Involvement of heparanase in the pathogenesis of acute kidney injury: Nephroprotective effect of PG545

Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor. I/R induced tubular damage and elevation in serum creatinine and blood urea nitrogen to a higher extent in heparanase over-expressing transgenic mice vs. wild type mice. Moreover, TGF-\u3b2, vimentin, fibronectin and \u3b1-smooth muscle actin, biomarkers of fibrosis, and TNF\u3b1, IL6 and endothelin-1, biomarkers of inflammation, were upregulated in I/R induced AKI, primarily in heparanase transgenic mice, suggesting an adverse role of heparanase in the pathogenesis of AKI. Remarkably, pretreatment of mice with PG545 abolished kidney dysfunction and the up-regulation of heparanase, pro-inflammatory (i.e., IL-6) and pro-fibrotic (i.e., TGF-\u3b2) genes induced by I/R. The present study provides new insights into the involvement of heparanase in the pathogenesis of ischemic AKI.Our results demonstrate that heparanase plays a deleterious role in the development of renal injury and kidney dysfunction,attesting heparanase inhibition as a promising therapeutic approach for AKI

Removal of a partially covered stent by endoscopic substent dissection

Herein we describe a new technical endoscopic removal of embedded partially covered esophageal stent that was inserted to treat a iatrogenic perforation of esophagus. Usually, partially covered stents can be removed by the stent-in-stent technique. In this case, the embedded stent could not be removed safely with this technique; so we performed a sub stent dissection to detach the stent from the esophageal wall

Endoscopist-directed balanced propofol sedation is safe and effective in patients undergoing outpatient colonoscopy

Background and Aims: Propofol administered in combination with other moderate sedation medications (balanced propofol sedation [BPS]) is an appealing and effective sedation regimen for gastrointestinal (GI) endoscopy procedures. However, product labeling dictates propofol be administered only by anesthesiology personnel. We evaluated the safety of endoscopist-directed as well as anesthesiologist-administered BPS during outpatient colonoscopy. Methods: We performed a retrospective cohort study using prospectively collected endoscopy data where endoscopist-directed BPS is standard practice. Measured patient outcomes included: BPS drug dosages, postcolonoscopy oxygen saturation levels, pulse, and systolic/diastolic blood pressures, need for mask bag ventilation or endotracheal intubation, aborted colonoscopy due to sedation, hospital admission postcolonoscopy, and mortality. Results: From April 1 to November 30, 2013, 1036 patients undergoing outpatient colonoscopy (mean age 56.4 years, 55% males, 32% American Society of Anesthesiologists [ASA] I, 59% ASA II, 9% ASA III) received endoscopist-directed BPS. During the same time period, 40 patients (mean age 66.6 years, 55% males, 33% ASA II, 67% ASA III) received anesthesiologist-administered BPS. Indications for colonoscopy for the endoscopist-directed BPS included 352 (34%) colorectal cancer screening/surveillance, 404 (39%) evaluation of lower GI symptoms, 156 (15%) positive fecal occult blood, and 124 (12%) inflammatory bowel disease. BPS dosages (mean ± standard deviation) per patient were Fentanyl 0.05 mg (fixed dose), midazolam 1.6 mg ± 0.5 mg (range: 1-5 mg), and propofol 104 mg ± 62 mg (range: 10-460 mg). Propofol doses correlated inversely with patient age (r = −0.35; P < 0.001), and the mean Propofol dose was lower as ASA score increased: ASA I - 115 mg, ASA II - 103 mg, and ASA III - 75 mg (P < 0.01). No patient required bag mask ventilation, endotracheal intubation, or hospital admission. There were no aborted colonoscopies secondary to sedation and no mortality. All patients were discharged directly to home. Conclusions: Endoscopist-directed BPS appears safe and effective for low-, intermediate- and high-risk patients undergoing outpatient colonoscopy

Accuracy and Quality Assessment of EUS-FNA: A Single-Center Large Cohort of Biopsies

Introduction. Thorough quality control (QC) study with systemic monitoring and evaluation is crucial to optimizing the effectiveness of EUS-FNA. Methods. Retrospective analysis was composed of investigating consecutive patient files that underwent EUS-FNA. QC specifically focused on diagnostic accuracy, impacts on preexisting diagnoses, and case management. Results. 268 patient files were evaluated. EUS-FNA cytology helped establish accurate diagnoses in 92.54% (248/268) of patients. Sensitivity, specificity, PPV, NPV, and accuracy were 83%, 100%, 100%, 91.6%, and 94%, respectively. The most common biopsy site was the pancreas (68%). The most accurate location for EUS-FNA was the esophagus, 13/13 (100%), followed by the pancreas (89.6%). EUS-FNA was least informative for abdominal lymph nodes (70.5%). After FNA and followup, eight false negatives for tumors were found (3%), while 7.5% of samples still lacked a definitive diagnosis. Discussion. QC suggests that the diagnostic accuracy of EUS-FNA might be improved further by (1) taking more FNA passes from suspected lesions, (2) optimizing needle selection (3) having an experienced echo-endoscopist available during the learning curve, and (4) having a cytologist present during the procedure. QC also identified remediable reporting errors. In conclusion, QC study is valuable in identifying weaknesses and thereby augmenting the effectiveness of EUS-FNA

Anti-Inflammatory, Antimicrobial, and Vasoconstriction Activities of an Anti-Hemorrhoidal Mixture of <i>Alchemilla vulgaris</i>, <i>Conyza bonariensis</i>, and <i>Nigella sativa</i>: In Vitro and Clinical Evaluations

Nigella sativa, Conyza bonariensis, and Alchemilla vulgaris are highly recommended in Greco-Arab traditional medicine as anti-hemorrhoid medicinal plants. The efficacy and safety of a topical cream (HPC) consisting of water–ethanol extracts of these three plants were evaluated here in vitro and in a randomized, double-blind, placebo-controlled study (RDBPC). HPC showed no significant cytotoxic effects in fibroblast cell line 3T3 (LDH-release and MTT assay); it inhibited the nitric oxide production by cultured monocyte cell line THP-1 in a dose-dependent manner (reaching the control levels of untreated cells at a concentration of 100 μg/mL). HPC showed a dose-dependent antibacterial activity against Escherichia coli (60% inhibition compared to Ampicillin at 5 mg/disc) and a significant vasoconstriction effect on intestinal vein rings (40% increase compared to phenylephrine). In a RDBPC with 77 hemorrhoidal disease (patients ages 19–61 years with a median grade of hemorrhoids of 2.0), we determined the anti-hemorrhoid efficacy and safety of HPC. The patients were randomly assigned to the HPC group (54 patients) or the placebo group (23 patients). They were asked to apply 2–3 mL of HPC or placebo twice daily for 6 days. The degree of hemorrhoidal disease severity, hemorrhage severity, pain, and itching served as an evaluation of the HPC efficacy. Compared to the placebo group, the obtained results showed that 6 days of treatment with HPC reduced the indexes of hemorrhage severity, severity of pain, and severity of itching to 0–1, 1, and 1 after 6 days, respectively. In conclusion, patients treated with HPC had a significant clinical improvement in all disease severity parameters compared to placebo. In vitro evaluations proved HPC to have significant antimicrobial, anti-inflammatory, and vasoconstriction effects. Therefore, HPC represents an interesting alternative treatment for hemorrhoidal disease