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排序方式: 共有313条查询结果,搜索用时 109 毫秒
1.
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
2.
Alterations in thyrotropin-releasing hormone (TRH) content in the brain during hemorrhagic shock were examined in conscious rats, and the results were interpreted in relation to the reversibility of the shock. Two sets of experiments were run. The first one was to establish reversible and irreversible shock models. Hemorrhagic shock was induced by the initial withdrawal of 4 ml of blood followed by 1 ml bleeds at 5, 15, 30, and 60 min to maintain the blood pressure at 40-70 mmHg for 60 min. Blood withdrawn during and 60 min after the end of the shock was used to measure plasma lactate levels and blood gases. Shock was considered to be reversible if the animal survived for 24 hr after the hemorrhage. The plasma lactate levels as well as Base Excess and PaCO2 during and 60 min after the end of the hemorrhage of the surviving rats were significantly different from those of the animals which died within 24 hr. In particular, the plasma lactate levels at 60 min after the end of the hemorrhagic period were good indicators of the mortality of animals; it was predicted that rats whose plasma lactate levels are higher than 3.8 mEq/L would die within 24 hr (0.69% probability of misdiscrimination). The second experiment was to measure brain TRH content during and after hemorrhage produced using the same bleeding procedure as the first. During hemorrhage, brain TRH contents in the medulla oblongata and midbrain were found to be significantly increased compared with the control values. At 60 min after the end of hemorrhage, significantly higher TRH content values were obtained in the medulla oblongata, midbrain, cerebral cortex, striatum, and cerebellum in the rats whose plasma lactate levels were lower than 3.8 mEq/L compared with those of animals having plasma lactate values higher than 3.8 mEq/L. From the results of the two sets of experiments, it is concluded that the surviving animals have more TRH in the brain regions mentioned above than the non-surviving animals after hemorrhagic shock, and it is suggested that brain TRH plays a beneficial role in the course of recovery from hemorrhagic shock. 相似文献
3.
Ichiyasu H Suga M Matsukawa A Iyonaga K Mizobe T Takahashi T Ando M 《Journal of leukocyte biology》1999,65(4):482-491
The immunological manifestation of granuloma formations in humans largely depends on the delayed-type hypersensitivity response. We investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in a rabbit model of T cell-mediated pulmonary granulomatosis. Intravenous injection of Propionibacterium acnes (P. acnes) into sensitized rabbits induced massive and diffuse pulmonary granulomas. Levels of MCP-1 in sera and bronchoalveolar lavage fluids (BALF) peaked before the granuloma formation reached the peak (on days 1 and 3 after challenge, respectively). Chemotactic activities toward monocytes and T cells in BALF were inhibited by anti-MCP-1 IgG by 80 and 36%, respectively. The phenotypic analysis of the migrating T cells revealed that activated and memory T cells rather than naive cells were preferentially attracted to the BALF. Administration of anti-MCP-1 antiserum inhibited the development of granuloma formation in both size and number, the numbers of infiltrating leukocytes in BALF, the expression of adhesion molecules on peripheral monocytes/T cells, and on macrophages/T cells in BALF, and the production of TNF-alpha in the lung. Anti-MCP-1 resulted in a trend toward decreased level of IL-1beta in the lung. The inhibition of the production of these cytokines appeared to be induced indirectly through the inhibition of the recruitment of macrophages that produce these cytokines. The results suggest important roles of MCP-1 in the development of granuloma formation in this model through the attraction and activation of specific types of cells. 相似文献
4.
Takeshi Tana Nobuhiro Kamikawaji Christopher J. Savoie Tohru Sudo Yurika Kinoshita T. Sasazuki 《Journal of human genetics》1998,43(1):14-21
Susceptibility to a series of autoimmune diseases is strongly associated with particular HLA class II alleles. Identification
of T cell clones and antigenic epitopes bound by HLA class II molecules involved in autoimmune diseases is critical to understanding
the etiology of these HLA class II-associated diseases. However, establishment of T cell clones in autoimmune diseases is
difficult because the antigenic peptides are unknown. Peptide library methods which include all possible peptide sequences
offer a potentially powerful tool for the detection of cross-reactive antigenic peptides recognized by T cells. Here, we reduced
the number of peptides per mixture by utilizing the known binding motifs of peptides for the HLA-DRB1*0405 molecule and evaluated
the effectiveness of this library design. Each library mixture evoked a strong proliferative response in the unprimed peripheral
blood lymphocytes (PBL) from HLA-DRB1*0405-positive donors but little or no response in the PBL from HLA-DRB1*0405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted
by HLA-DRB1*0405, with different specificities. The motif-based approach thus presents a powerful method for monitoring T
cells in large, heterogeneous T cell populations and is useful for the identification of the mimic peptide epitopes of T cell
lines and clones.
Received: October 3, 1997 / Accepted: October 23, 1997 相似文献
5.
Nozuchi S Mizobe T Aoki H Hiramatsu N Kageyama K Amaya F Uemura K Fujimiya T 《Anesthesiology》2000,92(1):164-170
BACKGROUND: Sevoflurane reportedly inhibits adenosine diphosphate-induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation. METHODS: Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay. RESULTS: Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and 60 +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 +/- 48 nM vs. 142 +/- 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect. CONCLUSIONS: Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin. 相似文献
6.
7.
Yosuke Homma Takashi Shiga Yuiko Hoshina Kenji Numata Michiko Mizobe Yoshiyuki Nakashima Jin Takahashi Tetsuya Inoue Osamu Takahashi Hiraku Funakoshi 《The American journal of emergency medicine》2018,36(4):673-676
Objectives
Acute alcohol intoxication is often treated in emergency departments by intravenous crystalloid fluid (IVF), but it is not clear that this shortens the time to achieving sobriety. The study aim was to investigate the association of IVF infusion and length of stay in the ED.Methods
This single-center retrospective cohort study was conducted in Japan and included patients aged ≥ 20 years of age and treated for acute alcohol intoxication without or with IVF. The primary outcome was the length of the ED stay and the treatments were compared by time-to-event analysis.Results
A total of 106 patients, 42 treated without IVF and 64 with IVF. The baseline characteristics of the two groups were similar. Kaplan–Meier analysis and the generalized Wilcoxon test found no significant difference between the two treatments in the time to ED discharge. The median time was 189 (IQR 160–230) minutes without IVF and 254.5 (203–267 minutes with IVF; p = 0.052). A Cox proportional hazards regression model adjusted for potential confounding variables found that patients treated with IVF were less likely to be discharged earlier than those treated without IVF (HR 0.54, 95% CI: 0.35–0.84, p = 0.006).Conclusions
IVF for treatment of acute alcoholic intoxication prolonged ED length of stay even after adjustment for potential confounders. Patients given IVF for acute alcohol intoxication should be selected with care. 相似文献8.
Sleep-related disordered breathing (SDB) and its influence on desaturation were examined in stable COPD patients with waking SpO2 > 90%. With respiratory inductance plethysmography, thoracic-abdominal respiratory movements for all events with more than 4% desaturation were analyzed in 26 patients. Types of SDB were confirmed by full polysomnography. Irregular breathing induced desaturation, while stable respiration continued during some desaturation events. Three types of altered ventilation were observed: hypoventilation, paradoxical movement and periodic breathing. An unusual type of paradoxical movement, with normal airflow despite progressive desaturation, was observed in REM sleep. Patients were divided into desaturation (15 patients) and non-desaturation (11 patients) groups. Daytime arterial blood gas, lung function values, and 6-min walking distance did not differ. Awake, mode, maximum and minimum nocturnal SpO2 were lower in the desaturation group. SDB-induced desaturation events in the desaturation group were more frequent (9.2+/-3.5 vs. 1.8+/-2.2 times), a greater SpO2 decrease (11.4+/-7.1% vs. 5.2+/-2.1%) and longer duration (73.2+/-34.8 vs. 18.8+/-39.0 min). Patterns of SDB in the desaturation group were hypoventilation (74.4+/-23.4%), paradoxical movement (10.2+/-14.5%), periodic breathing (12.1+/-18.3%) and unclassified (5.8+/-11.2%). These results reveal that lower SpO2 and SDB influence nocturnal desaturation in stable COPD patients. 相似文献
9.
Kenichi Mizobe Yoshihiro Kawabe Yasuhiko Bando Koji Sakiyama Hisao Araki Osamu Amano 《ACTA HISTOCHEMICA ET CYTOCHEMICA》2014,47(6):255-264
Salivary glands repair and regenerate following various types of injuries and surgical procedures. However, the tissue responses induced in the contralateral glands have yet to be elucidated in detail. Hsp27, a member of the heat-shock protein (Hsp) family, is strongly expressed in physiological environments, particularly during development. Hsp27 was previously shown to play a role in the regulation of acinar cell proliferation and differentiation in the rat submandibular gland.The present study performed the following surgical treatments on the right submandibular glands of adult rats: 1) duct ligation followed by unligation after one week; 2) partial sialoadenectomy; and 3) total sialoadenectomy. Immunohistochemistry for Hsp27 and Ki67 was performed in the experimental and normal contralateral glands, and localization was histologically and morphometrically analyzed.The results obtained revealed the localization of Hsp27 to the intercalated duct in the submandibular glands of non-treated rats. The expression of Hsp27 was strongly induced in both the uninjured contralateral control glands as well as treated glands of experimental rats regardless of the surgical procedure performed. The number of Hsp27-immunopositive cells increased rapidly following surgery, and subsequently returned to the same level as that in non-treated rats after 4 weeks. However, no marked changes were observed in the number of Ki67-immunopositive proliferating cells. Therefore, the change in the number of Hsp27-immunopositive cells may have contributed to compensatory hypertrophy. The results of the present study indicate that the expression of Hsp27 in the intercalated duct in the submandibular gland may play a role in the differentiation of acinar cells. 相似文献
10.
Michio Mizobe Seiji Hokimoto Tomonori Akasaka Yuichiro Arima Koichi Kaikita Kazunori Morita Hiroko Miyazaki Kentaro Oniki Kazuko Nakagawa Hisao Ogawa 《Thrombosis research》2014