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1.
Hideki Kawaguchi Kazuko Masuo Tomohiro Katsuya Ken Sugimoto Hiromi Rakugi Toshio Ogihara Michael L Tuck 《Hypertension research》2006,29(12):951-959
High blood pressure (BP) is a major determinant of cardiovascular events in obesity. The beta2- and beta3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta2- and beta3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BP, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta2(Arg16Gly)- and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI]> or =25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as > or =10% increases from entry levels over 5 years in mean BP or BMI. Obese subjects with weight gain, BP elevation or weight gain-induced BP elevation had higher frequencies of the Gly16 allele of Arg16GIy and Arg64 allele of Trp64Arg. Subjects carrying the Gly16 or Arg64 alleles had significantly greater total fat-mass and waist-to-hip ratio at entry and over a 5-year period compared to the subjects who did not carry these polymorphisms. Subjects carrying the Gly16 allele had similar levels of plasma NE, higher levels of plasma leptin and a lower slope of the regression lines between plasma leptin and NE levels. Those carrying the Arg64 allele had higher plasma NE levels at entry and over a 5-year period compared to the subjects without the Arg64 allele, but plasma leptin levels and slopes were similar. The findings demonstrate that the Arg64 allele of the beta3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects. 相似文献
2.
Yuko Kamio Yurika Saito Naoki Utoguchi Masuo Kondoh Naoya Koizumi Makiko Fujii Yoshiteru Watanabe 《Journal of controlled release》2005,102(3):563-568
Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs. 相似文献
3.
Sumie Yamanaka Masanori Hashimoto Masuo Tobe Kazuo Kobayashi Jun Sekizawa Masao Nishimura 《Archives of toxicology》1990,64(4):262-268
We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2–2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.This work was supported by a grant from Ministry of Health and Welfare in Japan (No. 467 and 511) 相似文献
4.
Goichi Yotsumoto Koki Tanaka Naoki Ishizaki Akira Ikoma Sumihiro Kawashima Akira Taira 《Surgery today》1997,27(7):657-660
We report herein a case of spontaneous subcapsular hepatic hemorrhage which occurred in a 33-year-old woman 1 day after she
had been delivered of her second child by cesarean section following an uneventful pregnancy. She complained of right upper
quadrant pain on the 1st postoperative day, and computed tomography (CT) showed subcapsular low-density masses in both liver
lobes, while extravasation was demonstrated by CO2 intraarterial digital subtraction angiography (IADSA). The hemorrhage was successfully controlled by transcatheter arterial
embolization (TAE). However, on the 3rd day after TAE, an exploratory laparotomy was performed to establish an exact diagnosis
to explain the persistent abdominal pain and abnormal liver function tests. Subcapsular hematomas in both lobes were confirmed
and no visible laceration was present. The patient recovered gradually by spontaneous absorption of the hematomas and was
discharged on the 22nd postoperative day. Spontaneous hepatic hemorrhage associated with pregnancy is a very rare complication,
and establishing a correct diagnosis and initiating appropriate therapy are essential for this life-threatening disease. 相似文献
5.
Fumiki Oana Toshiki Homma Hiroo Takeda Akane Matsuzawa Satoshi Akahane Masayuki Isaji Masuo Akahane 《Pharmacological research》2005,52(5):395-400
We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism. 相似文献
6.
Shuichiro Uchiyama Kazuo Chijiiwa Masahide Hiyoshi Motoaki Nagano Jiro Ohuchida Koki Nagaike Masahiro Kai Kazuhiro Kondo 《Journal of gastrointestinal surgery》2007,11(11):1570-1572
Mucin-producing tumor in the bile duct is referred to clinically as mucin-producing bile duct tumor (MPBT). Intraductal papillary
neoplasm of the biliary tract that resembles an intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a rare category
of MPBT and is not well characterized. We, herein, report a case of MPBT of the caudate lobe of the liver that showed papillary
growth and communicated with the bile duct of the caudate lobe and protruded into the common hepatic duct. Histologically,
MPBT cells showed papillary overgrowth with abundant mucinous secretions, resembling an IPMN of the pancreas. The MPBT cells
showed the same immunostaining pattern as that of cells from IPMN of the pancreas. 相似文献
7.
Hikaru Tanaka Naofumi Uesato Koki Shigenobu 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(4):391-397
Chronotropic and inotropic effects of histamine were examined in isolated atrial and ventricular preparations from embryonic and hatched chicken hearts. Histamine produced positive chronotropic and inotropic responses both in embryonic and hatched hearts. The responses to histamine in middle embryonic myocardia, which were observed in the micromolar range, were antagonized by H2 antagonists but not by H1, H3 antagonists and propranolol. Isobutylmethylxantine, an inhibitor of phosphodiesterase, produced a leftward shift of the concentration-response curve for the chronotropic effect of histamine in the embryo. The responses to histamine in myocardia from hatched chicks, which were observed in the milimolar range, appeared concurrently with the responses to tyramine during development and were antagonized by beta adrenoceptor antagonists but not by any of the histamine antagonists. The positive inotropic response to histamine in hatched ventricular preparations were greatly attenuated by reserpine pretreatment or in the presence of desipramine. Thus, we demonstrated that exogenously applied histamine produces positive chronotropic and inotropic responses in developing chicken hearts and that the mechanisms are different between embryonic and hatched chicks: direct action on H2 receptors in the embryonic heart and release of norepinephrine from sympathetic nerve terminals in hatched hearts. 相似文献
8.
Opioid supplements are often required in total intravenous anesthesia (TIVA). Most ϰ-opiate receptors are found in the spinal
cord, wherea μ-opiate receptors are widespread throughout the brain and spinal cord. Buprenorphine has a strong μ-action with
a minute ϰ-action, while eptazocine stimulates ϰ-receptors only. From these, epidural eptazocine is expected to exert strong
spinal analgesia by ϰ-stimulation without μ-action, which produces circulatory and respiratory depression. Therefore, the
clinical effects of epidural opioids on circulation, respiration, and analgesia were compared. Continuous epidural administration
of eptazocine or buprenorphine was combined with TIVA in patients scheduled for elective abdominal surgery. Epidural opioid
administration was continued throughout and for 72h after anesthesia. A significant analgesic effect (P<0.01) of epidural eptazocine without circulatory and respiratory depression was observed. With epidural buprenorphine, circulatory
and respiratory depression during and immediately after anesthesia were significant (P<0.05). These results suggest that medullary μ-stimulation by an epidural opioid induces circulatory (hypervagotonicity and
hypervagosensitivity) and respiratory depression, while ϰ-stimulation produces only minimal effects on circulatory and respiratory
systems. 相似文献
9.
H King C Finch A Collins G Koki L F King P Heywood P Zimmet 《The Medical journal of Australia》1989,151(4):204-210
That Melanesians of non-Austronesian genetic ancestry may be relatively resistant to glucose intolerance was supported by the results of a study of two semitraditional non-Austronesian villages in the Papua New Guinean highlands in 1983, in which an absence of diabetes and a high degree of glucose tolerance and insulin sensitivity were observed. The second of this series of surveys was conducted in 1985 in three non-traditional communities: a periurban, non-Austronesian village in the highlands, and rural and periurban Austronesian villages in coastal locations. Although an absence of diabetes was demonstrated once again in the highlanders, these periurban subjects showed an unexpectedly high insulin response which may be a precursor of glucose intolerance. The notion that highland communities that are living in non-traditional circumstances in Papua New Guinea presently are in "metabolic transition" towards diabetes and other non-communicable diseases, if correct, is of importance to the public health of the nation. In the periurban, coastal-dwelling Austronesians, diabetes with severe hyperglycaemia was demonstrated, and there was some evidence of a secular trend towards increasing glucose intolerance. The two-hour plasma glucose concentrations were shown to be associated with obesity, modernity and Seventh-Day Adventist religious persuasion. However, important and unexplained differences in glucose tolerance remained between rural and periurban coastal dwellers after taking these factors into account. 相似文献
10.
Koichiro Yuji Shigesaburo Miyakoshi Daisuke Kato Yuji Miura Tomohiro Myojo Naoko Murashige Yukiko Kishi Kazuhiro Kobayashi Eiji Kusumi Hiroto Narimatsu Tamae Hamaki Tomoko Matsumura Masahiro Kami Takahiro Fukuda Shigeru Masuo Kazuhiro Masuoka Atsushi Wake Junichi Ueyama Akiko Yoneyama Ko Miyamoto Haruhisa Nagoshi Michio Matsuzaki Shinichi Morinaga Yoshitomo Muto Yoichi Takeue Shuichi Taniguchi 《Biology of blood and marrow transplantation》2005,11(4):314-318
We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor. 相似文献