeded MICs against major Gram-negative bacilli. These results indicate that single i.v. injection of AZT 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of AZT for the treatment of puerperal infections showed excellent clinical effectiveness with 100% eradication of aerobic Gram-negative rods. No side-effect was observed in any case. All of the results suggested clinical usefulness of AZT in the perinatal period.

Adult↗

[Pharmacokinetic studies on cefsulodin in perinatal period].

Pharmacokinetic studies on cefsulodin (CFS) were carried out in perinatal mothers and infants. The results obtained are summarized as follows. 1. CFS was promptly absorbed upon intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus occurred quickly and at high levels. Upon intravenous drip infusion of 1-2 g of CFS, drug concentration of the cord blood and amniotic fluid exceeded MICs of clinically isolated strains of Pseudomonas aeruginosa. These levels in cord blood ranged 3.3-16.9 micrograms/ml upon 1 g intravenous drip infusion and 0.8-21.6 micrograms/ml upon 2 g intravenous drip infusion, and in amniotic fluid they were 1.3-15.6 micrograms/ml upon 1 g administration and 5.5-17.9 micrograms/ml upon 2 g administration. The drug was transferred into newborn infant through placenta, showing no tendency to accumulate. According to the above results, it appears possible to successfully prevent or treat perinatal infections through administration of the dose of 1-2 g twice daily. 2. Moreover, newborn infants delivered from mothers receiving CFS administration showed no laboratory test abnormalities. 3. The penetration of CFS into mother's milk occurred at low levels, and the transference from milk to newborn infants appeared to occur at even low levels. The above results have demonstrated that CFS is a clinically useful antibiotic for prophylaxis and treatment of perinatal Pseudomonas infections.

Cefsulodin↗

[Pharmacokinetic and clinical studies on cefodizime in obstetrics and gynecology].

Cefodizime (CDZM), a new cephem antibiotic, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results are summarized as follows: Concentrations of CDZM in serum and genital tissues following 1 g drip infusion (30 min.) were determined and good penetration of CDZM into tissues was recognized. The maximum level in uterine arterial serum was 56.25 micrograms/ml and maximum tissue levels ranged 23.56-40.64 micrograms/g which were above its MIC80's for main pathogenic organisms. Peak concentrations of CDZM in pelvic dead space exudates following 1 g intravenous bolus injection or drip infusion ranged 6.25-6.52 micrograms/ml. The clinical efficacy of CDZM in 17 cases of obstetrical and gynecological infections was investigated using a dose of 1-3 g daily. The clinical efficacy rate was 88.2% (15/17 cases). Bacteriologically, the eradication rate was 83.3%. No side effects or abnormal laboratory test values were observed.

Adult↗

[Fundamental and clinical studies on cefmenoxime in perinatal period].

Pharmacokinetic studies and clinical evaluations of cefmenoxime (CMX) were carried out in perinatal mothers and infants. The following results obtained are summarized as follows. 1. CMX was promptly absorbed upon intravenous injection in pregnant women, reached dose-related peak serum level shortly after administration. Placental penetration into the fetus occurred quickly and at high levels. After intravenous injection of 1 g of CMX, drug concentrations in the cord blood and amniotic fluid exceeded MICs of main pathogenic organisms. The drug transferred into newborn infants were followed by measuring serum level of the newborn. These levels were related to levels of umbilical cord blood and the drug was eliminated gradually from the newborn without accumulation. According to the above results, it appears possible to successfully prevent or treat perinatal infections, through administration of the dose of 1 g twice daily. 2. Clinically, CMX was effective in the treatment of perinatal infections and prophylaxis of intra-uterine amniotic infections without any severe side effect. 3. Moreover, newborn infants delivered from mothers receiving CMX treatment were without abnormalities in laboratory test results. 4. The penetration of CMX into mother's milk was hardly observed and the transference from milk to newborn infants appeared to be occur only at very low levels. The above results have demonstrated that CMX is a clinically useful antibiotic for prophylaxis and treatment of perinatal infections.

Bacterial Infections↗

[Studies of ceftizoxime in perinatal period].

Bacteriological studies and clinical evaluations of ceftizoxime (CZX) in perinatal period were carried out, and results are summarised as follows: Antibacterial activities of CZX in amniotic fluid were determined using the broth dilution method, and bactericidal effect on Streptococcus agalactiae, Staphylococcus aureus and Escherichia coli were demonstrated. The bactericidal effect of CZX increased in amniotic fluid and remarkable increases of activities against resistant strains were demonstrated. The penetration of CZX into mother's milk was low, and it was speculated that the drug transfer to the newborn through breast feeding was very little. Clinically, CZX was effective in the treatment of perinatal infections without any side effect. The above results has demonstrated that CZX is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Adult↗

[Studies on imipenem/cilastatin sodium in the perinatal period].

Pharmacokinetic, bacteriological and clinical studies of imipenem/cilastatin sodium (IPM/CS) were carried out in the perinatal period, and the results obtained are summarized as follows: Effects of IPM on bacterial growth curves of Staphylococcus aureus (sensitive and resistant strains) and Escherichia coli (sensitive strains) in amniotic fluid were determined. The bactericidal effects of IPM increased in amniotic fluid and remarkable increases against resistant strains were demonstrated. IPM and CS were detected promptly after intravenous drip infusion to pregnant women, and reached peak levels shortly after administration in maternal plasma. Placental penetration of IPM and CS to the fetus was favorable. After intravenous drip infusion of 500 mg/500 mg of IPM/CS, drug concentrations in the umbilical cord plasma and the amniotic fluid exceeded MICs against main pathogenic organisms. Clinically, IPM/CS was effective in the treatment of perinatal infections without any side effect. The above results demonstrated that IPM/CS is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Adult↗

[Bacteriological, pharmacokinetic and clinical studies on the use of ceftriaxone in the perinatal period].

Laboratory studies and clinical evaluation of ceftriaxone (CTRX) were carried out with mothers and infants in perinatal period. The presence of synergistic effect between CTRX and amniotic fluid were studied using a broth dilution method. Stronger effects were recognized when both agents were present together compared to each agent alone by the fact that values of MIC and MBC became closer together for Escherichia coli as well as for Streptococcus agalactiae. Against the growth of E. coli, a synergism was observed, but for S. agalactiae, only an additive effect was found. The placental transmission of CTRX upon the administration was rapid, and the blood CTRX level reached its peak shortly after the intravenous administration of the drug. The transport of the drug into the fetus through placenta was excellent and one dose of 1 g of CTRX gave drug concentrations in the umbilical cord serum and amniotic fluid higher than MIC's against main pathogenic organisms. According to these results, it should be possible to treat or prevent perinatal infections by a dose of one gram per day of CTRX, once or twice daily. Cases of perinatal infections were treated with CTRX. An effective treatment without side effects was obtained. No physical abnormalities nor unusual laboratory test results were recognized in neonates delivered from mothers who received CTRX administration. The penetration of CTRX into mothers' milk was low, thus the drug transfer into neonates through the breast-feeding should not be a problem. It appears, from the above study, that CTRX is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Adult↗

[Clinical studies of BRL 28500 (clavulanic acid/ticarcillin) in the treatment of pelvioperitonitis and Douglas' abscess].

Clinical studies were conducted on BRL 28500 (a formulation containing 15 parts ticarcillin plus 1 part clavulanic acid). BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i.d., generally for 10 days by drip infusion to patients with pelvioperitonitis or Douglas' abscess. The results obtained were summarized as follows. 1. Clinical efficacy was evaluated in 18 patients (pelvioperitonitis 14, Douglas' abscess 4), but 8 patients out of a total of 26 patients were excluded. 2. In the evaluation of clinical improvement by doctors in charge, clinical improvement rates were 44.4% on day 3, 88.2% on day 5. 3. On the basis of committee judgement, the clinical efficacy rate was 100%. 4. The bacteriological eradication rate of causative organisms was 100% in 11 patients (15 strains). Five strains out of a total of 15 strains produced beta-lactamase. 5. As a side effect, nausea was observed in 1 case. In laboratory examination, liver function abnormalities were observed in 1 case. 6. Regarding usefulness as judged by doctors in charge, the satisfactory rate was 83.3%. From the above results, it has been concluded that BRL 28500 is very useful in the treatment of pelvioperitonitis and Douglas' abscess.

Abscess↗

[Pharmacokinetic and clinical studies on cefuzonam in obstetrics and gynecology].

Cefuzonam (CZON), a new cephem antibiotic agent, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results were summarized as follows. 1. The absorption and the tissue penetration of CZON into intrapelvic genital organs were good. The peak serum level in uterine artery after an intravenous drip infusion of 1.0 g was 49.0 micrograms/ml, and the highest peak level of 23.0 micrograms/g in tissues was obtained. After drip infusion of 2.0 g, the peak serum level in uterine artery was 137 micrograms/ml and the highest peak tissue concentration was 54.6 micrograms/g. Tissue concentrations of the drug changed in a similar pattern to serum levels and a dose-dependent response was recognized. 2. The penetration of CZON into intrapelvic dead space exudate was good. The level reached a peak of 8.17 micrograms/ml 4 hours after and intravenous drip infusion of 1.0 g and diminished slowly. 3. The clinical efficacy of CZON at a daily dose of 2 g was evaluated in 21 cases of obstetrics and gynecologic infections. The efficacy rate was 85.7% (18/21 cases). Bacteriologically, the eradication rate obtained was 93.3%. No side effects or abnormal laboratory values were observed.

Adult↗

[Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

A combination of imipenem (MK-0787), a new carbapenem antibiotic, plus cilastatin sodium (MK-0791), a dehydropeptidase inhibitor (MK-0787/MK-0791 = 1:1) was studied in the field of obstetrics and gynecology and the following results were obtained. Absorption and penetration into genital organ tissues were good. Following a 0.5 g/0.5 g intravenous drip infusion, the maximum plasma concentration in uterine arterial blood was 20.8 micrograms/ml, and the maximum concentrations of the drug in tissues were 9.9 approximately 16.8 micrograms/g, and these levels of MK-0787 exceeded the MIC values against main causative organisms. Rates of elimination of the drug from the tissue and from the plasma were similar. Against gynecological and obstetrical infections, a dose of 0.5 g/0.5 g twice daily for an average duration of 6.3 days produced a clinical efficacy ratio of 94.4% (17/18) and a bacteriological effects rating of 76.9% (10/13). As side effects, one patient showed an eruption and another had an elevated GOT and GPT. Based on the above results, MK-0787/MK-0791 appears to be effective against gynecological and obstetrical infections.

Adult↗