Increase in ovarian 15-hydroxyeicosatetraenoic acid during ovulation in the gonadotropin-primed immature rat

The ovarian level of 15-hydroxyeicosatetraenoic acid (15-HETE) was measured by RIA during ovulation in gonadotropin-primed immature Wistar rats. The ovulatory process was initiated in 25-day-old rats by a 10-IU injection of hCG sc 2 days after the animals had been primed with 10 IU PMSG, sc. Ovarian follicles begin to ovulate 10 h after hCG. At 0 h after hCG, the ovarian 15-HETE level was 0.6 +/- 0.2 ng/mg ovarian protein. At 6 h the 15-HETE level increased sharply to 27.3 +/- 4.2 ng/mg protein and reached a peak of 50.0 +/- 9.8 ng/mg protein at 10 h. Ovarian 15-HETE decreased significantly between 10-16 h after hCG (when ovulation was essentially completed). The pattern of secretion of this 15-lipoxygenase product was reciprocal to the pattern of secretion of leukotriene-B4 by the rat ovary. Ovarian 15-HETE production and ovulation were inhibited in a dose-dependent manner when indomethacin was administered sc 1 h after hCG in doses ranging from 0.10-10.0 mg/rat. In contrast, the synthesis of ovarian prostaglandins-E and -F was inhibited by a dose of indomethacin as low as 0.0316 mg/rat, but this dose did not significantly affect the ovarian 15-HETE level or the ovulation rate. Therefore, the ovulation rate was more closely correlated with the ovarian 15-HETE level (P less than 0.001) than with the ovarian levels of either prostaglandin-E or -F (0.10 greater than P greater than 0.05). The results suggest that products of the 15-lipoxygenase pathway of arachidonic acid metabolism may be important in the biochemical events of mammalian ovulation.     

New canine model of chronic pancreatitis due to chronic ischemia with incomplete pancreatic duct obstruction

A new experimental model of chronic pancreatitis was produced by a combination of chronic ischemia and incomplete obstruction of the pancreatic duct. Ischemia was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Incomplete ductal obstruction was achieved by ligation and separation of the minor pancreatic duct and placement of a polyethylene tube in the major pancreatic duct. Macroscopic examination at 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin test, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. Pancreatography revealed dilatation and meandering of the major pancreatic duct and poor visualization of its secondary and tertiary bifurcations. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. This model most closely resembles human chronic pancreatitis, and is a very useful instrument.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

The effect of an elemental diet on oral mucositis of esophageal cancer patients treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC study)

Purpose

Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy.

Methods

We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system.

Results

Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade?≥?2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p?=?0.046).

Conclusions

An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study.

Clinical trial

The date of submission: Dec 08th, 2017.

     

Effects of drug, biobehavioral and exercise therapies on heart rate variability in coronary artery disease: a systematic review

BACKGROUND: Heart rate variability (HRV) is reported as a surrogate index for clinical outcome in trials of secondary prevention strategies for coronary artery disease (CAD), but a standardized guide for interpreting HRV change is not established. DESIGN: We evaluated HRV change in trials with CAD patients who received conventional medications (beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors), biobehavioral treatment (psychotropics, biofeedback, relaxation) or exercise training. METHODS: Medline, Pubmed, Psycinfo, the Cochrane database, and Embase were searched until July 2007, without language restriction. We identified 33 randomized controlled trials. Two reviewers independently abstracted all trials using a standardized form. A hierarchy of frequency and time domain HRV indices defined outcome. RESULTS: A random-effects model yielded an overall pooled standardized mean difference (SMD) between treatment and control groups of moderate magnitude across treatment classes, based on a composite of time and frequency domain indices (SMD=0.40, P<0.0001), or only time or frequency indices (SMD=0.37 and 0.43, respectively, both P<0.0001). This change was equivalent to an increase in standard deviation of all normal-to-normal RR intervals of 9.0 ms (95% Confidence Interval, CI, 7.3, 10.7 ms) or a relative increase of 15.9% (95% CI, 13.2, 18.6%). To detect HRV change of this magnitude, a hypothetical trial would require a sample size of 660 patients for conventional medications or 1232 patients for all treatment classes. CONCLUSION: Pharmacologic, biobehavioral and exercise strategies for secondary prevention of CAD significantly increase HRV. This review provides a framework to assist efforts to evaluate the contribution of HRV change to CAD prognosis.     

Can negative cardiac effect of proton pump inhibitor and high-dose H2-blocker have clinical influence on patients with stable angina?

BACKGROUND: Aspirin and anti-platelet drugs are used commonly for patients with coronary heart disease. Proton pump inhibitor (PPI) and high-dose H2-blocker were recommended for preventing NSAIDs-related ulcer. Previously H2-blocker reported to have some negative cardiovascular effects. Additionally, a recent in vitro study showed that PPI reduced cardiac contractility. In this study, we evaluated whether chronic administration of PPI and high-dose H2-blocker affects left ventricular function. METHOD: Fifty-two stable angina patients were enrolled and classified into PPI group ([P]; lansoprazole: 15mg/day, n=28), H2-blocker group ([H]; famotidine: 40mg/day, n=8), and control ([C]; none or mucosal-defense drug, n=16). Eligible patients showed normal cardiac function in initial catheterization without administrated PPI or H2-blocker. They received percutaneous coronary intervention and follow-up catheterization. We compared changes in ejection fraction (EF: %), end diastolic/systolic volume index (EDVI/ESVI: ml/m(2)), and peak positive/negative dp/dt (+/-dp/dt: mmHg/s) in left ventricular angiography series. RESULT: There were no significant differences among three groups regarding patient characteristics, backgrounds of angiographic and intervention, except for fewer smokers in [C]. Other drugs such as beta- and Ca-blocker did not have effects on cardiac function except for aspirin during 255+/-115 days follow-up. Rate of EF changes significantly decreased in [P], and tended to decrease in [H] (C: 3.8+/-9.8%, H: -1.6+/-7.6%, P: -2.1+/-5.9%; p<0.05 for [C] vs. [P]). Those of ESVI changes were significantly greater in [P], and tended to be greater in [H] (C: -4.5+/-16.2%, H: 4.9+/-15.5%, P: 7.3+/-16.2%; p<0.05 for [C] vs. [P]), though, EDVI changes' were similar (C: 2.5+/-8.9%, H: 2.6+/-3.6%, P: 1.6+/-6.1%; p=ns). Rate of +/-dp/dt-changes tended to decrease in [H] (+dp/dt: C: 3.9+/-15.5%, H: -10.0+/-25.2%, P: 0.3+/-19.6%; p=ns, -dp/dt: C: -0.1+/-19.5%, H: -8.5+/-20.4%, P: 5.7+/-27.7%; p=ns). CONCLUSION: In this study, PPI and high-dose H2-blocker have EF-reducing tendency. However, these changes were small and these drugs seemed to exhibit little influence clinically.     

Change in Colonic Motility After Extrinsic Autonomic Denervation in Dogs

Changes in colonic motility were compared indogs undergoing autonomic denervation of the paraaorticand presacral (group A), paraaortic (group B), ormesocolonic region (group C), and sham operation (group D). Five bipolar recording electrodes wereplaced into the seromuscular layer of the colon andrectum. The numbers of continuous electrical responseactivity and contractile electrical complex after an intragastric olive oil injection were smallerin group A than in the other groups (P < 0.05) fromthree weeks through six months after denervation. Thisdifference was significant even in the proximal colon. These data suggest that the pelvic plexus mayplay an important role in colonic motility including theproximal colon. The damage to the plexus did not recoverfor at least six months after denevation. Pelvic plexus injury may thus be one ofpossible explanations for the prolonged change in bowelhabit after anterior resection of the rectum.     

Present status and prospects of living-related liver transplantation

Living-related liver transplantation (LRLT) is a relatively new surgical modality that has developed, in part, to overcome the shortage of available cadaveric livers for transplantation and as a method to provide liver graft implants from living donors for patients end-stage with liver disease in areas where the use of cadaveric livers is not yet practiced or permitted. Since 1988 almost 500 LRLTs have been performed globally. The safety of donors who provide a portion of their liver for grafting is of utmost concern, and only one donor death from this procedure has been reported in the literature. Postoperative survival in recipients depends on their pretransplant physical status, but emergency patients in rapid need of a liver have a poorer survival than elective LRLT patients for whom survival is about 80%. Children and infants are the main recipients of LRLTs, but adult patients particularly in Japan, are increasing in number, and present indications for LRLT surgery include not only cholestatic end-stage liver diseases but also metabolic disorders affecting the liver and emergency LRLTs for fulminant hepatic failure. Many ethical problems relating to the concept of liver transplantation, donor liver source, recipient selection, and reimplantation have yet to be resolved. But we believe that LRLTs and cadaveric liver transplantations are saving lives and that the practice should be continued.