Evaluation of Cissus quadrangularis extracts as an inhibitor of COX, 5-LOX, and proinflammatory mediators

Ethnopharmacological relevance

Cissus quadrangularis is an ancient medicinal plant. It is an active ingredient of one Ayurvedic formula called “Laksha Gogglu”. Its stem is used in food preparation in India. Traditionally it is used to treat various diseases like asthma, indigestion, ear diseases, irregular menstruation, skin diseases, piles, fractured bones, etc.

Aim of the study

This study aimed to evaluate the ability of the plant extracts to inhibit cycloxygenase (COX-1), cycloxygenase (COX-2), and 5-lipoxygenase (5-LOX) enzyme activity. Western blot analysis was also carried out in the quest to determine the effect of active acetone fraction of Cissus quadrangularis (AFCQ) on proinflammatory mediators as acetone extract is found to be the most effective in this study.

Materials and methods

The differential extract of the stem were tested for enzyme inhibition of COX and 5-LOX using spectroscopic and polarigraphic method. Effective acetone extract was partially purified by silica column, one of the active fraction showed dual inhibition against COX and 5-LOX. Western blotting shows downregulation of proinflammatory mediators as well as upregulation of phase-II enzymes.

Results

AFCQ extract showed COX and 5-LOX inhibition with IC₅₀ values of 7 μg/ml, 0.4 μg/ml, and 20 μg/ml for COX-1, COX-2 and 5-LOX respectively. It also showed anti-inflammatory activity on RAW 264.7 cell line with IC₅₀ value 65 μg/ml. In addition to this it is showing inhibition of proinflammatory mediators like iNOS and TNFα, along with translocation of Nrf-2 and upregulation of HO-1.

Conclusion

AFCQ is a COX and 5-LOX inhibitor isolated from the stems of Cissus quadrangularis. It is also effectively downregulate the iNOS, TNFα, and upregulation of HO-1.     

Pancreatic sphincterotomy： Technique, indications, and complications

Pancreatic sphincterotomy serves as the cornerstone of endoscopic therapy of the pancreas. Historically, its indications have been less well-defined than those of endoscopic biliary sphincterotomy, yet it plays a definite and useful role in diseases such as chronic pancreatitis and pancreatic-type sphincter of Oddi dysfunction. In the appropriate setting, it may be used as a single therapeutic maneuver, or in conjunction with other endoscopic techniques such as pancreatic stone extraction or stent placement. The current standard of practice utilizes two different methods of performing pancreatic sphincterotomy： a pull-type sphincterotome technique without prior stent placement, and a needleknife sphincterotome technique over an existing stent. The complications associated with pancreatic sphincterotomy are many, although acute pancreatitis appears to be the most common and the most serious of the early complications. As such, it continues to be reserved for those endoscopists who perform a relatively high-volume of therapeutic pancreaticobiliary endoscopic retrograde chola ngio-pancreatography.     

Zygomycosis--a case report and overview of the disease in India

A case of zygomycosis caused by Rhizopus oryzae in a diabetic patient previously misdiagnosed as invasive pulmonary aspergillosis and an overview of the disease in India are presented. The case was diagnosed by direct microscopy, histopathologic examination and culture. Following surgical resection of pulmonary cavity under cover of amphotericin B administration, the patient recovered completely. Of 461 cases reported to-date, approximately 70% had been diagnosed at the Postgraduate Institute of Medical Education and Research, Chandigarh, in north India. This may be attributed to better awareness, expertise and infrastructural facilities for mycological diagnosis than to any particular regional preponderance of the disease. Rhino-orbito-cerebral manifestations were the most common feature of zygomycosis (269 cases), followed by cutaneous disease (66 cases), which is in conformity with the pattern prevalent worldwide. The etiologic agents encountered were Rhizopus oryzae, Apophysomyces elegans, Saksenaea vasiformis, Cunninghamella bertholletiae, Absidia corymbifera, Basidiobolus ranarum and Conidiobolus coronatus. In contrast to cases from the developed world where transplant recipients and patients with haematological malignancies seem to be most vulnerable to zygomycosis, the most common risk factor in India was uncontrolled diabetes mellitus. Amphotericin B was the mainstay of various treatment modalities employed. The relevance of a strong clinical suspicion and early diagnosis of zygomycosis for favourable prognosis can hardly be over-emphasised.     

Biliary drainage by using stents without a central lumen: a pilot study

BACKGROUND: Despite several attempts to make the conventional tubular stents with a central lumen for flow less susceptible to a biofilm buildup and thereby prevent clogging, this goal has remained elusive. We hypothesized that the creation of pathways for fluid flow around the stent instead of through it would avoid this problem. The aim of our study was to report the development and the evaluation of a novel lumen-less stent. METHODS: By using a software computer modeling, a 10F "winged" stent was designed. A pilot feasibility study was performed by using a prototype of this stent for endoscopic biliary drainage in 5 patients with malignant biliary obstruction. OBSERVATIONS: Modeling data revealed that the winged stent offers a larger surface area for flow, higher velocity of flow, and increased flow rates compared with the conventional tubular stent. In the clinical trial, there was a significant decrease of serum bilirubin after the placement of this stent (serum bilirubin before and 2 weeks after stent placement, 14.94 +/- 5.7 mg/dL vs. 2.86 +/- 1.4 [p < 0.004]), accompanied by radiologic evidence of decompression of the biliary system. CONCLUSIONS: We have shown that it is possible to provide adequate biliary drainage by using a stent without a lumen. Such a design may have potential clinical advantages over existing designs.     

Congenital spinal lipomas — Tumor versus hamartoma

Congenital spinal lipomas as a form of dysraphism are frequently reported in literature. A few studies have highlighted their histologic features and found them different from lipomas in other parts of the body. In a review of eight cases of spinal lipomas, we found heterotopic tissue in seven. Neural tissue, muscle, bone and cartilage were frequently encountered. The presence of meningothelial cells in one case was an unusual finding. These findings support the concept of their hamartomatous origin. Malignancy, occurring later in life in one of the heterotopic elements is known, though uncommon, and is one of the reasons, besides neurologic deficit, for long term follow-up.     

Endoscopic cryotherapy: experimental results and first clinical use

BACKGROUND: Cryotherapy or the application of extreme cold has many potential applications in gastroenterology including tissue destruction and hemostasis but until now its development has been prevented by the lack of a delivery device suitable for use through the endoscope. We report here our experience with prototype devices using both liquid nitrogen driven by a cryosurgical system and cryogenic refrigerants (nitrous oxide and carbon dioxide) at or near ambient temperature. METHODS: Cryotherapy was applied to the distal esophageal mucosa of dogs via a flexible catheter passed through an upper endoscope. In other dogs, cryotherapy was used for hemostasis in a bleeding ulcer model. The procedure was also used for palliation in a 58-year-old man with unresectable adenocarcinoma of the stomach with pyloric channel obstruction. RESULTS: Freezing of the superficial mucosa was nearly instantaneous. All dogs survived the procedure and appeared to thrive. Histologic evaluation revealed significant necrosis of the superficial epithelial layer accompanied by a fibrinocellular infiltrate on the surface. These markers of acute injury subside by the fourth to sixth day and are replaced by regenerating epithelium, a process that is virtually complete by day 10. In the hemostasis experiments, bleeding ceased immediately after cryospraying of the lesions but resumed on thawing in most cases. Application of cryotherapy in the patient resulted in reduction of the pyloric mass with no immediately apparent adverse effects. CONCLUSIONS: These data, although preliminary, demonstrate the feasibility of endoscopic cryotherapy using a simple hand-held device. This device has broad potential for use in gastroenterology including ablation of superficial epithelium, debulking of large tumors and hemostasis.     

Pain: the overlooked symptom in gastroparesis

OBJECTIVE: Abdominal pain has not been reported generally as a significant feature of the clinical presentation of patients with gastroparesis. METHODS: Using a standardized questionnaire, we analyzed the clinical features of 28 consecutive patients referred with established or suspected gastroparesis over a 4-yr period. The diagnosis of gastroparesis was supported by abnormalities in gastric emptying studies (GES), electrogastrography (EGG), or upper endoscopy (EGD). Diagnostic tests were reviewed. RESULTS: A total of 12 male (mean age 39.5 yr) and 18 female patients (mean age 39.6 yr) were included in this study. These patients had been symptomatic for an average of 37.8 months before their referral to our center. Seven of these patients had insulin-dependent diabetes. Idiopathic gastroparesis was present in more than half of the patients. The symptom profile of the 28 patients was as follows: nausea, 92.9%; abdominal pain, 89.3%; early satiety, 85.7%; and vomiting, 67.9%. The pain was described as burning, vague, or crampy in nature. Only 36% localized to the upper abdomen. In all, 60% of patients complained of postprandial pain, whereas 80% complained of nocturnal pain that interfered with their normal sleeping pattern. In general, pain responded poorly or not at all to prokinetic agents. CONCLUSIONS: Nausea and abdominal pain are the most common complaints of patients with gastroparesis. In 80% of patients, GES and EGG correlated positively.     

DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease

Molecular markers of pancreatic neoplasia could aid in the evaluation of visible pancreatic lesions and indicate neoplasia invisible to imaging. We evaluated methylation-specific PCR (MSP) assays that detect aberrantly methylated DNA for their use as markers of pancreatic neoplasia. Methylation analysis was done on pancreatic juice collected endoscopically or surgically from 155 individuals with suspected pancreatic disease: 56 patients had pancreatic ductal adenocarcinoma, 17 had intraductal papillary mucinous neoplasms, 26 had symptomatic chronic pancreatitis, 12 controls lacked evidence of pancreatic disease, and 44 were asymptomatic individuals at increased risk of developing familial pancreatic cancer undergoing screening for pancreatic neoplasia. Pancreatic juice DNA was analyzed for promoter methylation using conventional MSP assays for 17 genes. For six genes, pancreatic juice methylation was quantified using real-time quantitative MSP (QMSP; Cyclin D2, FOXE1, NPTX2, ppENK, p16, and TFPI2). Quantifying pancreatic juice methylation using QMSP with a cutoff of >1% methylated DNA could better predict pancreatic cancer than detecting methylation using conventional MSP. In the endoscopic group, 9 of 11 patients with pancreatic cancer, but none of 64 individuals without neoplasia had > or =1% methylation for two or more of the best five QMSP assays (82% sensitivity and 100% specificity; P < 0.0001). The prevalence of pancreatic juice methylation in patients with chronic pancreatitis was less than in patients with pancreatic cancer but higher than in controls and similar to high-risk individuals. The detection and quantification of aberrantly methylated DNA in pancreatic juice is a promising approach to the diagnosis of pancreatic cancer.     

Accuracy and reliability of the endoscopic classification of portal hypertensive gastropathy

BACKGROUND: There is no consensus regarding the endoscopic classification of the severity of portal hypertensive gastropathy. This study compared the accuracy and reproducibility of the 2-category classification system (2-CCS) with the 3-category classification system (3-CCS). METHODS: Ninety-eight endoscopic pictures of portal hypertensive gastropathy and 22 of nonspecific gastritis were selected. Eight duplicate sets were generated, each in a different random order. These were shown to 6 experienced endoscopists during 2 sessions 1 week apart with 4 slide sets at each session. Each picture was scored by using either the 2-CCS or 3-CCS. Kappa statistics and percent agreement were used to estimate the reproducibility and agreement. RESULTS: The mean percentage agreement among the 4 separate readings for each observer was significantly lower for the 3-CCS compared with the 2-CCS (mean [standard deviation] = 33.5% [8.9%] vs. 64.9% [9.1%]; p = 0.0001). The mean (SD) interobserver kappa values were 0.44 (0.03) for the 3-CCS and 0.52 (0.04) for the 2-CCS (p = 0.02), and the respective intraobserver kappa values were 0.43 (0.1) and 0.63 (0.06) (p = 0.002). CONCLUSIONS: Even though both the 2-CCS and 3-CCS have substantial limitations with regard to specificity and reliability, there were better agreement and reproducibility with the simpler classification system for portal hypertensive gastropathy.