UMIN000012537.

Elucidation of the mechanisms underlying neuropathic pain is expected to aid in the discovery and selection of effective therapeutic methods. Currently, microRNA (miRNA) is thought to play an important role in the development and maintenance of the nervous system. We, therefore, hypothesized that miRNAs are involved in neuropathic pain, and investigated this possibility by analyzing miRNA expression in the dorsal horn of the spinal cord in a chronic constriction injury (CCI) rat model using the TaqMan® Low Density Array (TLDA). Neuropathic pain model rats were produced by CCI induced by ligation of the sciatic nerve. The miRNA expression in the dorsal horn of the spinal cord was analyzed in Day 0 rats, with no sciatic nerve ligation or sham operation, Day 7 rats, examined 7 days after sciatic nerve ligation or sham operation, and Day 14 rats, examined 14 days after sciatic nerve ligation or sham operation using TLDA. In this study, 111 miRNAs were significantly regulated in CCI rats in both the Day 7 and Day 14 groups compared with sham rats in both groups. Of these 111, there were 75 miRNAs (67.6%) that had been analyzed in previous reports and 36 miRNAs (32.4%) related to the development of tumors of the nervous system and neurodegenerative diseases. Certain miRNAs were reported to be related to neuropathic pain; miR-500, -221 and -21. The expression levels of a large number of miRNAs in the dorsal horn of the spinal cord in CCI rats changed. These results provide a step toward elucidation of the mechanisms underlying neuropathic pain.

Dexmedetomidine hydrochloride is a potent, highly selective alpha-2 adrenergic receptor agonist, broadly used as a sedative drug in intensive care units. We describe the case of a 59-yr-old patient who experienced drug fever caused by dexmedetomidine hydrochloride. The patient was transferred to the intensive care unit with an abdominal aortic aneurysm rupture. After initiation of sedation with dexmedetomidine hydrochloride, he developed pyrexia of more than 39 degrees C. This symptom improved rapidly 7 h after stopping dexmedetomidine hydrochloride. Other possible causes (such as infection) were sequentially eliminated.

The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical Helicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested.It is well known that Helicobacter pylori is associated with gastric disorders, such as gastritis, and the gastric or duodenal ulcer (2,5,8,15,21). The combination chemotherapy, i.e., amoxicillin (AMC) plus clarithromycin (CAM) or metronidazole (MNZ) with a proton pump inhibitor (PPI) is now widely recommended for eradication chemotherapy (1,3,4,6,9,13,14,16 ATPase, and preliminary studies demonstrate that RPZ produces a potent and long-lasting inhibition of gastric acid secretion and a low level of hypergastrinemia (3,17,20). A novel RPZ demonstrating a chemical structure of C 18 H 20 N 3 SNa with a molecular weight of 381.43, as shown in Fig. 1, was developed in 1997 and has been proven to be effective against H. pylori strains, like other PPIs, such as lansoprazole (LPZ) and omeprazole (OPZ) (11,19). It has been demonstrated to act as an irreversible noncompetitive inhibitor of the enzyme urease that is an important virulence factor of pathogenicity of gastric H. pylori (17,20). The in vivo evaluation study of RPZ has recently been reported (18). However, no in vitro data has been available to date concerning the interaction studies of RPZ in combination with some kinds of antibiotics. Therefore, we tried to evaluate its bactericidal activity when combined with an antibiotic compound against H. pylori strains by the time-kill curve assay (10). We at first determined the in vitro activities of RPZ and its thioether (TH) derivative, RPZ-TH, together with OPZ and LPZ.The 133 H. pylori strains tested were recent clinical isolates from different patients with chronic gastritis and gastric and/or duodenal ulcer during the 2 years between April 1996 and March 1998, at the Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan. In addition, two reference strains, H. pylori NCTC 11637 and NCTC 11916, were also included in this study. All of the strains examined were preserved in Microbank (Pro-Lab Diagnostic, Richmond Hill, Ontario, Canada) vials in a deep freezer at Ϫ83°C.The antimicrobials and PPIs used were as follows: AMC from Meiji Seika Kaisha, Ltd., Tokyo, Japan; CAM from Taisho Pharmaceuticals, Co., Ltd., Tokyo, Japan; MNZ from Shionogi & Co., Ltd., Tokyo, Japan; RPZ and its derivative, RPZ-TH, from Eisai Pharmaceuticals Co., Ltd, Tokyo, Japan; LPZ from Takeda Chemical Industries, Ltd., Osaka, Japan; and OPZ from Astra Japan Ltd., Tokyo, Japan.In determining the MICs, twofold serial dilutions of each drug were made in 50 l of brucella broth (BBL Microbiology Systems Inc., Cockey...

Hydrazine derivatives of several pyrazolo[1,5-alpha]pyrimidines (A), pyrazolo[1,5-alpha]-1,3,5-triazines (B), s-triazolo[1,5-alpha]pyrimidines (C), and imidazo[1,2-alpha]pyrimidines (D) were synthesized and condensed with 5-nitrofurfural in order to obtain the corresponding nitrofurfural hydrazones of each heterocycle (1d-14d). Each compound was screened for in vitro activity against Trypanosoma cruzi. The compounds were then tested in vivo against experimental infections of T. cruzi in laboratory (C3H/He strain) mice. An interesting structure-activity relationship was uncovered, revealing that 5-methyl-7-(5-nitrofurfurylidenehydrazino)pyrazolo[1,5-alpha]pyrimidine (2d) greatly increased the mean survival time (IMST) of mice with terminal infections. Subtle alterations in the structure of 2d, such as the substitution of a 5-hydrogen for the 5-methyl group (1d) or the substitution of the 3-hydrogen by the water-soluble 3-sulfonic acid (3d) or 3-sodium sulfonate (4d), resulted in a drastic loss of in vivo and in vitro activity.