Nomogram predictive model for differentiation between renal oncocytoma and chromophobe renal cell carcinoma at multi-phasic CT: a retrospective study.

AIM: To develop a predictive model to discriminate renal oncocytoma (RO) from chromophobe renal carcinoma (chRCC) using multiphase computed tomography (CT). MATERIALS AND METHODS: Two hundred and five cases of renal tumours were analysed retrospectively regarding attenuation values during four CT phases, in addition to age, size, and sex. Then, logistic analysis was applied and a nomogram model developed to predict the most significant variables that can be used to differentiate between both tumour types. The cases were histopathologically proven as 81 cases of RO and 124 cases of chRCC. RESULTS: There was no association between the sex of the patient and the tumour types (p=0.41); however, there was a significant positive association between RO and the age of the patient (odds ratio 1.05; 95% confidence interval 1.02-1.08; p=0.001)) and a significant negative association between tumour size and RO (odds ratio 0.81; 95% confidence interval 73-90; p<0.001). There was a significant difference between tumour types in the contrast-enhanced phases. Logistic regression showed that absolute arterial enhancement (AAE) and absolute venous enhancement (AVE) are the most significant predictors for discriminating between tumour types. Combining these variables, size, AAE, and AVE were the best classifiers to discriminate between tumour types with an area under the curve of 0.90. A nomogram model was developed using these variables to predict RO probability in different case scenarios. CONCLUSION: The nomogram can predict the probability of RO from chRCC by using the best predictors, size, AAE, and AVE, with high accuracy.

Dual effect of selenium loaded chitosan nanoparticles on growth, antioxidant, immune related genes expression, transcriptomics modulation of caspase 1, cytochrome P450 and heat shock protein and Aeromonas hydrophila resistance of Nile Tilapia (Oreochromis niloticus).

Nowadays there is a great attention for nanotechnology in aquaculture production. It has an efficient role in nutrients and drugs delivery, ponds sterilization, water treatment and aquatic diseases reduction. Till now, there is no available data on impact of selenite-loaded chitosan nanoparticles (SeChNPs) on Nile tilapia. Hence, the current study investigated the effects of selenite-loaded chitosan nanoparticles supplementation on the growth, immune, antioxidant and apoptotic related genes as well as resistance to Aeromonas hydrophila of Nile tilapia, Oreochromis niloticus. A total of 400 fish were randomly divided into four groups, and each group retained five replicates. The control group was fed a basal diet (with inorganic se), other groups fed diets supplemented with SeChNPs 0.5, 1 and 2 g/kg diet. The loading concentration of Se to ChNPs was 0.3, 0.6 and 1.2 mg/0.5, 1 and 2 gm respectively. Fish groups fed SeChNPs (0.5 and 1 g/kg) exhibited the highest final body gain, better feed utilization. Additionally, the expression of myostatin gene was down-regulated by 0.2 and 0.3 fold in group fed 0.5 and 1 g/kg SeChNPs when compared with control group. Dietary inclusion of SeChNPs increased serum lysozyme, alternative complement and myeloperoxidase activities and immunoglobulin type M level. Supplementation of SeChNPs at the level of 2 g/kg up-regulated glutathione peroxidase, superoxide dismutase and catalase expression by 1.12, 4.9 and 2.31 folds respectively, in comparison with control group. In contrast, the levels of C- reactive protein and malondialdehyde were reduced. The expression of IL-10, IL-8, TNF-α and IL-1ß genes was up-regulated after dietary inclusion of different levels of SeChNPs in a dose dependent manner. Post-challenge, the highest survival rate was detected in group fed 2 g/kg SeChNPs (93%) in contrast, the control group was displayed the lowest survival rate (45%). After challenge with A. hydrophila, the expression of caspase 1 was up-regulated in groups fed 1 and 2 g/kg of SeChNPs. Moreover, the maximum down-regulation of cytochromes P450 and heat shock protein were found in 2 g/kg SeChNPs supplemented group (reduced by 0.4 and 0.6-fold, respectively, when compared with control group). In conclusion, the ameliorative effects of SeChNPs on Nile tilapia growth resulted from immune stimulatory and free radicals scavenging effects of selenium loaded chitosan nano composite.

Low energy shock wave-delivered intravesical botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder.

PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

Investigation for anticancer activity of the newly synthesized p-Methoxyphenyl maleanilic acid and the diagnostic property of its 99mTc-analogue.

PURPOSE: The limitations of the current chemotherapeutics are the main rational to develop and/or explore new anticancer agents and radiolabeled analogues for cancer early diagnosis. MATERIALS AND METHODS: The newly synthesized p-methoxyphenyl maleanilic acid (MPMA) was prepared, characterized and investigated for its anticancer activity. MPMA screened in-vitro against human hepatocellular carcinoma (HepG-2), human colon carcinoma (HCT-116) and human breast carcinoma (MCF-7) cell lines. Furthermore, the in-vivo screening was performed by radiolabeling of MPMA with technetium-99m (99mTc) and investigating its biological distribution in normal mice and solid tumor models. Moreover, MPMA and its radiolabeled analogue were docked to Y220C and Y220S mutants of p53 (p53Y220C and p53Y220S) in an effort to confirm their affinity to cancer as well as to investigate, virtually, the mechanism of action of MPMA. RESULTS: The results revealed significant potency of MPMA against HepG-2 cell line (IC50 = 56.2 ± 1.5 µg/mL) if compared to HCT-116 (IC50 = 89.9 ± 1.8 µg/mL) and MCF-7 (IC50 = 104 ± 2.7 µg/mL) cell lines. The radiolabeling yield was optimized to be 90.2 ± 2.1%. The radiolabeled MPMA showed a good localization in the site of solid tumor (15.1 ± 1.6%ID/g) at 2 h post intravenous administration to the tumor bearing mice. CONCLUSIONS: Collectively, the findings confirmed the potential anticancer activity of MPMA and the possible use of 99mTc-MPMA for cancer diagnosis and monitoring.

Radiolabeling, biological distribution, docking and ADME studies of 99mTc-Ros as a promising natural tumor tracer.

Rosmarinic acid (Ros) is one of phenolic metabolites with powerful potency as an anticancer agent, with different mechanisms to diminish the cancer cells. This current study represents radiolabeling of Ros with 99mTc using SnCl2 in pH4 for 15 min at 60 °C, The yield up to 92.2%. Biological evaluation in normal and cancer mice revealed the localization of the tracer in tumor tissue. Furthermore, docking and ADME (Absorption, Distribution, Metabolism, and Excretion) studies were performed, The resulted data clarifies the use of Ros as a promissing natural tracer.

Small bowel polyp resection using device-assisted enteroscopy in Peutz-Jeghers Syndrome: Results of a specialised tertiary care centre.

INTRODUCTION: Enteroscopy resection of small bowel polyps in Peutz-Jeghers syndrome has only been described in small case series. Herein, we aimed to assess the efficacy of enteroscopy resection of small bowel polyps within a specialised tertiary care centre and the impact on intraoperative enteroscopy. METHODS: This was an observational single-centre study. All adult Peutz-Jeghers syndrome patients followed in the Predisposition Digestive Ile-de-France network who underwent an endoscopic resection of at least one small bowel polyp ≥ 1 cm by enteroscopy between 2002-2015 were included. Small bowel polyps were detected under a dedicated screening programme by previous capsule endoscopy and/or magnetic resonance enterography, performed every 2-3 years. Complete treatment was defined as the absence of polyps ≥ 1 cm after conventional endoscopic resection. Intraoperative enteroscopy or surgical resection were indicated in incomplete treatments. The overall complete treatment rate including conventional enteroscopy and intraoperative enteroscopy was also considered. RESULTS: Endoscopic resection of 216 small bowel polyps (median: 8.6 per patient, size: 6-60 mm) was performed by 50 enteroscopies in 25 patients (mean age: 36 years, range: 18-71, 56% male) with small bowel polyp ≥ 1 cm. Twenty-three patients (92%) underwent 42 screening capsule endoscopies and 14 (57%) had 23 magnetic resonance enterographies during a median follow-up of 60 months. Complete treatment was achieved in 76%. Intraoperative enteroscopy and surgical resection were performed in four (16%) and two (8%) patients. Intraoperative enteroscopy improved by 16% the complete treatment rate and the overall rate was 92%. The complication rate was 6%. CONCLUSION: This long-term study confirmed the efficacy and safety of endoscopic resection of small bowel polyps in Peutz-Jeghers syndrome. Intraoperative enteroscopy can be a complementary approach in selected cases.

Activation of Nrf2 by ischemic preconditioning and sulforaphane in renal ischemia/reperfusion injury: a comparative experimental study.

Objectives of the study were to investigate impact of ischemic preconditioning (Ipre) and sulforaphane (SFN) and combination of them on nuclear factor 2 erythroid related factor 2 (Nrf2) gene and its dependent genes, heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase1 (NQO-1) and inflammatory cytokines TNF-alpha, IL1beta, and intercellular adhesion molecule-1 (ICAM1) and caspase-3 in renal ischemia/reperfusion (I/R) injury. Ninety male Sprague Dawely rats were classified into 5 groups (each consists of 18 rats): sham, control, Ipre, sulforaphane and Sulfo+Ipre. Each group was subdivided into 3 subgroups each containing 6 rats according to time of harvesting kidney and taking blood samples; 24 h, 48 h, and 7 days subgroups. Renal functions including serum creatinine, BUN were measured at basal conditions and by the end of experiment. Expression of Nrf2, HO-1, NQO-1, TNF-alpha, IL-1beta, and ICAM-1 was measured by real time PCR in kidney tissues by the end of experiment. Also, immunohistochemical localization of caspase-3 and chemical assay of malondialdehyde (MDA), GSH and SOD activity were measured in kidney tissues. Both Ipre and SFN improved kidney functions, enhanced the expression of Nrf2, HO-1, and NQO-1, attenuated the expression of inflammatory (TNF-alpha, IL-1, and ICAM-1) and apoptotic (caspase-3) markers. However, the effect of sulforaphane was more powerful than Ipre. Also, a combination of them caused more improvement in antioxidant genes expression and more attenuation in inflammatory genes but not caspase-3 than each one did separately. Sulforaphane showed more powerful effect in renoprotection against I/R injury than Ipre as well as there might be a synergism between them at the molecular but not at the function level.

Antithrombotic activity of garlic: its inhibition of the synthesis of thromboxane-B2 during infusion of arachidonic acid and collagen in rabbits.

Rabbits were given collagen and arachidonic acid intravenously. Blood pressure, platelet counts, plasma thromboxane-B2 (TXB2) and plasma 6-keto-prostaglandin F1 alpha, (6-keto-PGF1 alpha) were determined. Both thrombogenic agents, upon infusion of a lethal dose, caused thrombocytopenia, indicative of in vivo platelet aggregation and hypotension. These changes were associated with an increase in plasma levels of TXB2 and 6-keto-PGF1 alpha measured by radioimmunoassay (RIA). Pretreatment of rabbits with an aqueous extract of garlic (500 mgkg) provided protection from thrombocytopenia and hypotension. Thromboxane-B2 synthesis was significantly reduced in animals pretreated with garlic and then injected with a lethal dose of either collagen or arachidonic acid. The amount of TXB2 synthesized in these animals was not sufficient to induce thrombocytopenia or hypotension. All animals pretreated with garlic were well protected against the effects of collagen or arachidonate infusion, and no apparent symptoms were observed in these animals. These observations indicate that garlic may be beneficial in the prevention of thrombosis.

Histopathological evidence of protective action of garlic against collagen and arachidonic acid toxicity in rabbits.

Soluble rat tail tendon collagen produced respiratory distress, agitation, convulsions and finally death in rabbits when infused intravenously (i.v.) in lethal doses. Similar observations were noted when a lethal dose of arachidonic acid (unsaturated essential fatty acid) was infused. These agents caused thrombocytopenia, indicative of in vivo platelet aggregation, hypotension and increased levels of thromboxane (TX) B2 (a stable metabolite of TXA2) in the plasma. Histopathological examination of lung, heart and liver tissue indicated that the lungs and livers of treated animals were adversely affected, while heart tissues appeared to be normal. Histopathological examination of lung and liver tissues of animals pretreated with garlic, then treated with a lethal dose of collagen or arachidonic acid showed a significant reduction in the damage observed compared to animals not pretreated with garlic.

Collagen toxicity in rabbits.

Different preparations of soluble collagen, from rabbit skin, rat skin, rat tail tendon and guinea-pig skin, produced respiratory distress, agitation, convulsions and finally death when infused intravenously in lethal doses. Analysis of plasma enzyme levels indicated significant increases in total, cardiac and hepatic lactate dehydrogenase, suggesting that damage to the liver occurred as a result of collagen infusion. Histopathological examination of lungs, livers and hearts of collagen-treated rabbits confirmed that damage had occurred to the lungs and livers of these animals, while heart tissues appeared to be normal. The source of collagen did not appear to influence its toxicity at the tissue level.

Characterization of five chemistries and three particle sizes of stationary phases used in supercritical fluid chromatography.

Sub-2-microns particles employed as supporting phases are known to favor column efficiency. Recently a set of columns based on sub-2-microns particles for use with supercritical fluid mobile phases have been introduced by Waters. Five different stationary phase chemistries are available: BEH silica, BEHEthyl-pyridine, X Select CSH Fluorophenyl, HSS C18 SB and BEH Shield RP18. This paper describes the characterization of 15 stationary phases, the five different chemistries, and three particle sizes, 1.7 (or 1.8), 3.5 and 5 microns, with the same carbon dioxide­methanol mobile phase and a set of more than a hundred compounds. The interactions established in the 15 different chromatographic systems used in supercritical fluid chromatography (SFC) are assessed with linear solvation energy relationships (LSERs).The results show the good complementarity of the five column chemistries, and their comparative location inside a classification map containing today around 70 different commercial phases. Among the five different chemistries, the HSS C18 SB phase displays a rather unusual behavior in regards of classical C18 phases, as it displays significant hydrogen­bonding interactions. Besides, it appears, as expected, that the BEH Ethyl­pyridine phase has weak interactions with basic compounds. The effect of particle size was studied because smaller particles induce increased inlet and internal pressure. For compressible fluids,this pressure change modifies the fluid density, i.e. the apparent void volume and the eluting strength.These changes could modify the retention and the selectivity of compounds in the case of method trans-fer, by using different particle sizes, from 5 down to 1.7 m. A hierarchical cluster analysis shows that stationary phase clusters were based on the phase chemistry rather than on the particle size, meaning that method transfer from 5 to 1.7 microns can be achieved in the subcritical domain i.e. by using a weakly compressible fluid.

The effect of indomethacin and metamizole on ureteral motility and urine flow in sheep.

The objective of this study was to evaluate the effect of two non-steroid anti-inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1-2 mg/kg) and metamizole (60-120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction.