Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

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Effects of cicletanine on the urinary excretion of prostanoids and kallikrein,and on renal function in man

Summary The effects of cicletanine, a new antihypertensive agent, on the prostaglandin-kallikrein system and the reninangiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F₁ was enhanced significantly, urinary excretion of thromboxane-B₂, prostaglandin-E₂, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A₂. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed.     

Laparoscopic ventral rectopexy in patients with fecal incontinence associated with rectoanal intussusception: prospective evaluation of clinical,physiological and morphological changes

Background

Physiological changes after laparoscopic ventral rectopexy (LVR) in patients with rectoanal intussusception (RAI) remain unclear. This study was undertaken to evaluate physiological and morphological changes after LVR for RAI, and to study clinical outcomes following LVR with special reference to fecal incontinence (FI).

Methods

The study was conducted on patients who had LVR for RAI between February 2012 and December 2016 at our institution Patients with RAI and FI were included in the study. Patients with RAI and obstructed defecation and those with RAI and neurologic FI were not included. The patients had anorectal manometry preoperatively, and 3, 6, and 12 months postoperatively. Defecography was performed before and 6 months after the procedure. FI was evaluated using the Fecal Incontinence Severity Index (FISI).

Results

There were 34 patients (median age 77 years (range 60–93) years). Thirty-two patients (94%) were female and the median number of vaginal deliveries was 2 (range 0–5). Neither maximum resting pressure nor maximum squeeze pressure increased postoperatively. There was an overall increase in both defecatory desire volume (median preoperative 75 ml vs. 90 ml at 12 months; p?=?0.002) and maximum tolerated volume (median preoperative 145 ml vs.175 ml at 12 months; p?=?0.002). Postoperatively, RAI was eliminated in all patients but one, although 13 had residual rectorectal intussusception found at defecography. There was an overall reduction in both rectocele size (median preop 29 mm vs. postop 10 mm; p?=?0.008) and pelvic floor descent (median preop 26 mm vs. postop 20 mm; p?=?0.005). Twelve months after surgery, a reduction of at least 50% was observed in the FISI score for 31 incontinent patients (91%).

Conclusions

LVR for RAI produced adequate improvement of FI, and successful anatomical correction of RAI was confirmed by postoperative proctography. Postoperative increase in the rectal volume may have a positive effect on continence.

     

Large conformational changes of the epsilon subunit in the bacterial F1F0 ATP synthase provide a ratchet action to regulate this rotary motor enzyme

The F(1)F(0) ATP synthase is the smallest motor enzyme known. Previous studies had established that the central stalk, made of the gamma and epsilon subunits in the F(1) part and c subunit ring in the F(0) part, rotates relative to a stator composed of alpha(3)beta(3)deltaab(2) during ATP hydrolysis and synthesis. How this rotation is regulated has been less clear. Here, we show that the epsilon subunit plays a key role by acting as a switch of this motor. Two different arrangements of the epsilon subunit have been visualized recently. The first has been observed in beef heart mitochondrial F(1)-ATPase where the C-terminal portion is arranged as a two-alpha-helix hairpin structure that extends away from the alpha(3)beta(3) region, and toward the position of the c subunit ring in the intact F(1)F(0). The second arrangement was observed in a structure determination of a complex of the gamma and epsilon subunits of the Escherichia coli F(1)-ATPase. In this, the two C-terminal helices are apart and extend along the gamma to interact with the alpha and beta subunits in the intact complex. We have been able to trap these two arrangements by cross-linking after introducing appropriate Cys residues in E. coli F(1)F(0), confirming that both conformations of the epsilon subunit exist in the enzyme complex. With the C-terminal domain of epsilon toward the F(0), ATP hydrolysis is activated, but the enzyme is fully coupled in both ATP hydrolysis and synthesis. With the C-terminal domain toward the F(1) part, ATP hydrolysis is inhibited and yet the enzyme is fully functional in ATP synthesis; i.e., it works in one direction only. These results help explain the inhibitory action of the epsilon subunit in the F(1)F(0) complex and argue for a ratchet function of this subunit.     

Serum heart-type fatty acid binding protein predicts cardiac events in elderly patients with chronic heart failure

BACKGROUND AND OBJECTIVES: Heart-type fatty acid binding protein (H-FABP) is released into the circulation from the damaged myocardium of patients with severe chronic heart failure. Chronic heart failure is the most frequent cause of death and disability in the elderly. However, there are no data for the prognostic value of H-FABP in the elderly population. This study investigated whether H-FABP can effectively predict the prognosis in elderly patients (> or = 70 years) with chronic heart failure. METHODS: Serum H-FABP levels were measured in 90 chronic heart failure patients > or =70 years old (mean age 77 +/- 4 years, range 70-92 years), and patients were followed-up for 421 +/- 326 days. RESULTS: There were 35 cardiac events (38.9%) including cardiac deaths and readmissions for worsening chronic heart failure. Multivariate analysis with the Cox proportional hazard model showed that H-FABP was the only independent predictor of cardiac events (chi2 = 6.640, p = 0.0100). Kaplan-Meier analysis revealed that H-FABP effectively risk stratified elderly patients with chronic heart failure for cardiac events. CONCLUSIONS: These findings suggest that H-FABP is a reliable marker for prognosis in elderly patients with chronic heart failure.     

Clinical Effectiveness of Tolvaptan in Patients with Acute Decompensated Heart Failure and Renal Failure: Design and Rationale of the AQUAMARINE Study

Purpose

Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment.

Methods

The Answering question on tolvaptan’s efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m² will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide.

Conclusion

This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109).