Adrenaline increases the rate of cross-bridge cycling in rat cardiac muscle

To characterize the myocardial cross-bridge dynamics in catecholamine-induced positive inotropic state, we studied the effects of adrenaline (6 X 10(-6) M) on the transient central segment length (SL) response to step decrease in tension in rat right ventricular papillary muscle in barium contracture. The time course of this response is thought to reflect the kinetics of actin-myosin interaction. The muscle was released stepwise from the steady contracture tension (Tc) to new steady tension levels (Tr) of varying magnitudes at 22 degrees C. When the tension decrease was less than 0.7 Tc, the SL transient responses comprised, in most cases, four phases. The first phase was a rapid and minute shortening during tension reduction; the second was a slow further shortening; the third, a slow lengthening; and the fourth, an extremely slow shortening toward a new steady length under the new tension. Adrenaline showed almost no effect on Tc and the amplitude of SL transients, but markedly reduced the duration of the second (D2) and third (D3) phases of SL transient regardless of the amplitude of tension reduction. The reduction of duration was 14 +/- 3% in D2 and 26 +/- 5% in D3 at Tr/Tc of 0.84 +/- 0.03 on the average (mean +/- S.D.) in nine preparations. The velocity measured from the quasi-steady SL shortening in the second phase increased with the addition of adrenaline, regardless of the amplitude of tension reduction. The increase in the shortening velocity was 16 +/- 6% (mean +/- S.D., n = 9) at Tr/Tc of 0.18 +/- 0.04. These results suggest that adrenaline increases the rate of cross-bridge cycling in cardiac muscle independent of activation level.     

The Use of a Circular Side Stapling Technique in Laparoscopic Low Anterior Resection for Rectal Cancer: Experience of 30 Serial Cases

The double-stapling technique using a circular stapler (CS) to create an end-to-end anastomosis is currently used widely in laparoscopic-assisted rectal surgery. However, a high rate of anastomotic failure has been reported. We report new side-to-side anastomosis creation using a CS, the so-called circular side stapling technique (CST). After excising the rectum at the oral and anal sides of the tumor with a linear stapler, a side-to-side colorectal anastomosis was made on the anterior wall of the rectosigmoid colon and the anterior or posterior wall of the rectum with a CS. Between 2012 and 2013, we recorded 30 serial cases of rectal-sigmoid or rectal cancer that were treated with laparoscopic-assisted surgeries using this method. In the 30 cases, the mean age was 68 ± 12 years, operating time was 288 ± 80 minutes, and blood loss was 66 ± 67 mL. None of the patients suffered from anastomosis leakage or postoperative anastomotic bleeding, and none complained of their stool habits. Three months after the last surgery in this cohort, no anastomosis strictures were reported. Based on these results, we propose an alternative method of side-to-side anastomosis for low anterior resection by using a CS to prevent staple overlap. Our experience indicates that the CST is easy and safe. Therefore, this method is a useful alternative to the current method used in laparoscopic surgery.Key words: Laparoscopy, Circular stapler, Colorectal cancer, Low anterior resectionLaparoscopic surgery for the treatment of colorectal disease has proven to be a safe and effective method compared with an open procedure.^1–3 Laparoscopy has the advantages of reduced blood loss, hospital stay, and use of anesthetics as well as a better cosmetic outcome. Although many clinical studies have demonstrated the advantages and low complication rates of laparoscopic colectomy and low anterior resection,^1–5 a high rate of anastomotic leakage has been reported in laparoscopic rectal surgeries. The reported incidence of leakage after laparoscopic surgery for the treatment of rectum varies from 6% to 17%.^1–3 Additionally, anastomotic leakage might raise concerns about local recurrence and may limit the patients prognosis.^6–8 Therefore, despite great advances in laparoscopic surgery, the risks of anastomotic complications persist to a greater extent than those for other colonic resections.^6,7Recent reports have included proposed methods for reducing anastomotic leakage, and recently a transanal drainage tube has been recommended, because the high pressure experienced in the rectum could cause anastomotic failure.⁹ Another group reported the use of anti-traction sutures supporting the anastomosis to reduce anastomotic leakage.¹⁰ Despite these proposals, anastomotic failure has not been completely resolved.In typical laparoscopic rectal surgery, a double-stapling technique (DST) with a circular stapler is used to create the anastomosis. This method is thought to be the only method available to complete an intracorporeal anastomosis of the rectum. However, the DST requires the excision of the stump of the staple line created by the linear stapler. Our previous endoscopic experience with anastomotic leakage shows that leakage occurs frequently at the point where the staples overlap in the DST.¹¹ In this study we demonstrate a new circular side stapling technique (CST), which does not require the excision of the linear staple line in a laparoscopic low anterior resection.     

Studies on the mechanism of accumulation of cholesterol in the gallbladder mucosa. Evidence that sterol 27-hydroxylase is not a pathogenetic factor

BACKGROUND/AIMS: Cholesterolosis is characterized by accumulation of esterified cholesterol in human gallbladder mucosa. The present study aimed at investigating possible pathogenetic factors for cholesterolosis. The hypothesis was tested that a reduced sterol 27-hydroxylase or an increased amount of ACAT-1 enzyme may be of importance. METHODS: Gall bladder mucosa and bile were obtained from patients with cholesterol gallstones undergoing cholecystectomy (30 with and 43 without cholesterolosis). RESULTS: In cholesterolosis, the gall bladder mucosa was characterized by a several-fold increase in esterified cholesterol and normal content of free cholesterol. The amount of ACAT-1 protein, measured by immunoblotting, was similar in patients with and without cholesterolosis. The level of 27-hydroxycholesterol in gallbladder mucosa was elevated sevenfold as compared with cholesterol in patients with cholesterolosis. Most (87%) of this oxysterol was esterified and the accumulation is most probably secondary to the higher total amount of cholesterol in the cells. Patients with cholesterolosis had normal levels of both sterol 27-hydroxylase mRNA (real time polymerase chain reaction) and protein (immunoblotting). The enzymatic activity of the sterol 27-hydroxylase in gallbladder mucosa was normal or increased in cholesterolosis. CONCLUSIONS: The pathogenesis of cholesterolosis may be multifactorial, but is not caused by reduced efflux of cholesterol due to a defect sterol 27-hydroxylase mechanism.     

Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine.

BACKGROUND. We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent. To examine this hypothesis, we compared the effects of pimobendan and dobutamine on left ventricular contractility and energetics using the frameworks of Emax (contractility index) and the relation between VO2 and PVA (systolic pressure-volume area, a measure of left ventricular total mechanical energy). METHODS AND RESULTS. We measured VO2, Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing dog hearts. The slope of the VO2-PVA relation reciprocally indicates the efficiency from PVA-dependent VO2 to the total mechanical energy (contractile efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent VO2, reflects energy utilization for excitation-contraction coupling. The ratio of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs comparably enhanced Emax. Although the contractile economy was greater by 14 +/- 19% (p less than 0.05) for pimobendan than for dobutamine, the contractile efficiency was similar between the two drugs. Oxygen cost of contractility, defined as the slope of the relation between the PVA-independent VO2 and Emax, was the same between the two drugs. Other mechanoenergetic effects of both drugs were similar except for a greater coronary vasodilating effect of pimobendan. CONCLUSIONS. Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation. The calcium-sensitizing effect of pimobendan did not save the oxygen cost of contractility.     

Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis: possible involvement of osteopontin in bone destruction in arthritis

OBJECTIVE: To investigate the involvement of osteopontin (OPN) in bone destruction in a murine experimental arthritis model of collagen-induced arthritis (CIA). METHODS: The expression of OPN was examined at both the messenger RNA (mRNA) and protein levels in various arthritic lesions in mice with CIA by in situ hybridization and immunohistochemistry, respectively. In addition, the expression of alpha(v)beta3 integrin, a receptor for OPN, the ligation of which is thought to be essential for bone resorption by osteoclasts, was examined by immunohistochemistry. Plasma concentrations of OPN were measured at different time points in the course of CIA by enzyme-linked immunosorbent assay. RESULTS: OPN mRNA was detected mainly at sites of bone erosion in arthritic lesions, where activated osteoclasts were present; OPN protein was also detected at sites of bone erosion. In the arthritic synovium, OPN was predominantly expressed in the synovial lining layer, but not in lymphoid aggregates. In addition, alpha(v)beta3 integrin was detected coincident with OPN at sites of bone erosion (bone-pannus junction). Plasma OPN levels were markedly elevated at the time points that corresponded to arthritis flares, and higher levels were maintained during the progression of arthritis. CONCLUSION: OPN may mediate bone resorption by osteoclasts in arthritis through ligation with its receptor, alpha(v)beta3 integrin. OPN may be a useful therapeutic target molecule in the prevention of bone destruction in arthritis.     

Relationship between navicular drop and measuring position of maximal plantar flexion torque of the first and second-fifth metatarsophalangeal joints

[Purpose] The purpose of this study was to determine the relationship between navicular drop and plantar flexion torque of the first and second-fifth metatarsophalangeal joints. [Subjects] Ten healthy young men participated in this study. [Methods] The Pearson product-moment correlation coefficient was calculated to determine the relationship between navicular drop and plantar flexion torque of the first and second-fifth metatarsophalangeal joints. [Results] Significant negative correlations were observed between navicular drop and plantar flexion torques in the lengthened position of the intrinsic toe plantar flexion muscles, but no correlations were found between navicular drop and plantar flexion torques in the neutral position of the ankle and metatarsophalangeal joints. Moreover, the intrinsic toe plantar flexion muscles were found to contribute to the formation of the medial longitudinal arch. [Conclusion] Navicular drop correlates with metatarsophalangeal joint muscle strength in plantar flexion where the intrinsic toe muscles are capable of exerting force.Key words: Toe flexor strength, Intrinsic foot muscle, Medial longitudinal arch