The Niemann-Pick C1 like 1 (NPC1L1) inhibitor ezetimibe improves metabolic disease via decreased liver X receptor (LXR) activity in liver of obese male mice.

Dyslipidemic patients with diabetes mellitus, including metabolic syndrome, are at increased risk of coronary heart disease. It has been reported that ezetimibe, a cholesterol absorption inhibitor, improves metabolic diseases in mice and humans. However, the underlying mechanism has been unclear. Here we explored the effects of ezetimibe on lipid and glucose homeostasis. Male KK-A(y) mice were fed a high-fat diet, which is the mouse model of metabolic syndrome, with or without ezetimibe for 14 weeks. Ezetimibe improved dyslipidemia, steatosis, and insulin resistance. Ezetimibe decreased hepatic oxysterols, which are endogenous agonists of liver X receptor (LXR), to decrease hepatic lipogenic gene expressions, especially in stearoyl-CoA desaturase-1 (SCD1), leading to a remarkable reduction of hepatic oleate content that would contribute to the improvement of steatosis by reducing triglycerides and cholesterol esters. Simultaneously, hepatic ß-oxidation, NADPH oxidase and cytochrome P450 2E1 (CYP2E1) were reduced, and thus reactive oxygen species (ROS) and inflammatory cytokines were also decreased. Consistent with these changes, ezetimibe diminished c-Jun N-terminal kinase (JNK) phosphorylation and improved insulin signaling in the liver. In vitro study using primary hepatocytes obtained from male SD rats, treated with oleate and LXR agonist, showed excess lipid accumulation, increased oxidative stress and impaired insulin signaling. Therefore, in obese subjects, ezetimibe reduces hepatic LXR activity by reducing hepatic oxysterols to lower hepatic oleate content. This improves steatosis and reduces oxidative stress, and this reduction improves insulin signaling in the liver. These results provide insight into pathogenesis and strategies for treatment of the metabolic syndrome.

Bile acid binding resin improves metabolic control through the induction of energy expenditure.

BACKGROUND: Besides well-established roles of bile acids (BA) in dietary lipid absorption and cholesterol homeostasis, it has recently become clear that BA is also a biological signaling molecule. We have shown that strategies aimed at activating TGR5 by increasing the BA pool size with BA administration may constitute a significant therapeutic advance to combat the metabolic syndrome and suggest that such strategies are worth testing in a clinical setting. Bile acid binding resin (BABR) is known not only to reduce serum cholesterol levels but also to improve glucose tolerance and insulin resistance in animal models and humans. However, the mechanisms by which BABR affects glucose homeostasis have not been established. We investigated how BABR affects glycemic control in diet-induced obesity models. METHODS AND FINDINGS: We evaluated the metabolic effect of BABR by administrating colestimide to animal models for the metabolic syndrome. Administration of BABR increased energy expenditure, translating into significant weight reduction and insulin sensitization. The metabolic effects of BABR coincide with activation of cholesterol and BA synthesis in liver and thermogenesis in brown adipose tissue. Interestingly, these effects of BABR occur despite normal food intake and triglyceride absorption. Administration of BABR and BA had similar effects on BA composition and thermogenesis, suggesting that they both are mediated via TGR5 activation. CONCLUSION: Our data hence suggest that BABR could be useful for the management of the impaired glucose tolerance of the metabolic syndrome, since they not only lower cholesterol levels, but also reduce obesity and improve insulin resistance.

Novel hybrid mesh surgery combines sacrocolpopexy with transvaginal mesh placement for pelvic organ prolapse.

Mesh surgeries, such as sacrocolpopexy and transvaginal mesh surgery, are commonly used to treat pelvic organ prolapse. Although mesh surgeries have a high success rate, they are unsuitable for some patients. For a patient with pelvic organ prolapse and highly calcified multiple fibroids, we performed hybrid sacrocolpopexy combined with transvaginal mesh surgery with a method modified for the patient's condition. Three months after surgery, the results were highly satisfactory. This approach is simple, secure, and versatile for patients who are not good candidates for conventional mesh surgeries. This novel hybrid mesh surgery is an option for treating various types of pelvic organ prolapse.

Evaluation of laparoendoscopic single-site gynecologic surgery with a multitrocar access system.

OBJECTS: Laparoendoscopic single-site surgery (LESS) is an ideal approach for gynecologic surgery and yields better cosmetic results. However, a standard umbilical approach with LESS is not appropriate for gynecologic surgery requiring intra-abdominal suturing and dissection requiring traction. Therefore, we have developed a new multitrocar access system for gynecologic LESS. The purpose of this study was to evaluate the efficacy of gynecologic LESS using this access system. METHODS: This access system consists of one 12-mm trocar, two 5-mm trocars, and a 5-mm flexible laparoscope. Two 5-mm trocars with small port heads were inserted cross-wise on opposite sides of the sleeve of the centrally positioned 12-mm trocar to maintain triangulation. Thirty-eight patients with various gynecologic conditions underwent LESS with this access system. The results of these surgeries were retrospectively compared to those of conventional laparoscopic procedures. RESULTS: Of the 38 LESS procedures performed with this access system, none was up-converted, converted to an open laparotomy, or required blood transfusion. The Salpingo-oophorectomy with LESS had several benefits, such as no extension of the skin incision of the trocar site and no leakage of the contents of the ovarian cyst into the peritoneal cavity, over that with conventional laparoscopy. A comparison of LESS (11 patients) and conventional laparoscopy (16 patients) for total hysterectomy showed no significant difference in total blood loss (234.0 mL vs. 221.6 mL) or the weight of the resected uterus (276.0 g vs. 285.0 g), although the mean total operative time was greater with LESS (199.0 min vs. 168.5 min). CONCLUSION: Our multitrocar access system is safe and secure, and can be adapted for various gynecologic surgeries involving complicated procedures. LESS with this access system achieves results comparable to those of conventional laparoscopy with 4 ports, although the operative time is longer.

Maternal risk factors for small-for-gestational age newborns in Japanese dichorionic twins.

AIM: To investigate the maternal risk factors for small-for-gestational age (SGA) newborns in Japanese dichorionic (DC) twins. METHODS: A retrospective study was conducted from 2003 to 2008 on 340 DC twin pregnancies resulting in two live births. Newborns were classified as SGA if their birth weight was below the 10th percentile according to Japanese singleton norms. Statistical differences were evaluated between pregnancies resulting in appropriate-for-gestational age (AGA) pairs and those resulting in at least one SGA neonate. RESULTS: The study population consisted of AGA/AGA (50.8%), AGA/SGA (37.0%) and SGA/SGA pairs (12.0%). Logistic regression analysis identified significant interrelations for SGA with maternal nulliparity (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.30-0.91), smoking (OR 3.25, 95% CI 1.09-9.66), assisted reproductive technology (OR 0.52, 95% CI 0.30-0.89), pregnancy-induced hypertension (OR 2.00, 95% CI 1.01-4.31), pregravid weight (kg) (unitary OR 0.94, 95% CI 0.91-0.97) and monthly weight gain (kg/month) (unitary OR 0.25, 95% CI 0.14-0.44). Bivariable receiver operating characteristic curves were generated for monthly weight gain (area under the curve [AUC] 0.626, cutoff 1.41 kg/month, P<0.001) and total weight gain (AUC 0.615, cutoff 14.0 kg, P<0.001). CONCLUSION: Cigarette smoking and weight gain control are relatively modifiable factors for which interventional management is necessary to avoid perinatal problems arising from SGA pregnancy. Further studies are needed to investigate optimal nutrition, health guidance and subsequent weight gain control that lead to concrete improvement in maternal and infant prognoses.

The influence of assisted reproductive technology on women with pregnancy-induced hypertension: a retrospective study at a Japanese Regional Perinatal Center.

OBJECTIVE: To evaluate clinical features of assisted reproductive technology (ART) patients with pregnancy-induced hypertension (PIH) compared to spontaneously conceived PIH patients. METHODS: We retrospectively compared PIH incidence, maternal outcomes, and neonatal outcomes among these patients. RESULTS: Preeclampsia, cesarean rate, and massive maternal bleeding were significantly more common in the ART group. Neonatal outcomes showed no significant difference between the groups. Multiple regression analysis revealed ART as an independent risk factor for preeclampsia. However, higher cesarean rate and massive bleeding were mainly associated with multiple pregnancy. CONCLUSION: ART patients with PIH had an increased incidence of preeclampsia, cesarean delivery, and massive maternal hemorrhage.

Fetal heart rate patterns in monochorionic twins following acute twin-twin transfusion.

Background. We present here 2 cases of acute twin-twin transfusion occurred during vaginal labor in monochorionic-diamniotic twin pregnancies. Case. Fetal heart rate tracings showed tachycardia in the donor twin in the first case, while they showed reassuring patterns in both twins in the second case. Conclusion. These differences in changes of fetal heart rate in the donor twins following acute twin-twin transfusion may be resulted from the differences in amount of transfusion and elapsed time.