Involvement of gap junctions in the increased contraction of bovine oviducts at pre-ovulation observed in vitro.

In brief: Spontaneous contraction of oviductal smooth muscle is essential for gamete transport to the fertilization site in mammals. This study sheds light on the mechanism of elevated contraction amplitude in the bovine oviductal isthmus just before ovulation. Abstract: Rhythmic contraction of the oviducts is essential for transporting gametes and embryos at peri-ovulation; however, its regulatory mechanism during the estrous cycle is unclear. Meanwhile, it is reported that ion currents regulate muscle contraction. Our study aimed to clarify the involvement of ion channels and gap junctions in regulating oviductal motility during the estrous cycle in cattle. The isthmic sections of bovine oviducts collected just after ovulation (0-4 days after ovulation), at the mid-late luteal stage (10-17 days), and at the follicular stage (1-3 days before ovulation) were used in the experiments. The frequency and amplitude of contraction of the oviductal strips in the longitudinal direction were examined using the Magnus system. The frequency was not different among the estrous stages. Conversely, the amplitude was significantly higher at the follicular stage. The blockers of voltage-dependent calcium channels, both IP3 receptor and ryanodine receptors, chloride channel, and gap junction reduced the amplitude. Additionally, mRNA and protein expression of GJA1, a component of the gap junction, in the smooth muscle tissues of the oviductal isthmus were significantly higher in the follicular stage. In addition, estradiol-17ß (E2; 1.0 ng/mL) significantly increased GJA1 mRNA expression in cultured smooth muscle tissues after 24 h and GJA1 protein expression in cultured smooth muscle cells after 48 h. These results suggest that local levels of E2 in the oviductal isthmus ipsilateral to an ovary with a dominant follicle support the increased contraction amplitude of bovine ipsilateral oviducts by elevating the gap junction expression.

Immunohistochemical identification of epithelial cell types in the isthmus of bovine oviduct: Comparison with the ampulla.

The oviductal epithelium consists of ciliated and non-ciliated cells, and their numbers vary depending on the segment of the oviduct and stage of the estrous cycle. Compared with the ampulla, fewer cyclic changes in the number of the two types of cells occur in the isthmus. Recently, we have reported that the epithelium in the ampullary oviduct is composed of many types of cells during different translational/transcriptional states, and their numbers change during the estrous cycle. However, detailed information regarding the epithelial cell subtypes lining the isthmic oviductal epithelium has not yet been reported. In this study, we aimed to identify the epithelial subtypes in the isthmus of the oviduct using immunohistochemistry. Some similarities and differences were observed between the ampulla and isthmus. As observed in the ampulla, epithelial cells of the isthmus expressed either FOXJ1 (ciliogenesis marker) or PAX8 (non-ciliated cell marker). The estrous cycle affected the number of Ki67+ cells but not that of ciliated cells. A relatively high rate of Ki67+ cells (60%) was observed at 1-4 days after the ovulation. Interestingly, unlike the ampulla, Ki67+/FOXJ1+ cells (12.6 ± 1.1%) were discovered in the isthmus. Double staining for Ki67 with FOXJ1, PAX8, or Centrin-1 (a centriole marker) revealed that Centrin-1 was localized on the apical surface of some Ki67+/FOXJ1+ cells. In conclusion, some epithelial cell subtypes exist in the isthmus of the oviduct and isthmus-specific cell subtypes have been identified. These region-specific cells may provide functional and morphological differences between the ampulla and isthmus of the oviduct.

A Chinese Medicine, Tokishakuyakusan, Increases Bovine Oviductal Tonus via G Protein-Coupled Estrogen Receptor 1.

Early embryo and sperm transport through the oviductal isthmus depends on the contraction and relaxation of the smooth muscle layers. Dysfunction of the oviduct transport is considered to be one of the causes of infertility. For human infertility, Chinese medicine is used in East Asia. Although there are many clinical reports regarding Tokishakuyakusan (TSS), there is little scientific evidence that it affects infertility. In this study, we investigated the effect of TSS on bovine oviductal contraction and relaxation via the G protein-coupled estrogen receptor 1 (GPER1). We collected bovine oviductal isthmic tissues at four stages of the estrous cycle, classified based on a macroscopic observation of the ovary. The Magnus method was used to monitor longitudinal contractility (frequency, contraction force, and tonus). The effects of TSS solution, GPER1 agonist (G-1), and antagonist (G-15) on oviductal contractility were examined. The protein expression level of GPER1 in the oviductal isthmic smooth muscle of each estrous stage was assessed by Western blotting. Although TSS did not affect frequency and contraction force, the tonus was significantly increased by TSS or G-1 at all stages (p < 0.05), and the effect was especially highest at days 1-4 after ovulation. The addition of G-15 significantly suppressed the TSS-induced increase of oviductal tonus at all stages (p < 0.05). There was no significant difference in GPER1 protein expression among the estrous stages. TSS affects oviductal contractility by increasing tonus via GPER1, and it may accelerate gamete and early embryo transport by contracting the oviducts longitudinally.

[Measuring end-of-life care efficacy and related factors in the staff members of elderly care facilities].

Based on Bandura's social learning theory, this study conceptualized the end-of-life care efficacy (EoLCE) of elderly care facility staff. In Analysis 1, an EoLCE scale was developed. Factor analysis identified two factors ­instrumental care efficacy and emotional care efficacy­ with psychometric adequacy. In Analysis 2, a path analysis was used to examine the relationships between EoLCE and the number of care experiences provided (Care Experiences) as well as the four theory-based sources of self-efficacy: the frequency of feeling a sense of achievement (Achievement), number of opportunities to observe role models, number of opportunities to receive linguistic persuasions (Linguistic Persuasions), and negative emotional responses to end-of-life care. After controlling for these sources, we found that Care Experiences negatively influenced emotional care efficacy. Achievement had the strongest significant relationship with EoLCE. The three other sources showed significant relationships with EoLCE, but there was no relationship between instrumental care efficacy and Linguistic Persuasions. To increase EoLCE, the subjective number of social learning experiences relevant to end-of-life care was important, rather than the number of care experiences provided.

[Ascending-descending Aortic Bypass and Aortic Valve Replacement for Aortic Coarctation with Bicuspid Aortic Valve and an Aberrant Right Subclavian Artery;Report of a Case].

A 53-year-old woman was developed congestive heart failure. She was diagnosed as having aortic coarctation, incompetent bicuspid aortic valve and an aberrant right subclavian artery by using echocardiography and enhanced computed tomography. Ankle brachial pressure index(ABI)in the right was 0.71 and 0.69 in the left. Blood pressure of the right arm was 60 mmHg lower than that of the left arm. To avoid perioperative adverse cardiac events due to a 2-staged operation, we performed ascending-descending aortic bypass and aortic valve replacement simultaneously through a median sternotomy. The heart was retracted cranially, and a vascular prosthesis was anastomosed to the descending aorta just above the diaphragm in an end-to-side manner. Then the graft was placed curvilinearly around the right atrium and was anastomosed to the ascending aorta. After the operation, the right and left ABI increased to 0.90 and 0.98 respectively. There was no pressure difference between the arms. The postoperative course was uneventful.

Identification of Coronary Artery Orifice to Prevent Coronary Complications in Bioprosthetic and Transcatheter Aortic Valve Replacement.

BACKGROUND: The aim of this study was to identify anatomical variations in coronary artery orifices among high-risk patients with a small aortic root undergoing bioprosthetic aortic valve replacement (BAVR) and transcatheter aortic valve replacement (TAVR) in order to prevent coronary orifice obstruction perioperatively. METHODS AND RESULTS: Coronary orifice and root structure were identified in 400 patients using aortic multidetector-row computed tomography (MDCT). We measured the aortic root diameter; intercommissural distances; and distance from coronary orifice to valve annulus, commissure, and sinotubular junction. We examined positional relationships between the coronary orifice and stent post, or sewing cuff of the bioprosthetic valve and leaflet of the transcatheter aortic valve. Most left coronary artery orifices were distributed near the center of the non-left and left-right commissures; right ones were relatively distributed on the non-right commissural side. Thirty-four patients (8.5%) with BAVR (coronary orifice near the commissure: 31, 7.8%; low takeoff: 5, 1.3%; and both: 2) and 39 (9.8%) with TAVR were at risk for coronary orifice obstruction. During BAVR, one-stitch rotation of the stent and one-stitch rotation with intra-annular implantation were used in near-commissure and low takeoff cases, respectively. During TAVR, percutaneous coronary intervention may be required in the height of the coronary orifice was ≤10 mm from the base of the ventricle aortic junction. CONCLUSIONS: Potential coronary complications during BAVR and TAVR in high-risk patients for coronary obstruction were identified using preoperative aortic MDCT. Choice of appropriate surgical technique or valve is essential.

Genistein inhibits glucocorticoid amplification in adipose tissue by suppression of 11ß-hydroxysteroid dehydrogenase type 1.

Excess glucocorticoids promote visceral obesity, hyperlipidemia, and insulin resistance. The main regulator of intracellular glucocorticoid levels is 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive glucocorticoids into bioactive forms such as cortisol in humans and corticosterone in rodents. Hexose-6-phosphate dehydrogenase (H6PD), which is colocalized with 11ß-HSD1 in the intralumen of the endoplasmic reticulum, supplies a crucial coenzyme, NADPH, for full reductase activity of 11ß-HSD1. Therefore, it is possible that inhibition of 11ß-HSD1 will become a considerable medical treatment for metabolic diseases including obesity and diabetes. Genistein, a soy isoflavone, has received attention for its therapeutic potential for obesity, diabetes, and cardiovascular disease, and has been proposed as a promising compound for the treatment of metabolic disorders. However, the mechanisms underlying the pleiotropic anti-obesity effects of genistein have not been fully clarified. Here, we demonstrate that genistein was able to inhibit 11ß-HSD1 and H6PD activities within 10 or 20min, in dose- and time-dependent manners. Inhibition of 11ß-HSD2 activity was not observed in rat kidney microsomes. The inhibition was not reversed by two estrogen receptor antagonists, tamoxifen and ICI182,780. A kinetic study revealed that genistein acted as a non-competitive inhibitor of 11ß-HSD1, and its apparent Km value for 11-dehydrocorticosterone was 0.5µM. Genistein also acted as a non-competitive inhibitor of H6PD, and its apparent Km values for G6P and NADP were 0.9 and 3.3µM, respectively. These results suggest that genistein may exert its inhibitory effect by interacting with these enzymes.

Management of ostium secundum atrial septal defect in the era of percutaneous trans-catheter device closure: 7-Year experience at a single institution.

OBJECTIVES: This study aimed to review the single institutional experience of the repair of secundum atrial septal defect (ASD) after the initiation of percutaneous trans-catheter device closure, to confirm the current management strategy and outcomes. METHODS: From August 2005 to December 2012, a total of 1026 (659 females, age 27±21 years) consecutive patients underwent the repair of ASD. Including eight patients who converted to surgical repair, 317 patients (31%) underwent surgical repair and 709 (69%) underwent trans-catheter device closure. RESULTS: An embolized device into the left atrium was surgically retrieved in one patient soon after trans-catheter device closure without any postoperative complications. The other patient developed left atrium to aorta fistula due to late erosion, and required the removal of implanted device and patch closure of fistula and ASD 3 months after trans-catheter device closure. Whereas serious central nerve system complications occurred in three patients after the surgical repair including a 75-year-old patient with postoperative transient atrial fibrillation who subsequently developed aspiration pneumonia and died; there were no mortalities and no morbidities associated with cranial nerve function after trans-catheter device closure. A number of patients approached through partial sternotomy with limited skin incision have increased per year, and the length of skin incision was 5.1±1.2cm in pediatric patients weighing less than 15kg (n=40), 6.9±1.9cm in the remaining pediatric patients (n=91), and 10.0±2.5cm in young adult females (n=10). CONCLUSION: Percutaneous trans-catheter ASD closure was safely performed under the support of a surgical team. The cosmetic outcome of surgical closure is improving after initiation of partial sternotomy via limited skin incision for the pediatric population and young adult females. Prior to the treatment, the physicians must thoroughly inform patients and families of the advantages and disadvantages of both treatment options.

Resveratrol inhibits 11ß-hydroxysteroid dehydrogenase type 1 activity in rat adipose microsomes.

It has been suggested that resveratrol, a polyphenol in wine, can regulate adiposity because it decreases adipose deposition in mice and rats; however, the mechanism underlying this effect has not been fully clarified. In humans and rodents, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is expressed in liver and adipose tissue. 11ß-HSD1 converts inactive glucocorticoid into active glucocorticoid in adipocytes. Activated glucocorticoid plays an important role in the pathogenesis of central obesity. The objective of this study was to investigate the effects of resveratrol on 11ß-HSD1 activity in rodent adipose tissue. 11ß-HSD1 activity in microsomes from rat mesenteric adipose depots and 3T3-L1 adipocytes was determined in the presence of 11-dehydrocorticosterone with or without varying concentrations of resveratrol. Significant inhibition of 11ß-HSD1 by resveratrol was observed in rat adipose microsomes and 3T3-L1 adipocytes within 10 min. Time- and dose-dependent effects were also observed. The 11ß-HSD1 activity by resveratrol was also inhibited in rat epididymal adipose tissue, and this inhibition was not recovered by estrogen receptor blockers. The kinetic study revealed that resveratrol acted as a non-competitive inhibitor of 11ß-HSD1. Ki and IC50 values of resveratrol were 39.6 and 35.2 µM respectively. Further, resveratrol did not affect the activities of 11ß-HSD2 and hexose-6-phosphate dehydrogenase. These results suggest that the most likely mechanism of 11ß-HSD1 inhibition by resveratrol is via interaction between resveratrol and 11ß-HSD1 enzyme, rather than via a transcriptional pathway. We demonstrated that the antiobesity effects of resveratrol may partially be attributed to the inhibition of 11ß-HSD1 activity in adipocytes.

[A case of postoperative convulsive seizure following tranexamic acid infusion during aortic valve replacement].

We present a case of postoperative convulsive seizure in an 84-year-old man who underwent an aortic valve replacement. The patient had hypertension associated with hyperaldosteronism and chronic interstitial nephritis. The duration of cardiopulmonary bypass was 74 min. A generalized seizure lasting approximately 1 minute occurred at 1 hour after the patient's arrival in the intensive care unit. A total of 9 generalized seizures, which were aborted by the intravenous administration of diazepam (5 mg), occurred every 30 min. For seizure control, the continuous administration of midazolam (2 mg x hr(-1)) was initiated. On the day after the discontinuation of the midazolam, a generalized seizure recurred and an infusion of sodium thiopental was started. No further seizures were observed. On the sixth postoperative day, the patient was extubated and discharged without any neurological abnormalities. Imaging showed old small areas of cerebral infarction in the basal ganglia, which were not thought to have contributed to the seizures. The blood sugar, sodium, and calcium levels were within the normal limits. The seizures were likely due to a total dose of 8 g of tranexamic acid (TXA) administered intraoperatively. Possible mechanisms of TXA-induced seizures include blockage of inhibitory cortical y -aminobutyric acid-A receptors.

Mitral valve plasty in an adult patient without a right superior vena cava.

Persistent left superior vena cava without a right superior vena cava is an extremely rare condition. We report the case of a 65-year-old woman with this condition who underwent mitral valve plasty. During cardiac catheterization, the asymptomatic patient with mitral valve prolapse syndrome was found to have a persistent left superior vena cava without a right superior vena cava. During mitral valve plasty, cardiopulmonary bypass was established using bicaval drainage through the persistent left superior vena cava and the right atrium. A cannula was inserted into the persistent left superior vena cava to provide a large surgical field in the left atrium. We selected a technique that involved direct insertion of an L-shaped cannula into the persistent left superior vena cava and obtained a clear view of the surgical field. Proper assessment of the right superior vena cava is necessary when a persistent left superior vena cava is suspected.

Usefulness of an enhanced recovery after surgery protocol for perioperative management following open repair of an abdominal aortic aneurysm.

PURPOSE: To achieve early recovery and early discharge from the hospital by applying an enhanced recovery after surgery (ERAS) protocol, which is mainly used with colonic surgery, for the perioperative management of open AAA surgery. METHOD: One hundred twenty-seven open AAA surgery cases successfully carried out between 2003 and 2011 were included in this study. The ERAS protocol was used for the cases from April 2008 onward, and we performed a comparison of the conventionally treated cases with ERAS cases regarding the start of postoperative oral consumption, the postoperative hospital stay, and hospitalization medical costs. RESULTS: The time to restarting oral consumption and the postoperative hospital stay were significantly shorter for the ERAS group (n = 52) compared to the conventionally managed group (n = 75); with values of 59 ± 15 and 93 ± 25 h (p = 0.021), 9 ± 3 and 16 ± 5 days (p = 0.001), respectively. The medical costs for the ERAS group were 92 % of the costs of the conventionally managed group. CONCLUSION: Use of the ERAS protocol for the perioperative management of open AAA surgery shortened the time before recommencing oral consumption, the postoperative hospital stay, and reduced the medical costs compared to the conventional approach.

17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes.

17Beta-estradiol (E(2)) serves as an anti-obesity steroid; however, the mechanism underlying this effect has not been fully clarified. The effect of E(2) on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis and anabolic lipid metabolism. The key to the intracellular activation of glucocorticoid in adipocytes is 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the production of active glucocorticoids (cortisol in humans and corticosterone in rodents) from inactive 11-keto steroids (cortisone in humans and 11-dehydrocorticosterone in rodents). Using differentiated 3T3-L1 adipocytes, we showed that E(2) inhibited 11beta-HSD1 activity. Estrogen receptor (ER) antagonists, ICI-182 780 and tamoxifen, failed to reverse this inhibition. A significant inhibitory effect of E(2) on 11beta-HSD1 activity was observed within 5-10 min. Furthermore, acetylation or alpha-epimerization of 17-hydroxy group of E(2) attenuated the inhibitory effect on 11beta-HSD1. These results indicate that the inhibition of 11beta-HSD1 by E(2) depends on neither an ER-dependent route, transcriptional pathway nor non-specific fashion. Hexose-6-phosphate dehydrogenase, which provides the cofactor NADPH for full activation of 11beta-HSD1, was unaffected by E(2). A kinetic study revealed that E(2) acted as a non-competitive inhibitor of 11beta-HSD1. The inhibitory effect of E(2) on 11beta-HSD1 was reproduced in adipocytes isolated from rat mesenteric fat depots. This is the first demonstration that E(2) inhibits 11beta-HSD1, thereby providing a novel insight into the anti-obesity mechanism of estrogen.