Involvement of TRPV3 and TRPM8 ion channel proteins in induction of mammalian cold-inducible proteins

Cold-inducible RNA-binding protein (CIRP), RNA-binding motif protein 3 (RBM3) and serine and arginine rich splicing factor 5 (SRSF5) are RNA-binding proteins that are transcriptionally upregulated in response to moderately low temperatures and a variety of cellular stresses in mammalian cells. Induction of these cold-inducible proteins (CIPs) is dependent on transient receptor potential (TRP) V4 channel protein, but seems independent of its ion channel activity. We herein report that in addition to TRPV4, TRPV3 and TRPM8 are necessary for the induction of CIPs. We established cell lines from the lung of TRPV4-knockout (KO) mouse, and observed induction of CIPs in them by western blot analysis. A TRPV4 antagonist RN1734 suppressed the induction in wild-type mouse cells, but not in TRPV4-KO cells. A TRPV3 channel blocker S408271 and a TRPM8 channel blocker AMTB as well as siRNAs against TRPV3 and TRPM8 suppressed the CIP induction in mouse TRPV4-KO cells and human U-2 OS cells. A TRPV3 channel agonist 2-APB induced CIP expression, but camphor did not. Neither did a TRPM8 channel agonist WS-12. These results suggest that TRPV4, TRPV3 and TRPM8 proteins, but not their ion channel activities are necessary for the induction of CIPs at 32 °C. Identification of proteins that differentially interact with these TRP channels at 37 °C and 32 °C would help elucidate the underlying mechanisms of CIP induction by hypothermia

Serum Level of Hyaluronic Acid Does not Correlate with Changes of Hepatic Volume after Portal Vein Embolization

The serum hyaluronic acid (HA) levels are associated with liver regeneration after hepatectomy. In the present study, the HA concentrations were examined to evaluate the relationship with changes of hepatic volume after right portal vein embolization (PVE). The HA level of serum samples from 10 patients who underwent PVE before hepatectomy of the right lobe was measured, and the results were compared to the changed volume of embolized right lobe and unembolized left lobe of the liver. The mean serum HA level in patients with chronic viral liver disease (CVLD) (202+/-118 ng/ml) was significantly greater than in those without CVLD (70+/-24 ng/ml) (p<0.05). The volume of embolized liver decreased 72+/-96 CM3 (-8.9+/-5.5 %), while the volume of unembolized liver increased 106+/-67 CM3 (+8.9+/-5.5 %) 2 weeks after PVE. HA concentrations after 2 weeks of PVE (296+/-216 ng/ml) tended to be greater than that before PVE (134+/-108 ng/ml) but not statistically significant (p=0.105). There were no correlations between serum HA levels before PVE and the changes of hepatic volume in embolized and unembolized lobe after PVE. Our results indicate that the measurement of HA level is not useful for predicting the effect of PVE

Relationship between the Immunohistochemical Expressions of Cathepsin B, Laminin and Tenascin and Clinicopathologic Features in Gallbladder Carcinomas

In the present study, the expression of protease indicated by cathepsin B (CB) and the expression of extracellular matrix indicated by laminin (LN) and tenascin (TN) was immunohistochemically examined in 25 gallbladder carcinomas. The incidence of expression of .CB and TN in normal epithelium was 1/25 (4%) and 0/25 (0%), respectively, and significantly increased in carcinomas (14/25 : 56% and 21/25 : 84%, respectively) (p<0.01). The LN expression was detected in the basement membrane of all normal epithelium, and the incidence of LN expression was significantly decreased in the carcinomas (7/25: 28%) (p<0.01). The incidence of CB expression in poorly differentiated adenocarcinomas (1/8: 13%) was significantly lower than that in papillary, welland moderately differentiated adenocarcinomas (11/15: 74%) (p<0.01). However, these responses were not significantly related with other histologic features or nuclear DNA ploidy pattern. The LN expression of the hepatic metastasis group (4/6 :67%) was significantly greater than that in the non-metastatic group (3/19 :16%) (p<0.05). The expressions of CB, LN and TN were not associated with the postoperative prognosis. In conclusion, the increased expressions of CB and TN, and the decreased expression of LN were cancerassociated alterations. The expression of CB was correlated with the histological grade of differentiation, and the expression of LN was correlated with the hepatic metastasis

An Immunohistochemical Study of Tumor Vascularity and Proliferation Activity in Cholangiocellular Carcinoma: Relationship to Clinicopathologic Factors and Prognosis after Hepatic Resection

This study was designed to provide an immunohistochemical analysis of tumor biological factors in 28 patients who underwent hepatectomy for cholangiocellular carcinoma (CCC). Analyzed factors were microvessel counts (stained by CD34) and proliferating cell nuclear antigen (PCNA). PCNA L.I. was correlated with serum level of CA19-9, which was correlated with a higher recurrence rate and shorter patient survivals. Microvessel counts were negatively correlated with tumor size. Furthermore, the microvessel count in CCC with mass-forming (MF) plus periductal infiltrating (PI) type associated with poorer survivals, was significantly lower compared to that of CCC with MF type or PI type. Neither microvessel counts nor PCNA L.I. were associated with any other clinicopathologic factors or cancer recurrence. The five-year overall and cancer-free survival rates were 26% and 13%, respectively. Patients with MF plus PI type, poorer differentiated carcinoma, stage 4A and higher CA19-9 level had shorter cancer-free and overall survivals after hepatectomy (p<0.05). Cancer-free and overall survivals in patients with lower microvessel counts tended to be slightly worse but were not significantly different. Although tumor microvessel count and proliferating activity were correlated with prognostic clinicopathologic parameters, both factors might not be prognostic markers for predicting CCC recurrence and patient survival

Treatment of Surgical Site Infection with Aqua Oxidation Water: Comparison with Povidone Iodine

Aqua oxidation water is a new disinfectant with a bactericidal activity based on high oxidation-reduction potential and acidity. We compared the effectiveness of aqua oxidation water and povidone iodine against the surgical site infection (SSI). The bacteriological effect against several organisms and the efficacy of both disinfectants were almost similar. However, the duration of treatment with aqua oxidation water was shorter than that with the povidone iodine in healed wounds (p<0.05) and the number of patients treated with aqua oxidation water who reported pain was smaller than that with povidone iodine (p<0.05). Our results indicated that aqua oxidation water useful and effective for the treatment of incurable SSI

Resected or Remnant Liver Volume and Standard Liver Volume Ratio in Patients with Major Hepatectomy

To clarify the relationship between resected (RSV) or remnant hepatic volume (RMV) in major hepatectomy, and standard liver volume (SLV) and its clinical significance, the RSV/SLV, RMV/SLV and the volume of regeneration (RGV)/RMV were examined in 41 patients including 19 with chronic hepatitis and 5 with obstructive jaundice who underwent lobectomy or extended lobectomy. The hepatic function was maintained in all patients. SLV was calculated by the body-surface area using Urata\u27s formula. RGV was calculated by subtracting the RMV from the remnant liver volume at day 28 after hemi-hepatectomy. Measurement of the hepatic volume was performed by computed tomography. The means of RSV, RMV, RGV and SLV were 591 ﾂｱ 173, 459 ﾂｱ 119, 667 ﾂｱ 129 and 1128 ﾂｱ 129cm3, respectively. The means of RSV/SLV, RMV/SLV and RGV/RMV were 0.52 ﾂｱ 0.14, 0.41 ﾂｱ 0.12 and 1.54 ﾂｱ 0.47, respectively. RGV was inversely correlated with RMV/SLV (p<0.001) but not with the other parameters. RSV/SLV and RMV/SLV were not associated with long-term ascites and hepatic failure. The tendency of these results was similar in each patient with a normal liver, obstructive jaundice and chronic viral hepatitis. If the hepatic functional reserve is maintained, a liver with lower hepatic volume has potentially sufficient regeneration even in patients with an injured liver

Low-Intensity Resistance Training with Moderate Blood Flow Restriction Appears Safe and Increases Skeletal Muscle Strength and Size in Cardiovascular Surgery Patients:A Pilot Study

We examined the safety and the effects of low-intensity resistance training (RT) with moderate blood flow restriction (KAATSU RT) on muscle strength and size in patients early after cardiac surgery. Cardiac patients (age 69.6 +/- 12.6 years, n = 21, M = 18) were randomly assigned to the control (n = 10) and the KAATSU RT group (n = 11). All patients had received a standard aerobic cardiac rehabilitation program. The KAATSU RT group additionally executed low-intensity leg extension and leg press exercises with moderate blood flow restriction twice a week for 3 months. RT-intensity and volume were increased gradually. We evaluated the anterior mid-thigh thickness (MTH), skeletal muscle mass index (SMI), handgrip strength, knee extensor strength, and walking speed at baseline, 5-7 days after cardiac surgery, and after 3 months. A physician monitored the electrocardiogram, rate of perceived exertion, and the color of the lower limbs during KAATSU RT. Creatine phosphokinase (CPK) and D-dimer were measured at baseline and after 3 months. There were no side effects during KAATSU RT. CPK and D-dimer were normal after 3 months. MTH, SMI, walking speed, and knee extensor strength increased after 3 months with KAATSU RT compared with baseline. Relatively low vs. high physical functioning patients tended to increase physical function more after 3 months with KAATSU RT. Low-intensity KAATSU RT as an adjuvant to standard cardiac rehabilitation can safely increase skeletal muscle strength and size in cardiovascular surgery patients.</p

Spontaneous Closure of a Rectovaginal Fistula that Developed after Double-stapled Anastomosis in Low Anterior Resection

Management of a rectovaginal fistula (RVF) following low circular-stapled colorectal anastomosis is difficult and often unsatisfactory. We report herein the case of a 66- year-old woman who developed a RVF following low anterior resection using the double-stapling technique for rectal cancer. The RVF spontaneously closed with nonoperative treatment that included simple observation without dietary restrictions. The spontaneous closure occurred within approximately 25 days. Minimally symptomatic patients may be candidates for nonoperative treatment