Cycloart-23-ene-3β, 25-diol stimulates GLP-1 (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats: A mechanistic approach

In previous study, we have reported cycloart-23-ene-3β, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3β, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5 mg/kg, p.o.), IV- cycloart-23-ene-3β, 25-diol (1 mg/kg, p.o.). The cycloart-23-ene-3β, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7–36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7–36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3β, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats.     

Anaesthetic and Obstetric challenges of morbid obesity in caesarean deliveries-a study in South-eastern Nigeria

Background

Morbid obesity of parturient has become very important in perinatal medicine because of a worldwide obesity epidemic. Morbid obesity of parturient is reportedly associated with severely increased anaesthetic and obstetric risk.

Objective

To determine the prevalence rate, anaesthetic and obstetric complications in morbidly obese parturient that had caesarean delivery in a Nigerian tertiary care centre.

Methods

The obstetric theatre records and case files were reviewed for caesarean deliveries in the University of Nigeria Teaching Hospital, Enugu, Nigeria from May 2008 to December 2010. A sample size of 250 patients, calculated based on a prevalence rate of 19%, confidence interval of 95% , a power of 80% and a finite population of zero was used to determine the prevalence rate of morbid obesity (Body Mass Index of greater than or equal to 35kg/m²).

Results

There were thirty-one patients with morbid obesity (12.4%). The average Body Mass Index (BMI) was 38.3kg/m²(SD ± 2.99). Other findings included macrosomia (7 or 25.8%), gestational diabetes (13%) and pregnancy induced hypertension (7 or 22.5%).There were two neonatal deaths but no maternal deaths.

Conclusion

The prevalence rate of morbid obesity is about 10% in Nigerian women of child bearing age. This mirrors a World Health Organisation report published in the World Health Organisation Global Information Base.     

Variation of Papp-A Level in the First Trimester of Pregnancy and Its Clinical Outcome

Introduction

Abnormalities in maternal serum marker levels and fetal measurements obtained during the first trimester screening can be a marker not only for certain chromosomal disorders and anomalies in the fetus but also for specific pregnancy complications. In particular, low maternal serum pregnancy-associated plasma protein-A (PAPP-A), at 11–13 weeks of gestation, is associated with stillbirth, infant death, intrauterine growth restriction, preterm birth, and pre-eclampsia in chromosomally normal fetuses, while a raised nuchal translucency is associated with specific structural abnormalities and genetic syndromes. We have studied the serum Papp-A level in 560 pregnant patients (11–13 weeks gestation) registered at Bharati Hospital and Research Centre, Pune. All patients undergoing testing were followed till the delivery and their neonatal outcome was also taken into consideration.

Aims and Objectives

Our aim is to study the pregnancy outcome in relation to the variations of Papp-A level in the first trimester of pregnancy.

Materials and Methods

Every patient visiting the antenatal OPD was counseled for testing of First Trimester Screening to assess fetal well-being. Patients who were registered for delivery at our hospital were taken into the trial. Blood samples were taken at 11–13 weeks of pregnancy and sent to the PerkinElmer lab for analysis. Results were expressed in Multiple of Median and patients having MOM value less than 0.5 were carefully observed till the delivery, and a thorough neonatal examination was done by a pediatrician.

Observations

524 patients were included in the trial out of which 452 patients were found to have a normal Papp-A level of >0.5 MOM. All these patients were followed further during the antenatal period where 18 patients developed preterm labor and few patients developed pregnancy-induced hypertension. The obstetric outcome of patients with a normal Papp-A level was fairly uneventful as compared to others with a low Papp-A level.

Conclusions

Though Papp-A level in the first trimester of pregnancy (11–13 weeks) is an important predictor of future obstetric outcome, it has poor positive predictive value. Patients having a Papp-A level less than 0.5 MOM have a high risk for preterm delivery, fetal growth restriction, and stillbirths along with increased incidence of hypertensive disorders of pregnancy. A low Papp-A level is a useful indicator of risk of preterm delivery and future chance of development of pregnancy-induced hypertension.     

Chk2*1100delC Acts in synergy with the Ron receptor tyrosine kinase to accelerate mammary tumorigenesis in mice

The CHEK2 (Chk2 in mice) polymorphic variant, CHEK2*1100delC, leads to genomic instability and is associated with an increased risk for breast cancer. The Ron receptor tyrosine kinase is overexpressed in a large fraction of human breast cancers. Here, we asked whether the low penetrance Chk2*1100delC allele alters the tumorigenic efficacy of Ron in the development of mammary tumors in a mouse model. Our data demonstrate that Ron overexpression on a Chk2*1100delC background accelerates the development of mammary tumors, and shows that pathways mediated by a tyrosine kinase receptor and a regulator of the cell cycle can act to hasten tumorigenesis in vivo.     

Techniques and efficacy of flexible endoscopic therapy of Zenker’s diverticulum

Zenker’s diverticulum(ZD) is an abnormal hypopharyngeal pouch often presenting with dysphagia. Treatment is often sought with invasive surgical management of the diverticulum being the only mode of definitive therapy.Primarily done by an open transcervical approach in the past, nowadays treatment is usually provided by otolaryngologists using a less invasive trans-oral technique with a rigid endoscope. When first described, this method grew into acceptance quickly due to its similar efficacy and vastly improved safety profile compared to the open transcervical approach. However, the main limitation with this approach is that it may not be suitable for all patients. Nonetheless, progress in the field of natural orifice endoscopic surgery over the last 10-20 years has led to the increase in utilization of the flexible endoscope in the treatment of ZD. Primarily performed by interventional gastroenterologists, this approach overcomes the prior limitation of its surgical counterpart and allows adequate visualization of the diverticulum independent of the patient’s body habitus. Additionally, it may be performed without the use of general anesthesia and in an outpatient setting, thus further increasing the utility of this modality, especially in elderly patients with other comorbidities. Today, results in more than 600 patients have been described in various published case series using different techniques and devices demonstrating a high percentage of clinical symptom resolution with low rates of adverse events. In this article, we present our experience with flexible endoscopic therapy of Zenker’s diverticulum and highlight the endoscopic technique, outcomes and adverse events related to this minimally invasive modality.     

Feasibility and safety of endoscopic cryoablation at the duodenal papilla: Porcine model

AIM: To assess the feasibility and safety of liquid nitrogen spray cryoablation at the duodenal papilla in a porcine model.METHODS: This prospective study protocol was approved by the University of Florida Institutional Animal Care and Use Committee. Six pigs underwent liquid nitrogen spray cryotherapy at the duodenal papilla. Freeze time of 20-s was applied per cycle (4 cycles/session). Survival animals (n = 4) were monitored for adverse events. Hemoglobin, white blood count, liver tests, and lipase were obtained at baseline and post-treatment. EGD was performed on day#7 to evaluate the papilla and for histology. All animals were euthanized and necropsy was performed at the end of the one-week survival period. Feasibility was defined as successful placement of the decompression tube in the duodenum, followed by delivery of spray cryotherapy to the duodenal papilla. Safety was determined by monitoring post-treatment blood tests and clinical course. Treatment effect was defined as endoscopic and histologic changes after cryotherapy. This was established by comparing endoscopic and histologic findings from mucosal biopsies prior to cryotherapy and on post-operative day (POD)#7. Full-thickness specimen was obtained post-mortem to assess depth of injury.RESULTS: Spray cryotherapy was feasible and successfully performed in all 6/6 (100%) animals. Cryospray with liquid nitrogen (four 20-s freeze-thaw cycles) at the duodenal papilla resulted in white frost formation at and around the target region. The mean procedural time was 54.5 min (range 50-58 min). All six animals studied had stable blood pressure, heart rate, and pulse oximetry measurements during the procedure. There were no significant intra-procedural adverse events. There were no significant differences in hemoglobin, white cell count, liver tests or lipase from baseline to post-cryotherapy. Survival animals were monitored daily post-operatively without any clinical ill effects from the cryotherapy. There was no bleeding, infection, or perforation on necropsy. Endoscopic on POD#7 showed edema and ulceration at the duodenal papilla. On histology, there was loss of crypt architecture with moderate to severe necrosis and acute mixed inflammatory infiltration in each specimen following cryotherapy. The extent of cryogen-induced tissue necrosis (depth of injury) was limited to the mucosa on full-thickness specimen evaluation.CONCLUSION: Endoscopic liquid nitrogen spray cryotherapy is feasible and safe for ablation at the duodenal papilla in a porcine model.     

When a cure becomes the pathology: mechanical bowel obstruction due to herbal pharmacobezoar. A case report with review of literature

Bezoars are intra-luminal concretions of ingested material which accumulate within the bowel. They are termed pharmacobezoars when the constituent material is drugs. We report a 64-year-old female with abdominal pain and obstipation for 3 days. Patient had completed anti-tuberculous combination therapy for suspected abdominal tuberculosis 25 years ago. She exhibited features of shock with a right iliac fossa lump. Abdominal X-ray displayed multiple air-fluid levels with densely cluttered radio-opacities in the right lower quadrant. Laparotomy revealed a palpable mid-ileal intra-luminal lump, adherent to the ascending colon and proximal ileum necessitating resection. Ex vivo examination of resected specimen revealed numerous tablets aggregating proximal to an ileal stricture. The patient post-operatively confirmed the tablets resembled the herbal laxatives she had been consuming. Pharmacobezoars can lead to subacute intestinal obstruction. Numerous drugs have been implicated. Patients with partial gastrectomy and vagotomy are at risk. CT is the pre-eminent diagnostic modality. The treatment options for pharmacobezoars include lavage, endoscopic retrieval, in addition to surgery. Pharmacobezoars need a high index of suspicion for pre-operative diagnosis. A detailed history and correlation with radioimaging can offer important cues. One can prevent pharmacobezoars by abstaining from unwarranted medications and identifying those at risk.