Stem cells derived exosomes as biological nano carriers for VCR sulfate for treating breast cancer stem cells.

Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.

Prognostic value of MTSS1 gene expression on acute leukemia patients outcome.

Background: This study aimed to evaluate the prognostic value of the MTSS1 gene expression in patients with acute leukemia. Patients & methods: MTSS1 gene expression was quantified in 120 newly diagnosed acute leukemia patients, by quantitative reverse transcription PCR at diagnosis and after induction chemotherapy therapy. Results: Baseline MTSS1 gene expression was significantly higher in acute leukemia patients compared to the control group (p < 0.001). Acute leukemia patients with low baseline MTSS1 gene expression at diagnosis have significantly shorter overall survival and disease-free survival compared with those with higher expression (p < 0.001 for both). Conclusion: Downregulation of MTSS1 gene expression at diagnosis was associated with poor outcome in either cytogenetic acute myeloid leukemia or B-cell acute lymphoblastic leukemia.

Molecular detection of pathogenic bacteria in the colonic biopsies from patients with Ulcerative Colitis.

Background/Aim: Ulcerative Colitis (UC) is an inflammatory bowel disease which is common in many areas of the world including Egypt. A lot of controversy regarding the pathogenesis of UC exist. The current study is an attempt to detect some pathogenic bacteria in UC patients. Materials and methods: Endoscopic colonic biopsies obtained from 40 patients with ulcerative colitis and 20 controls were analyzed by means of real-time PCR technique for the presence of Clostridium difficile, Helicobacter Pylori (H. pylori) and pathogenic Escherichia Coli (E. coli) which are positive for KPC and/or OXA-48. Results: All patients and control samples were negative for Clostridium difficile. Three of the 40 patient samples (7.5%) and none of the 20 controls were positive for H. pylori with no significant difference between the two groups. KPC-positive E. coli were detected in 11 of the 40 patients (27.5%) and in none of the controls with a significant difference between the two groups (P=0.01). All patients and control samples were negative for OXA-48 positive E. coli. Conclusion: Although this study does not support the claim that Clostridium difficile and/or H. pylori have a role in UC, it greatly suggests that pathogenic E. coli may be involved in one way or another in the course of UC.

Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2−negative (p < 0.001), estrogen receptor−positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Epithelial-Mesenchymal Transition Markers in HCVAssociated Hepatocellular Carcinoma: A Multivariate Follow Up Study.

OBJECTIVE: Validated markers to predict recurrence after surgical resection of hepatocellular carcinoma (HCC) are needed. Little data is available regarding epithelial-mesenchymal transition (EMT) markers in HCC. The objective of this study was to investigate the expression of EMT markers and their correlation with clinicopathological variables and survival in hepatitis C virus (HCV)-associated HCC. METHODS: This longitudinal study included 109 cases of HCV-associated HCC treated with surgical resection. Nine different EMT markers (vimentin, E-cadherin, N-cadherin, Stat3, Snail1, Slug, Twist1, Zeb1 and integrin α5) were evaluated on liver tissue from HCC cases. Twenty fresh HCC samples from the studied cases were used for gene expression of EMT markers by quantitative real time polymerase chain reaction (PCR). RESULTS: EMT markers expression was 71%, 25%, 26%, 27%, 9%, 4%, 72%, 47%, 87% for vimentin, E-cadherin, N-cadherin, Stat3 snail1, slug, twist1, Zeb1 and integrin α5 respectively.  EMT mRNA in HCC tissues correlated with protein expression by 50-70%.  Vimentin was independent predictor of large tumor size (P=0.001), high risk of recurrence (HRR) (P=0.006) and shorter disease free survival (P=0.03) in multivariate analysis.  Reduced E-cadherin was a predictor of HRR (P=0.002). CONCLUSION: Vimentin and E-cadherin were the most powerful prognostic EMT markers in HCV-associated HCC in prediction of recurrence.

Does steroid-free immunosuppression improve the outcome in kidney transplant recipients compared to conventional protocols?

Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation. Steroids are key component of induction protocols, maintenance therapy and in the treatment of various forms of rejection. Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells. Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives. This situation changed with the intro-duction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile. As a result, the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice. This review aims to evaluate the safety and efficacy of various steroid-minimization approaches (steroid avoidance, early steroid withdrawal, and late steroid withdrawal) in kidney transplant recipients. A meticulous electronic search was conducted through the available data resources like SCOPUS, MEDLINE, and Liverpool University library e-resources. Relevant articles obtained through our search were included. A total number of 90 articles were eligible to be included in this review [34 randomised controlled trials (RCT) and 56 articles of other research modalities]. All articles were evaluating the safety and efficacy of various steroid-free approaches in comparison to maintenance steroids. We will cover only the RCT articles in this review. If used in right clinical context, steroid-free protocols proved to be comparable to steroid-based maintenance therapy. The appropriate approach should be tailored individually according to each recipient immuno-logical challenges and clinical condition.

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. METHODS: Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. RESULTS: The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p= 0.41) in AR- and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N- patients (p = 0.03) with median TILs of 20% versus 50% in N+ versus N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05-34.21; p = 0.04). CONCLUSIONS: AR expression was evident in older age (≥50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

The Potential Protective Effect of Orange Peel and Selenium against 17ß-Estradiol- Induced Chronic Non-Bacterial Prostatitis in Rats.

BACKGROUND: Prostate Cancer (PCa) is defined as a major health problem faced by the male population. AIM: We aimed to investigate the protective effects of Orange Peel Extract (OPE) and/or Selenium (Se) on chronic non-bacterial prostatitis in a rat model. METHODS: Fifty-six adult male Wistar albino rats were castrated; after 5 days, they were divided randomly into eight groups (n= 7). The control group received saline treatment; while 17ß-estradiol (E2) (0.25mg/kg) was injected subcutaneously in rats from Groups V, VI, VII, and VIII to induce chronic non-bacterial prostatitis. They were then treated with OPE (400mg/kg body weight; Groups II, IV, VI, and VIII) and/or sodium selenite (0.5mg/kg body weight; Groups III, IV, VII, and VIII) for 30 days. Interleukin-2 (IL2) and Prostate Cancer Antigen 3 (PCA3) mRNA expressions were determined using qPCR; Prostate-Specific Antigen (PSA) protein expression was determined immunohistochemically. Prostate tissue histology was examined by hematoxylin and eosin staining, and the levels of oxidative stress markers and antioxidant enzymes were measured. RESULTS: E2 administration significantly increased IL2 and PCA3 mRNA expressions, and PSA protein expression. It also increased the prostate wet weight and body weight, and lipid peroxidation, nitric oxide, TNF-α, and IL-1ß levels, decreased the glutathione and antioxidant enzyme levels and caused distinct histological alterations in the prostate gland. OPE and/or Se markedly improved all the studied parameters due to their antioxidant properties and anti-inflammatory effects. CONCLUSION: OPE and Se showed protective effects against 17ß-estradiol-induced chronic non-bacterial prostatitis. These results suggest that protection of chronic non-bacterial prostatitis by OPE+Se combination involves anti-oxidation and anti-inflammation. Moreover, their synergistic mechanism was mostly achieved via the regulation of oxidative stress and inflammation processes.

Tissue Profile of CDK4 and STAT3 as Possible Innovative Therapeutic Targets in Urinary Bladder Cancer.

Bladder cancer represents a global health problem. It ranks ninth in worldwide cancer incidence. In Egypt, carcinoma of the bladder is the most prevalent cancer, Bladder cancer has the highest recurrence rate of any malignancy. Certainly, suitable molecular diagnostic markers are required to improve the early detection of bladder cancer and then to prolong survival of patients. The present study was aimed to explore the expression of CDk4 and STAT3 in bladder cancer tissues as prospective for target therapy. Our studied groups showed higher values of CDK4 and STAT3 expression in malignant tissues (SCC andUC collectively) compared to cystitis, however, significantly higher values of CDK4 and STAT3 expression were detected in UC group compared to SCC group. Urothelial carcinomas with papillary patterns showed lower parameters of CDK4 and STAT3 expression compared to the non-papillary variant, with significant differences. Higher grades of UC showed significantly higher parameters of CDK4 and STAT3 expression compared to low grade ones. Muscle invasion increases the level of CDK4 and STAT3 expression parameters, compared to non-muscle invasive UC. Conclusion: Our results showed a good correlation of the expression patterns of both the cell cycle (CDK4) and inflammatory (STAT3) markers studied and might be helpful for suggesting more selective agents in the therapeutic scenario of bladder cancer in the near future. Potential biomarkers such as CDK4 andSTAT3 may be targets for molecular based therapeutic strategies in the prevention or management of bladder cancer. Future studies should explore molecular mechanisms of these proteins to define their roles in tumorigenesis.

Rutin and Selenium Co-administration Reverse 3-Nitropropionic Acid-Induced Neurochemical and Molecular Impairments in a Mouse Model of Huntington's Disease.

Systemic administration of 3-nitropropionic acid (3-NPA) is commonly used to induce Huntington's disease (HD)-like symptoms in experimental animals. Here, the potential neuroprotective efficiency of rutin and selenium (RSe) co-administration on 3-NPA-induced HD-like symptoms model in mice was investigated. 3-NPA injection evoked severe alterations in redox status, as indicated via increased striatal malondialdehyde and nitric oxide levels, accompanied by a decrease in levels of antioxidant molecules including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Moreover, 3-NPA potentiated inflammatory status by enhancing the production of interleukin-1ß, tumor necrosis factor-α, and myeloperoxidase activity. Pro-apoptotic cascade was also recorded in the striatum as evidenced through upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. 3-NPA activated astrocytes as indicated by the upregulated glial fibrillary acidic protein and inhibited brain-derived neurotrophic factor. Furthermore, perturbations in cholinergic and monoaminergic systems were observed. RSe provided neuroprotective effects by preventing body weight loss, oxidative stress, neuroinflammation, and the apoptotic cascade. RSe inhibited the activation of astrocytes, increased brain-derived neurotrophic factor, and improved cholinergic and monoaminergic transmission following 3-NPA intoxication. Taken together, RSe co-administration may prevent or delay the progression of HD and its associated impairments through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory effects.

Pancreatic transplantation: Brief review of the current evidence.

Kidney transplantation is the treatment of choice for management of end-stage renal disease. However, in diabetic patients, the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation. Pancreatic transplantation in humans was first introduced in 1966. The initial outcome was disappointing. However, this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies. Combined kidney and pancreas transplantation will not only solve the problem of organ failure, but it will also stabilise or even reverse the metabolic complications of diabetes. Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure. Nevertheless, at the cost of an initial increase in morbidity and risk of mortality. Other transplantation options include pancreas after kidney transplantation and islet cell transplantation. We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease. Our work will provide a simplified, yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.

The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4.

BACKGROUND: Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt. OBJECTIVE: Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy. METHODS: Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohistochemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis. RESULTS: The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each). CONCLUSION: The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy.

Association of serum level of vitamin D and VDR polymorphism Fok1 with the risk or survival of pancreatic cancer in Egyptian population.

BACKGROUND AND AIMS: Pancreatic cancer (PC) is the fourth most common cause of death from cancer in Egypt. Few studies have been conducted to assess the relationship between vitamin D serum level and vitamin D receptor (VDR) polymorphisms with the survival of PC patients. This is the first study in Egypt to investigate the association of the status of vitamin D serum level and genotypic distribution of single nucleotide polymorphisms (SNP) Fok1 with the risk of developing PC and whether they could detect survival or not. PATIENTS AND METHODS: The study included a total of 47 PC cases that were histopathologically proven to have PC, and 37 controls that were attending at the same time for investigation but proved that they were all PC free. Pre-diagnostic concentrations of vitamin D and VDR polymorphism Fok1 were assessed from all participants in the study. RESULTS: There was a 1.5-fold increase in the serum level of vitamin D in PC patients when compared to non-PC subjects. Regarding VDR Fok1, polymorphism distribution in PC was CC (Wild Type) 26 (55.3%), CT 16 (34%), and TT 5 patients (10.7%). For the control group, CC was found in 24 (64.8%), CT in 12 (32.4%), and TT genotype was found only in one individual 1 (2.8%) with no statistically significant difference between the two studied groups (P 0.72). CONCLUSION: Low serum vitamin D or VDR-SNP is not a risk factor for PC in Egyptian patients. Recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer and improving overall survival should be carefully considered.

The synthesis and characterization of zinc-containing electrospun chitosan/gelatin derivatives with antibacterial properties.

Homogenous allocation of inorganic particles in a polymeric matrix is a challenge. In this work, we discuss electrospinning of chitosan /gelatin using CS-Si (chitosan silicone hybrids) as well as the formation of homogeneously distributed Zn elements inside chitosan nanofiber through chitosan -GPTMS hybrids. Chitosan -GPTMS hybrids can be synthesized by acid catalyzed amino-oxirane addition reaction. The proposed mechanism was approved by using spectral and elemental analyses. The chitosan derivative Si-Cs was mixed with gelatin and their solution were applied to electrospinning. Optimization of spinning process is reached. A homogeneous spinnable solution with desirable properties is obtained by addition of Zinc acetate. The characterizations of the spinnable solution in term of electrical conductivity and viscosity were studied. Characterization of the nanofiber formed by SEM show that there is no Zn accumulated on the nanofiber surfaces which is one of the advantages of introducing GPTMS to Cs chain. The superior antibacterial activity of the produced zinc-containing electrospun fibers of Gelatin-Si-Cs nominate it to be applied for medical purpose.

Antitumor Potential of Berberine and Cinnamic Acid against Solid Ehrlich Carcinoma in Mice.

BACKGROUND: Berberine and cinnamic acid are natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. OBJECTIVE: In the present study, we aimed to investigate the proapoptotic potential of cinnamic acid and berberine in cancer cells by examining their effect on the expression of proapoptotic and antiapoptotic genes. Moreover, the effects of berberine and cinnamic acid on the antitumor activity of cisplatin were investigated in Ehrlich solid tumor-bearing mice. METHODS: For the study, 90 male mice were inoculated intramuscularly with Ehrlich ascites tumor cells (2.5 × 106/mouse), and then on day 4, mice were randomly divided into six experimental groups (group 1-untreated Ehrlich solid tumor (EST), group 2-EST treated CDDP, group 3-EST treated CA, group 4-EST treated BER, group 5-EST treated CA + CDDP, and group 6-EST treated BER + CDDP). RESULTS: The results showed that berberine and cinnamic acid significantly decreased tumor growth and tumor volume (-74.8 and -75.5%, respectively) both as single agents and in combination with cisplatin. Moreover, both berberine and cinnamic acid increased the ratio of tumor growth inhibition (-91.5 and -92.6%, respectively), mean survival time (61.5 and 26 days, respectively), and percentage increase in lifespan (559 and 263%, respectively) of the treated mice. Our results also showed that both berberine and cinnamic acid-induced apoptosis by increasing the Bax/Bcl-2 ratio (74.1 and 45.1, respectively) and caspase-3 expression (14.3- and 11.6-fold increase, respectively). Additionally, berberine and cinnamic acid decreased oxidative stress markers, as shown by the decrease in lipid peroxidation and nitric oxide levels and an increase in reduced glutathione level. CONCLUSION: These results suggest that berberine and cinnamic acid have potential as antitumor and antioxidant agents derived from natural sources, which could be used alone or in combination with regular chemotherapeutic agents, such as cisplatin. These effects could be attributed to the proapoptotic activity of berberine and cinnamic acid.

Utility of central venous pressure measurement in renal transplantation: Is it evidence based?

Adequate intravenous fluid therapy is essential in renal transplant recipients to ensure a good allograft perfusion. Central venous pressure (CVP) has been considered the cornerstone to guide the fluid therapy for decades; it was the only available simple tool worldwide. However, the revolutionary advances in assessing the dynamic preload variables together with the availability of new equipment to precisely measure the effect of intravenous fluids on the cardiac output had created a question mark on the future role of CVP. Despite the critical role of fluid therapy in the field of transplantation. There are only a few clinical studies that compared the CVP guided fluid therapy with the other modern techniques and their relation to the outcome in renal transplantation. Our work sheds some light on the available published data in renal transplantation, together with data from other disciplines evaluating the utility of central venous pressure measurement. Although lager well-designed studies are still required to consolidate the role of new techniques in the field of renal transplantation, we can confidently declare that the new techniques have the advantages of providing more accurate haemodynamic assessment, which results in a better patient outcome.

Smoking in Renal Transplantation; Facts Beyond Myth.

Smoking is one of the preventable leading causes of death worldwide. Most of the studies focused on the association between smoking and cardiovascular disease, pulmonary diseases, malignancy and death. However, the direct effect of smoking on the renal system was undermind. There are emerging evidence correlating tobacco use with pathological changes in the normal kidneys. The effect is more obvious on the renal allograft most probably due to the chronic immune suppression status and the metabolic effect of the drugs. Several studies have documented a deleterious effect of smoking on the renal transplant recipients. Smoking was associated with lowering patient and graft survival. Smoking cessation proved to improve graft survival and to a lesser extent recipient survival. Even receiving a renal transplant from a smoker donor increases the risk of death for the recipient and carries a poorer graft survival compared to non-smoking donors. Most of the studies investigating the effect of smoking were based on self-reporting questioners, which may be misleading due to poor recall or the desire to give socially acceptable answers. This made the need of a reliable biomarker of ultimate importance. Cotinine was proposed as a promising biomarker that may help to provide objective evidence regarding the status of smoking and the dose of nicotine exposure, yet there are still some limitations of its use. The aim of this work is to review the current evidence to improve our understanding of this critical topic. Indeed, this will help to guide better-designed studies in the future.

Randomized, double-blind, placebo-controlled trial to compare solifenacin versus trospium chloride in the relief of double-J stent-related symptoms.

PURPOSE: We aimed to compare the safety and efficacy of solifenacin versus trospium chloride and compare each drug versus placebo regarding the relief of stent-related symptoms following uncomplicated ureteroscopic lithotripsy (URSL). METHODS: In a prospective, randomized, double-blind study, 210 eligible patients who underwent URSL with double-J stent insertion were recruited and randomly assigned to either the first group, receiving solifenacin (10 mg), second group, receiving trospium chloride (60 mg), or the third group, receiving placebo (one tablet). All patients were kept on study medication once daily during the entire 2-week postoperative period. All subjects were asked to complete a brief-form questionnaire to assess the lower urinary symptoms, stent-related body pain and hematuria, preoperatively and 2 weeks postoperatively. RESULTS: There were no statistically significant differences among the study groups in terms of mean age, gender, anthropometric measurements, stone and stent criteria. The overall symptom score, urgency, urge incontinence, flank pain, urethral pain and gross hematuria scores were significantly lower in solifenacin group compared to trospium chloride and placebo groups (p < 0.001). Concerning frequency and nocturia, there was no significant difference in mean scores across all groups. Drug-related side effects, particularly constipation, were higher in trospium group than in solifenacin one. CONCLUSIONS: Solifenacin treatment showed significant improvement in almost all domains of stent-related symptoms than trospium. In terms of safety and tolerance, both drugs were comparable. Future studies should be designed to address the impact of combined drugs and lower doses in the management of DJ stent-related symptoms.

Evaluation of circulating ADH and MIC-1 as diagnostic markers in Egyptian patients with pancreatic cancer.

BACKGROUND: Despite the incidence rate of pancreatic cancer (PC) is uncommon in developing countries, it is considered as one of the most lethal disease. Improving patients' survival requires diagnosis of the disease at early stage. Therefore, it is imperative to identify more specific and sensitive marker(s) to be used for early detection of PC. OBJECTIVES: Our aim is to evaluate the potential role of circulating ADH and MIC-1 to be used as diagnostic markers in Egyptian patients and assess their value either alone or combined with CA19-9 in early detection of PC. METHODS: Alcohol dehydrogenase (ADH), macrophage inhibitory cytokine (MIC-1) and CA19-9 were measured by ELISA in serum procured from PC patients (n = 50) versus normal subjects (n = 20). RESULTS: Our results demonstrate that the circulating levels of ADH, MIC-1 and CA19-9 in blood of PC were significantly higher than in healthy controls (HCs) (p < 0.001). The highest marker sensitivity observed at early stage was MIC-1 (90%) and specificity was ADH (83%). The level of all three markers was elevated significantly in early stage of PC in comparison to HCs. The addition of ADH and MIC-1 to CA19-9 significantly improved the efficacy of diagnosis (p = 0.023). CONCLUSION: Our data demonstrate that not only the combination of ADH and MIC-1 to CA19-9 can be used in early detection of PC but also can improve the overall quality of diagnosis of this lethal disease.

The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity.

This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5 mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200 mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity.