Objective: To compare effects of the fluoropyrimidines S-1 and capecitabine on prothrombin time international normalized ratios (PT-INR) of warfarin following coadministration and after discontinuation of each fluoropyrimidine treatment.
Methods: Medical records of patients receiving warfarin with either S-1 (6 patients) or capecitabine (7 patients) were obtained from four hospitals.
Results: Increased PT-INR was observed until peak levels of warfarin were achieved in all patients in S-1 and capecitabine treatment groups.　Moreover, PT-INR significantly changed after coadministration within each group (p＜0.05).　Specifically, ratios of peak PT-INR after coadministration of each fluoropyrimidine and those following administration of warfarin alone (PT-INR elevation ratio) were 3.31 and 3.29 in S-1 and capecitabine coadministration groups, respectively.　Moreover, numbers of days to peak PT-INR were 38.3 and 31.3 days, respectively, and did not significantly differ between the treatment groups.　Furthermore, PT-INR returned to pretreatment levels by 17.5 and 15.1 days after discontinuation of S-1 and capecitabine, respectively, and did not significantly differ between the treatment groups.
Conclusion: Coadministration of S-1 and capecitabine similarly prolongs PT-INR by approximately 3-fold compared with administration of warfarin alone; therefore, these drug-drug interactions were clinically suggested to be of high risk for episodes of bleeding and remarkable alterations in coagulation parameters.　Therefore, blood coagulation ability should be more carefully monitored with regard to PT-INRs in patients receiving warfarin with S-1 or capecitabine not only during coadministration but also after discontinuation of fluoropyrimidine treatments.

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Animals ; Calcitonin/*pharmacology ; Cell Line ; Connective Tissue Growth Factor/*genetics/metabolism ; Female ; Kidney Tubules, Proximal/*enzymology/metabolism ; *MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Phosphorylation ; Swine

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Animals ; Calcitonin/*pharmacology ; Cell Line ; Connective Tissue Growth Factor/*genetics/metabolism ; Female ; Kidney Tubules, Proximal/*enzymology/metabolism ; *MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Phosphorylation ; Swine

STUDY DESIGN: Retrospective study. PURPOSE: To investigate the relationship between preoperative total spinal sagittal alignment and the early onset of adjacent segment degeneration (ASD) after single-level posterior lumbar interbody fusion (PLIF) in patients with normal sagittal spinal alignment. OVERVIEW OF LITERATURE: Postoperative early-onset ASD is one of the complications after L4–L5 PLIF, a common surgical procedure for lumbar degenerative disease in patents without severe sagittal imbalance. A better understanding of the preoperative characteristics of total spinal sagittal alignment associated with early-onset ASD could help prevent the condition. METHODS: The study included 70 consecutive patients diagnosed with lumbar degenerative disease who underwent single-level L4–L5 PLIF between 2011 and 2015. They were divided into two groups based on the radiographic progression of L3–L4 degeneration after 1-year follow-up: the ASD and the non-ASD (NASD) group. The following radiographic parameters were preoperatively and postoperatively measured: sagittal vertebral axis (SVA), thoracic kyphosis (TK), lumbar lordosis, pelvic tilt, and pelvic incidence (PI). RESULTS: Eight of the 70 patients (11%) experienced ASD after PLIF (three males and five females; age, 64.4±7.7 years). The NASD group comprised 20 males and 42 females (age, 67.7±9.3 years). Six patients of the ASD group showed decreased L3–L4 disc height, one had L3–L4 local kyphosis, and one showed both changes. Preoperative SVA, PI, and TK were significantly smaller in the ASD group than in the NASD group (p <0.05). CONCLUSIONS: A preoperative small SVA and TK with small PI were the characteristic alignments for the risk of early-onset ASD in patients without preoperative severe sagittal spinal imbalance undergoing L4–L5 single-level PLIF.
Animals ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kyphosis ; Lordosis ; Male ; Retrospective Studies

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Objective: In order to ensure the safety of nursing home residents, it is very important to implement appropriate assistance to ensure compliance with necessary medication. The purpose of this study is to identify issues and to plan solutions for medication assistance.Design: We conducted a workshop involving care workers (CWs), nurses and pharmacists together.Methods: Using the KJ method, participants extracted problems related to medication assistance and planned solutions in a mixed group of CWs, nurses and pharmacists. Questionnaire surveys were conducted for the participants before, immediately after, and 3 months after the workshop.Results: A number of important and urgent issues related to medication assistance were identified. There were differences in the recognition patterns of the importance and urgency of the issues among the three categories of participants. In addition, many possible solutions were proposed. Among these solutions, 25% had been implemented by at least two participants. More than 75 % of participants felt that their awareness of the value of cooperation in medication assistance had been improved by participating in the workshop.Conclusion: These results suggest that a workshop with a group of CWs, nurses and pharmacists in one place is a useful approach for extracting problems and planning effective solutions related to cooperation in medication assistance.