Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

Low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years

BACKGROUND & AIMS: The colectomy rate in ulcerative colitis (UC) is related to morbidity and to treatment decisions made during disease course. The aims of this study were to determine the colectomy risk in UC in the first decade after diagnosis and to identify factors that may influence the choice of surgical treatment. METHODS: In 1991-1993, 781 UC patients from 9 centers located in 7 countries in northern and southern Europe and in Israel were included in a prospective inception cohort study. After 10 years of follow-up, 617 patients had complete medical records, 73 had died, and 91 had been lost to follow-up. RESULTS: There were no significant differences in age, sex, or disease extent at diagnosis between patients followed for 10 years and those lost to follow-up. The 10-year cumulative risk of colectomy was 8.7%: 10.4% in the northern and 3.9% in the southern European centers (P < .001). Colectomy was more likely in extensive colitis than in proctitis, with an adjusted hazard ratio (HR) of 4.1 (95% CI: 2.0-8.4). Compared with the southern centers, the adjusted HR was 2.7 (95% CI: 1.3-5.6) for The Netherlands and Norway together and 8.2 (95% CI: 3.6-18.6) for Denmark. Age at diagnosis, sex, and smoking status at diagnosis had no statistically significant influence on colectomy rates. CONCLUSIONS: The colectomy rate was found to be lower than that in previous publications, but there was a difference between northern and southern Europe. Colectomy was associated with extensive colitis, but the geographic variations could not be explained.     

Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model

The role of helminth treatment in autoimmune diseases is growing constantly. Systemic lupus erythematosus (SLE) is a multi‐system autoimmune disease with challenging treatment options. Tuftsin–phosphorylcholine (TPC) is a novel helminth‐based compound that modulates the host immune network. This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first‐line therapy for SLE: corticosteroids (methylprednisolone). Lupus‐prone NZBxW/F₁mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5 mg/body weight) or phosphate‐buffered saline (PBS) (control) three times per week once glomerulonephritis, defined as proteinuria of grade > 100 mg/dl, was established. Levels of anti‐dsDNA autoantibodies were evaluated by enzyme‐linked immunosorbent assay (ELISA), splenic cytokines were measured in vitro and the kidney microscopy was analysed following staining. TPC and MP treatments improved lupus nephritis significantly and prolonged survival in NZBxW/F₁ mice. TPC‐treated mice showed a significantly decreased level of proteinuria (P < 0·001) and anti‐dsDNA antibodies (P < 0·001) compared to PBS‐treated mice. Moreover, TPC and MP inhibited the production of the proinflammatory cytokines interferon IFN‐γ, interleukin IL‐1β and IL‐6 (P < 0·001) and enhanced expression of the anti‐inflammatory cytokine IL‐10 (P < 0·001). Finally, microscopy analysis of the kidneys demonstrated that TPC‐treated mice maintained normal structure equally to MP‐treated mice. These data indicate that the small molecule named TPC hinders lupus development in genetically lupus‐prone mice equally to methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.     

Impaired oxidative status as a potential predictor in clinical manifestations of herpes zoster

Oxidative stress, caused by an imbalance between reactive oxygen species and antioxidants, is related to many dermatologic diseases. Increased reactive oxygen species is also associated with various decreased T‐cell immune responses. The incidence and severity of herpes zoster (HZ), which is caused by the reactivation of varicella ‐ zoster virus, increase with age because of declining cell‐mediated immunity. The main purpose of this study was to assess the levels of oxidative stress biomarkers in patients with HZ compared with control subjects. In this case‐control study, the serum levels of total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index, glutathione, superoxide dismutase, and total polyphenol content (TPC) in 43 patients with HZ and 47 age‐matched controls were determined, and their biomarker patterns were compared. TAC and TPC levels were significantly lower in patients with HZ; however, TOS and oxidative stress index levels were significantly higher in comparison with the control (P < .001). In addition, a signi?cantly strong negative correlation was found between TAC and TPC with TOS levels in patients with HZ (r = ?.79, P < .001; r = ?.81, P < .001, respectively). Our findings showed an oxidative stress imbalance in HZ. Whether this change correlates with HZ pathogenesis or is a consequence of the inflammatory response to HZ needs more investigation.     

Free radical scavenging activity from leaves of Acacia nilotica (L.) Wild. ex Delile,an Indian medicinal tree

The present study compares the two extraction methods and evaluates the free radical scavenging activity of Acacia nilotica. Results indicated that the sequential extraction method was effective in concentrating the active principles in the ethanol extract as compared to the maceration method in DPPH assay. Based on the results, free radical scavenging property of the extracts obtained from sequential extraction method was analyzed in different assays to find out the possible antioxidant mechanism. Our results indicate that ethanol extract rich in phenolic and flavonoid contents had potent antioxidant activity and were significant in comparison with all the positive controls used in this study. The possible antioxidant mechanism of the ethanol extract can be due to its hydrogen or electron donating and direct free radical scavenging properties. Hence, the ethanol extract represents a source of potential antioxidants that could be used in pharmaceutical and food preparations.     

Strawberry consumption alleviates doxorubicin-induced toxicity by suppressing oxidative stress

Doxorubicin (Dox), one of the most used chemotherapeutic agents, is known to generate oxidative stress and block DNA synthesis, which result in severe dose-limiting toxicity. A strategy to protect against Dox toxic effects could be to use dietary antioxidants of which fruits and vegetable are a rich source. In this context, strawberry consumption is associated with the maintenance of good health and the prevention of several diseases, thanks to the antioxidant capacities of its bioactive compounds. The aim of the present study was to evaluate the protective effects of strawberry consumption against oxidative stress induced by Dox in rats. Animals were fed with strawberry enriched diet (15% of the total calories) for two months and Dox (10 mg/kg; i.p.) was injected at the end of the experimental period. Strawberry consumption significantly inhibited ROS production and oxidative damage biomarkers accumulation in plasma and liver tissue and alleviated histopathological changes in rat livers treated with Dox. The reduction of antioxidant enzyme activities was significantly mitigated after strawberry consumption. In addition, strawberry enriched diet ameliorated liver mitochondrial antioxidant levels and functionality. In conclusion, strawberry intake protects against Dox-induced toxicity, at plasma, liver and mitochondrial levels thanks to its high contents of bioactive compounds.     

Complications after proctocolectomy and ileal pouch-anal anastomosis in pediatric patients: A systematic review

Background/purposeColectomy with ileal pouch-anal anastomosis (IPAA) is the standard of care for patients with familial adenomatous polyposis (FAP) and refractory ulcerative colitis (UC). The rates of postoperative complications are not well established in children. The objective of this systematic review is to establish benchmark data for morbidity after pediatric IPAA.MethodsPubMed, Embase, and The Cochrane Library were searched for studies of colectomy with IPAA in patients ≤ 21 years old. UC studies were limited to the anti-tumor necrosis factor-α agents era (1998–present). All postoperative complications were extracted.ResultsThirteen studies met the inclusion criteria (763 patients). Compared to patients with FAP, UC patients had a higher prevalence of pouch loss (10.6% vs. 1.5%). Other major complications such as anastomotic leak, abscess, and fistula were uncommon (mean prevalence 4.9%, 4.2%, and 5.0%, respectively, for patients with UC; 8.7%, 4.2%, and 4.3% for FAP). The most frequent complication was pouchitis (36.4% of UC patients).ConclusionsDevastating complications from colectomy and IPAA are rare, but patients with UC have poorer outcomes than those with FAP. Much of the morbidity may therefore stem from patient or disease factors. Multicenter, prospective studies are needed to identify modifiable risks in patients with UC undergoing IPAA.Level of evidencePrognostic, level II.     

Prunus armeniaca L (apricot) protects rat testes from detrimental effects of low-dose x-rays

Exposure to low x-ray doses damages the spermatozoa, mainly by late-onset (ie, after 3 months) oxidative stress. Antioxidants ameliorate oxidation and prevent tissue damage. Prunus armeniaca L (apricot), rich in carotenoids and vitamins, is a potent natural antioxidant. We hypothesized that an apricot-rich diet might ameliorate the detrimental effects of low-dose x-rays on testis tissue. A 20% apricot diet was composed isoenergetically to the regular rodent diet. The total phenolic content, reducing power, and antioxidant capacity of both diets were determined. Sprague-Dawley rats received apricot-rich diets before and after x-ray exposure. Regular diets were given to controls. Rats were exposed to 0.2 Gy x-rays at the eighth week and were euthanized at the 20th postexposure week. Testicular oxidative status was determined by tissue thiobarbituric acid-reactive substances, reduced glutathione, superoxide dismutase, and catalase activities. For histologic evaluation, qualitative and quantitative microscopic determinations were performed, and Leydig and Sertoli cell counts and Johnsen scores were measured. The control diet group had significant testicular oxidative stress and mild tissue deterioration. Leydig and Sertoli cell counts, tubule diameters, and Johnsen scores were significantly decreased in the exposure groups. Apricot-rich diet significantly ameliorated the oxidative status and prevented the damage in tubular histology. The protective effects were prominent when the diet was maintained throughout the time course and were partially protected when the diet was initiated after exposure. The natural antioxidant activity of apricot ameliorates the delayed detrimental effects of low-dose irradiation on testis tissue. The high total antioxidant capacity of the apricot deserves further investigation.     

Gastroprotective mechanism of Bauhinia thonningii Schum

Ethnopharmacological relevance

Bauhinia thonningii Schum. (Cesalpiniaceae) is locally known as Tambarib and used to treat various diseases including gastric ulcer.

Aim of the study

The current study aims to evaluate the gastroprotecive mechanism(s) of methanolic (MEBT) and chloroform (CEBT) extracts of Bauhinia thonningii leaves on ethanol-induced gastric ulceration.

Materials and methods

Gastric acidity, quantification and histochemistry of mucus, gross and microscopic examination, nitric oxide, lipid peroxidation, 2D gel electrophoresis, mass spectroscopy and biochemical tests were utilized to assess the mechanism(s) underlying the gastroprotective effects of MEBT and CEBT. Effect of these extracts into lipopolysaccharide/interferon-γ stimulated rodent cells were done in vitro. In vitro and in vivo toxicity studies were also conducted. Antioxidant activities of MEBT and CEBT were examined using DPPH, FRAP and ORAC assays. Phytochemical analyses of MEBT and CEBT were conducted using chemical and spectroscopic methods.

Results

Gross and histological features confirmed the anti-ulcerogenic properties of Bauhinia thonningii. Gastroprotective mechanism of MEBT was observed to be mediated through the modulation of PAS-reactive substances, MDA and proteomics biomarkers (creatine kinase, malate dehydrogenase, ATP synthase, actin and thioredoxin). MEBT and CEBT showed no significant in vitro and in vivo effects on nitric oxide. Methanolic extract (MEBT) showed superior gastroprotective effects, polyphenolic content and antioxidant activities compared to CEBT. The plant extracts showed no in vitro or in vivo toxicity.

Conclusion

It could be concluded that MEBT possesses anti-ulcer activity, which could be attributed to the inhibition of ethanol-induced oxidative damage and the intervention in proteomic pathways but not the nitric oxide pathway.