Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
30 巻 , 2 号
April
選択された号の論文の10件中1~10を表示しています
Full Papers
  • Akihiko Yonezawa, Masaru Yoshizumi, Shin-nosuke Ise, Chizuko Watanabe, ...
    2009 年 30 巻 2 号 p. 71-78
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    It has been suggested that dopamine (DA) and serotonin (5-HT) and their receptors, particularly D2-like and 5-HT2C receptors, may play a significant role in the control of male sexual function. The purpose of this study was to investigate whether the combination of a dopamine receptor agonist apomorphine and a 5-HT2 receptor agonist m-CPP would potentiate penile erection and ejaculation in male rats. Systemic administration of either apomorphine (0.01-0.1 mg/kg, s.c.) or m-CPP (0.01-0.3 mg/kg, i.p.) dose-dependently elicited penile erections, but did not induce ejaculation. When combined, there was a drastic increase in both the incidence of ejaculation and the amount of ejaculated seminal materials, while the proerectile effect induced by each drug was not potentiated. The proejaculatory effect induced by the combination of apomorphine (0.1 mg/kg, s.c.) and m-CPP (0.3 mg/kg, i.p.) was completely blocked by pretreatment with the D2-like receptor antagonists haloperidol and sulpiride, but not by the D1-like receptor antagonist SCH-23390. The synergistic action for ejaculation was also blocked by domperidone, the D2-like receptor antagonist that dose not cross the blood-brain barrier. The rats pretreated with the 5-HT2C receptor antagonist SB242084 did not show the synergistic action by the combination of apomorphine and m-CPP, whereas the rats pretreated with the 5-HT2A receptor antagonist ketanserin and the 5-HT2B receptor antagonist SB204741 showed the combination-induced synergistic action. These results suggest that the combination of a small dose of apomorphine and m-CPP potently and selectively facilitates the ejaculatory response through the activation of D2-like and 5-HT2C receptors, respectively. The D2-like receptors involved in the synergistic action may be, at least in part, located in the peripheral sites.
  • Motonari Ohashi, Tomomi Kusumi, Fuyuki Sato, Yasuyuki Kudo, Hiroyuki J ...
    2009 年 30 巻 2 号 p. 79-86
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    Extrahepatic bile duct carcinoma is one of the most extremely aggressive cancers with poor prognosis after curative resection. Syndecan-1 and E-cadherin are transmembrane glycoproteins, and have important roles in cell-cell adhesion and tumor progression. In this study, we examined 84 surgically resected cases of extrahepatic bile duct adenocarcinoma to clarify clinicopathological significance of syndecan-1/E-cadherin expression. Reduced expressions of syndecan-1 and Ecadherin were found in 69.0% (58/84) and 46.4% (39/84) of the bile duct carcinomas. Reduced syndecan-1 expression was correlated with lymphatic/venous/nervous invasion (P < 0.0001), and was associated with short overall survival (P = 0.0002). Reduced E-cadherin expression was correlated with lymphatic and nervous invasion (P = 0.008, P < 0.0001, respectively), and was associated with short overall survival (P = 0.0038). The results indicated that reduced syndecan-1/E-cadherin expression may be good indicators of recurrence and prognosis in extrahepatic bile duct carcinoma.
  • Hiromi Nishinaga, Rie Komatsu, Masao Doi, Jean-Michel Fustin, Hiroyuki ...
    2009 年 30 巻 2 号 p. 87-93
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    Renal tubular NHE3, the Na+/H+ exchanger, is a critical enzyme for electrolyte and acid-base homeostasis in the kidney. We previously demonstrated that the expression of this gene in the kidney followed a circadian rhythm directly regulated by clock genes acting on E-box elements present on its promoter region. In the present study, we further characterize the circadian expression of NHE3 in the mice kidney by in situ hybridization, and refine quantification of gene expression using real-time PCR combined with laser capture micro-dissection. We show NHE3 mRNA was strongly expressed in the inner stripe of the outer medulla and weakly in the cortex. Further realtime PCR data from dissected medullary nephron demonstrated clear circadian oscillations in the thick ascending limbs and the thin descending limbs, but not in the collecting ducts. The circadian changes of this molecule in the renal medulla may partially contribute to the circadian change of urinary electrolyte secretion.
  • Takahiko Ohishi, Chiyoko Nukuzuma, Akira Seki, Mayumi Watanabe, Chikak ...
    2009 年 30 巻 2 号 p. 95-100
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    The effect of mild hyperthermia on venous blood pH was examined in 6 cancer patients. Mild hyperthermia was induced by continuation of a rectal temperature of 39.5°C for 30 min. All 6 patients were diagnosed as suffering from advanced cancer with or without surgery and chemotherapy pretreatments. In Cases 1 to 5, but not Case 6, venous blood pH was alkalized up to pH 7.7 by this mild hyperthermia and the effect was reproduced depending on the application of hyperthermia. At this time, alkalized pH was accompanied by increased PO2 and decreased PCO2 in the blood. These patients showed good physical conditions and improved clinical data. On the other hand, hyperthermia could not be continued in Case 6 due to his worsened physical condition. The present data suggest that mild hyperthermia is a useful method to improve circulation failure, physical condition and clinical data.
  • Hiromasa Kameya, Nobuo Hokama, Norio Hobara, Susumu Ohshiro, Tsukasa U ...
    2009 年 30 巻 2 号 p. 101-106
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    The aim of this study is to determine whether pramipexole hydrochloride hydrate (PHH) and atropine sulfate affect valproic acid (VPA) pharmacokinetics and to evaluate how plasma VPA concentrations are altered by different PHH administration routes. The following studies were conducted on rats: 1) changes in plasma VPA concentration after simultaneous oral administration (PO) of PHH and VPA-Na; 2) effects of intraperitoneal administration (IP) of PHH on plasma VPA concentration after VPA-Na PO; 3) effects of PHH PO on plasma VPA concentration after intravenous administration (IV) of VPA-Na; and 4) changes in plasma VPA concentration after simultaneous PO of atropine sulfate and VPA-Na. Atropine sulfate PO significantly decreased the area under the concentration-time curve up to 3 h (AUC0-3, the total amount of drug plasma concentration) of VPA, suggesting that atropine sulfate decreases VPA-Na absorption probably due to reduced gastrointestinal motility by its anticholinergic action. Similarly, by PHH PO or IP, VPA AUC0-3 was significantly decreased. However, in cases of VPA-Na IV, all VPA parameters were unchanged by PHH PO. These results indicate that the PHH inhibitory effect may be caused in the absorption phase of VPA by pharmacological action of PHH, and thus PHH decreases VPA-Na bioavailability.
  • Saori Nishijima, Kimio Sugaya, Katsumi Kadekawa, Hidekatsu Naka, Minor ...
    2009 年 30 巻 2 号 p. 107-112
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    We compared the effect of 4 anti-muscarinic agents on bladder activity, urinary ATP levels, and autonomic nervous system in rats. Rats were divided into the following 5 groups (control group, oxybutynin group, propiverine group, tolterodine group, imidafenacin group), and were administered daily the designated anti-muscarinic agent or distilled water into the stomach. After 2 weeks, we performed 1) continuous cystometry with physiological saline and 0.1% acetic acid solution, 2) measurement of urinary ATP level before and after bladder stimulation, and 3) measurement of the heart rate, blood pressure and plasma catecholamines. The maximum bladder contraction pressure increased and the interval between contractions became shorter during cystometry with acetic acid solution in the control group, but not in the 4 anti-muscarinic agent groups. The urinary ATP level increased after bladder stimulation in all groups, but the increase was smaller in the propiverine and imidafenacin groups. The plasma noradrenaline and dopamine levels of the propiverine group were higher. Taken together, all anti-muscarinic agents inhibited the bladder activity without changing the heart rate and blood pressure. Especially, the inhibitory effect of propiverine and imidafenacin on bladder activity may be partly due to blocking an increase of ATP release from the bladder urothelium.
  • Yasumasa Hitomi, Akiko Suzuki, Yoshiro Kawano, Kayoko Nozawa-Inoue, Ma ...
    2009 年 30 巻 2 号 p. 113-119
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    Epithelial sodium channels (ENaCs) are a subfamily of ion channels within the degenerin/ENaC (DEG/ENaC) superfamily. Previous studies have shown the immunolocalization of ENaC in the neural elements of the cutaneous mechanoreceptors as well as dorsal root and trigeminal ganglion neurons, indicating the involvement of this molecule in mechanotransduction. The present study examined the expression of ENaCβ, a major component of ENaC protein, in the mechanoreceptive Ruffini endings in the periodontal ligament of the rat incisors by immunohistochemistry. The expression of ENaCβ in the trigeminal ganglion—which innervates the periodontal Ruffini endings—was also investigated at the mRNA and protein levels. Furthermore, double staining and a nerve injury experiment were applied to clarify its detailed localization in the periodontal Ruffini endings. ENaCβ immunoreaction in the trigeminal ganglion was recognizable in the comparatively large neurons which have been considered to mediate mechanotransduction. Immunohistochemistry for ENaCβ demonstrated dendritic ramifications of the Ruffini endings as well as the rounded cells in the periodontal ligament. Double staining with ENaCβ and either PGP9.5 or S-100 protein showed immunoreaction for ENaCβ in both the axonal and glial elements in the periodontal ligament. Some ENaCβ positive cells with rounded profiles were reactive to non-specific cholinesterase activity. Furthermore, a transection of the inferior alveolar nerve failed to eliminate the rounded cells with ENaCβ reaction, indicating that they were the terminal Schwann cells associated with the periodontal Ruffini endings. These findings suggest that ENaCβ is a key mechanotransducing channel in the periodontal Ruffini endings. Probably, the terminal Schwann cells together with the axon terminals regulate mechanotransduction in the periodontal endings.
  • Hitomi Soumiya, Hidefumi Fukumitsu, Shoei Furukawa
    2009 年 30 巻 2 号 p. 121-128
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    The stem cell factor (SCF)-c-kit signal transduction pathway plays an important role in the proliferation and migration of neural progenitor cells, but little is known about its function during the development of the cerebral cortex. We investigated the effects of SCF by directly administering it into the telencephalic ventricular space of 13.5-day-old mouse embryos. SCF produced the heterotopic accumulation of cortical cells in several distinct area of the cerebral cortex at the postnatal stage, including the subcortical periventricular area, marginal zone, and lateral ventricular space. Additional analysis revealed that the heterotopia included both neurons and astrocytes and that SCF initially increased the number of neural stem cells without affecting that of intermediate progenitors and also disturbed their organization. These results suggest that SCF alters the timing of the genesis and migration of neural stem/progenitor cells, which may lead to formation of the observed heterotopia.
  • Masashi Honda, Yoshizu Nozawa, Taichi Ishizaki, Motonaka Kuroda
    2009 年 30 巻 2 号 p. 129-135
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    Bonito extract (BE) has been shown to improve various fatigue-related symptoms. The possibility that the improvement of blood flow contributes to the improvement of fatigue-related symptoms has been reported. However, even though BE has been found to increase peripheral blood flow in humans, an understanding of its mechanisms has remained elusive. The purpose of the present study is to construct an animal model system with which the blood flow-increasing effects of BE can be examined. Using mice loaded with crowding stress, an attempt was made to reproduce the increases in peripheral blood flow observed in humans after a single administration of BE. In this study, the crowded-condition mice (20 mice/cage) showed significantly increased catecholamine levels (noradrenaline, adrenaline, and dopamine) in their circulating blood and a decreased rate of skin blood perfusion in comparison with the normal-condition mice (6 mice/cage). The rate of skin blood perfusion was significantly increased by BE in the crowded-condition mice in comparison with the controls, but not influenced by BE in the normal-condition mice. This suggests that BE expands the vascular diameter by affecting the constriction of vessels induced by catecholamines.
Communication
  • Masahiro Maki, Hiroaki Miyazaki, Naomi Niisato, Toru Morihara, Yoshino ...
    2009 年 30 巻 2 号 p. 137-140
    発行日: 2009年
    公開日: 2009/05/01
    ジャーナル フリー
    In the preset report, we studied if blockers of the K+/Cl- cotransporter, and Cl- and K+ channels modify the proliferation of MC3T3-E1 osteoblastic cells. A blocker of the K+/Cl- cotransporter, DIOA (100 and 500 μM), diminished the cell proliferation. NPPB (100 and 300 μM, a blocker of Cl- channel) and quinine (100 and 500 μM, a blocker of K+ channel) also suppressed the proliferation of MC3T3-E1 cells. These blockers of the K+/Cl- cotransporter/channels (DIOA, NPPB and quinine) would increase the intracellular Cl- concentration ([Cl-]i). On the other hand, our previous study (Biochem. Biophys. Res. Commun. 361, 1038-1043, 2007) reported that a decrease in [Cl-]i diminished the proliferation of MC3T3-E1 osteoblastic cells. Taken together, the observations indicate that both increases and decreases in [Cl-]i diminish the proliferation of MC3T3-E1 osteoblastic cells.
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