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.

BK polyomavirus association with colorectal cancer development.

The development of human neoplasms can be provoked by exposure to one of several viruses. Burkitt lymphoma, cervical carcinoma, and hepatocellular carcinoma are associated with Epstein-Barr, human papilloma, and hepatitis B virus infections, respectively. Over the past three decades, many studies have attempted to establish an association between colorectal cancer and viruses, with debatable results. The aim of the present research was to assess the presence of BK polyomavirus (BKV) DNA and protein in colorectal cancer samples from patients in the Western Province of Saudi Arabia. DNA extracted from archival samples of colorectal cancer tissues was analyzed for BKV sequences using polymerase chain reaction (PCR)-based techniques. In addition, expression of a BKV protein was assessed using immunohistochemical staining. None of the tumor and control samples examined tested positive for BKV DNA in PCR assays. Furthermore, immunohistochemical staining failed to detect viral proteins in both cancer and control specimens. These results may indicate that BKV is not associated with the development of colorectal adenocarcinoma in patients in the Western Province of Saudi Arabia.

GSTM1 gene polymorphism and the risk of colorectal cancer in a Saudi Arabian population.

The enzyme glutathione S-transferase Mu 1 (GSTM1) is encoded by the GSTM1 gene. Polymorphisms in GSTM1 affect the detoxifying function of the enzyme variants. This forms the basis of the debate about the impact of the GSTM1 null/present genotype on colorectal carcinoma risk. We tested the potential influence of GSTM1 polymorphisms on the development of colorectal cancer. DNA extracted from 83 samples taken from patients that were previously diagnosed as having colorectal carcinoma and from 35 control subjects who did not have colorectal carcinoma were amplified. GSTM1 genotypes were determined by DNA sequencing. The current study revealed that the majority (69/83, 83%) of colorectal cancer cases harbored the null genotype (GSTM1*0/*0), and the remaining 14 (17%) cases harbored either the GSTM1wt/wt or the GSTM1wt/*0 genotype. In contrast, among the control cases, 23 (65%) had the null genotype (GSTM1*0/*0) and 12 (35%) had either the GSTM1wt/wt or the GSTM1wt/*0 genotype. The current report emphasizes the impact of the GSTM1 null genotype on the increased risk of colorectal carcinoma in Saudi Arabia.

Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction.

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase-1 (HO-1), Nrf2, NF-B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant increase in NF-Ò ß, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1, and Nrf2 gene expression, and a significant decrease in NF-Ò ß, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.

Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κß and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κß, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κß, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

Treatment of oral ulcers in dogs using adipose tissue-derived mesenchymal stem cells.

AIM: Adipose tissue Derived Mesenchymal Stem cells (ADMSCs) represent a promising toolfor new clinical concepts in supporting cellular therapy. The goal of this study was to investigate the effects of ADMSCs transplantation on oral ulcer healing in dogs. STUDY DESIGN: Mesenchymal stem cells were isolated from adipose tissues of dogs obtained by suction-assisted lipectomy (liposuction), by dish adherence and were expanded in culture. Oral ulcers were induced by topical application of formocresol in the oral cavity of 18 dogs. The dogs were classified into 3 groups. Either autologous ADMSCs, Corticosteriod (Dexamethasone) or vehicle (saline) was injected. The healing process of the ulcer was monitored histopathologically. Gene expression of vascular endothelial growth factor (VEGF), platelets derived growth factor (PDGF), epidermal growth factor (EGF) and collagen was assessed in biopsies obtained from all ulcers "as healing markers'", by real time polymerase chain reaction (PCR). RESULTS: ADMSCs group showed significantly accelerated oral ulcer healing compared with the Dexamethasone and control groups. There was increased expression of VEGF PDGF EGF and collagen genes in ADMSCs-treated ulcers compared with Dexamethasone and controls. CONCLUSION: ADMSCs transplantation may help accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF and PDGF as well as epithelial and connective tissue proliferation as evidenced by increased EGF and collagen gene expression.

Towards gene therapy of postoperative adhesions: fiber and transcriptional modifications enhance adenovirus targeting towards human adhesion cells.

Postoperative abdominal/pelvic peritoneal adhesions are a major source of morbidity (bowel obstruction, infertility, ectopic gestation as well as chronic pelvic pain) in women. In this study, we screened various transduction and transcription modifications of adenovirus (Ad) to identify those that support maximal Ad-mediated gene delivery to human adhesion fibroblasts, which in turn would enhance the efficacy of this novel treatment/preventative strategy for postoperative adhesions. We transduced primary cultures of human peritoneal adhesion fibroblasts with fiber-modified Ad vectors Ad5-RGD-luc, Ad5-Sigma-luc, Ad5/3-luc and Ad5-CAV2-luc as well as transcriptional targeting viruses Ad5-survivin-luc, Ad5-heparanase-luc, Ad5-mesothelin (MSLN)-CRAd-luc and Ad5-secretory leukoprotease inhibitor (SLPI)-luc, and compared their activity to wild-type Ad5-luc. At 48 h, luciferase activity was measured and normalized to the total protein content in the cells. Among the fiber-modified Ad vectors, Ad5-Sigma-luc and among the transcriptional targeting modified Ad vectors, Ad5-MSLN-CRAd-luc showed significantly increased expression levels of luciferase activity at 5, 10 and 50 plaque forming units/cell in adhesion fibroblast cells compared with wild-type Ad5-luc (p < 0.05). Specific modifications of Ad improve their gene delivery efficiency towards human peritoneal adhesion fibroblasts. Developing a safe localized method to prevent/treat postoperative adhesion formation would have a major impact on women health.

Heme oxygenase effect on mesenchymal stem cells action on experimental Alzheimer's disease.

The objective is to evaluate the effect of heme oxygenase-1 (HO-1) enzyme inducer and inhibitor on Mesenchymal Stem Cells (MSCs) in Alzheimer disease. 70 female albino rats were divided equally into 7 groups as follows: group 1: healthy control; group 2: Aluminium chloride induced Alzheimer disease; group 3: induced Alzheimer rats that received intravenous injection of MSCs; group 4: induced Alzheimer rats that received MSCs and HO inducer cobalt protoporphyrin; group 5: induced Alzheimer rats that received MSCs and HO inhibitor zinc protoporphyrin; group 6: induced Alzheimer rats that received HO inducer; group7: induced Alzheimer rats that received HO inhibitor. Brain tissue was collected for HO-1, seladin-1 gene expression by real time polymerase chain reaction, heme oxygenase activity, cholesterol estimation and histopathological examination. MSCs decreased the plaque lesions, heme oxygenase induction with stem cells also decreased plaque lesions however there was hemorrhage in the brain. Both heme oxygenase inducer alone or with stem cells increased seladin-1 expression and decreased cholesterol level. MSCs alone or with HO-1 induction exert a therapeutic effect against the brain lesion in Alzheimer's disease possibly through decreasing the brain cholesterol level and increasing seladin-1 gene expression.

Long-term ofloxacin testicular toxicity: an experimental study.

The aim of this study was to assess the long-term toxic effect of ofloxacin on the testes and epididymides of 72 adult male albino rats. The rats were divided into group A and group B. Group A, which received ofloxacin for 14 days, was subdivided into two subgroups; LD-14 received low dose 72 mg KBW(-1) daily and HD-14 received high dose 216 mg KBW(-1) daily. Group B, which received ofloxacin for 28 days, was subdivided into two subgroups; LD-28 received 72 mg KBW(-1) and HD-28 received 216 mg KBW(-1) daily. Two matched control groups were followed up for 14 and 28 days respectively. The animals were evaluated for body weight, testicular weight, relative testicular weight, serum testosterone (T), epididymal sperm analysis (sperm count, motility, morphology, curvilinear velocity, linear velocity and linearity index) and testicular histopathology. The adverse effects of ofloxacin were correlated with increased treatment duration and/or dose. It is concluded that long-term ofloxacin has a direct detrimental effect on the testicles of albino rats at the studied doses and durations.

The role of bone marrow-derived mesenchymal stem cells in treating formocresol induced oral ulcers in dogs.

BACKGROUND: Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. In this study, the effects of MSCs transplantation on oral ulcer healing were examined. METHODS: Mesenchymal stem cells were isolated from bone marrow aspirates of dogs by dish adherence and expanded in culture. Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Either autologous MSCs or vehicle (saline) was injected around the ulcer. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by reverse transcription-polymerase chain reaction. Expression of VEGF and collagen genes was detected in biopsies from all ulcers. RESULTS: Mesenchymal stem cells expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared with controls. CONCLUSION: Mesenchymal stem cells transplantation may help accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression.

Reversal of Hepatic Fibrosis by Human CD34(+) Stem/Progenitor Cell Transplantation in Rats.

Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation. Here, we transplant UCB cells into injured liver fibrosis, investigated the hepatic potential of UCB cells both in vitro and in vivo. a CCl4 rat model with liver fibrosis was prepared. Human (UCB) CD34(+) stem cell was separated with MACS (magnetic cell sorting). Cells were cultured with and without hepatic differentiation medium. Rats were divided into 3 groups; group (1): control healthy, group (2): CCl4 injected rats and group 3: CCl4/CD34(+)injected rats with human differentiated and undifferentiated cells through intrahepatic (IH) and intravenous (IV) routes. A significant elevation was detected in serum albumin in CCl4/CD34(+) compared to the CCl4 group (p<0.001). Serum ALT, had a significant decrease of its level after administration of stem cells compared to the CCl4 group (p<0.001). However, it was still significantly higher than control (p<0.001) with no significant difference between the groups that received stem cells. Histopathological examination of liver tissue showed that stem cells have a significant antifibrotic effect. Concerning gene expression, the collagen gene (rat) was highly expressed in the CCl4 group whereas its expression was significantly decreased after administration of stem cells. Human albumin and matrix metalloproteinase (MMP2) genes were expressed in liver tissues in the groups that received stem cells. Highest expression was in the group that received un-differentiated cells I.V. human UCB CD34(+) stem cells can ameliorate liver fibrosis in rats.

Production of destomycin-A antibiotic by Streptomyces sp. using rice straw as fermented substrate.

Hundred and twenty microbial isolates could be isolated from different soil samples collected from different localities in Egypt. One of the actinomycete culture AZ-H-A5 from three cultures was found to produce a wide spectrum antimicrobial agent when cultivated on rice straw. The actinomycete AZ-H-A5 could be isolated from a soil sample collected from Helwan district, Egypt. The nucleotide sequence of the 16s RNA gene (1.5 Kb) of the most potent strain evidenced an 85% similarity with Streptomyces pseudovenezue, EU841712 and Streptomyces galilaeus. From the taxonomic features, the actinomycetes isolate AZ-H-A5 matches with Streptomyces rimosus in the morphological, physiological and biochemical characters. Thus, it was given the suggested name Streptomyces rimosus, AZ-H-A5. The parameters controlling the biosynthetic process of antimicrobial agent formation including: inoculum size, different pH values, different temperatures, different incubation period, and different carbon and nitrogen sources, potassium nitrate, K2HPO4, MgSO4.7H2O and KCl concentrations were fully investigates. The active metabolite was extracted using ethyl acetate (1:1, v/v) at pH 7.0. The separation of the active ingredient and its purification was performed using both thin layer chromatography (TLC) and column chromatography (CC) techniques. The physicochemical characteristics of the purified antibiotic viz. color, melting point, solubility, elemental analysis, spectroscopic characteristics and chemical reactions have been investigated. This analysis indicates a suggested empirical formula of C20H37N13O13. The minimum inhibition concentrations "MICs" of the purified antimicrobial agent were also determined. The purified antimicrobial agent was suggestive of being belonging to Destomycin-A antibiotic produced by Streptomyces rimosus, AZ-H-A5.

Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis.

OBJECTIVE: To study the effect of mesenchymal stem cells (MSC) on experimental liver fibrosis in rats. DESIGN AND METHOD: MSC were derived from bone marrow obtained from femoral and tibial bones of male albino rats. MSC were separated, grown, and propagated in culture for 4 weeks and were characterized morphologically and by detection of CD29 by RT-PCR. They were then infused into the tail vein of female rats that received CCl4 injection to induce liver fibrosis. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and MSC. Liver tissue was examined histopathologically and liver functions (ALT and serum albumin) were estimated for all groups. Y-chromosome gene (sry) was assessed by PCR in liver tissue of the female rats to confirm uptake of the male stem cells. Hydroxyproline content in liver tissue was assessed by chemical methods and expression of the collagen gene (type I) was detected as a marker for liver fibrosis. Results of the present study showed that MSC have a significant antifibrotic effect as evidenced by the significant decrease in liver collagen gene expression as well as the decrease in hydroxyproline content in the CCl4/MSC group (p<0.001) compared to the CCl4 group. The Y-chromosome gene (sry) was detected by RT-PCR in the CCl4/MSC group, but was not detected in control group and other groups. The CD29 gene was expressed in MSC culture, and this confirmed the efficiency of isolation and propagation of MSC in culture. With regard to liver function, there was also a significant improvement and elevation of serum albumin in the CCl4/MSC group compared to the CCl4 group (p<0.05). As regard to the liver enzyme ALT, there was a decrease of its level in the CCl4/MSC group compared to the CCl4 group. However, this was statistically nonsignificant (p>0.05). In conclusion, MSC have a potential therapeutic effect against the fibrotic process through their effect in minimizing collagen deposition in addition to their capacity to differentiate into hepatocytes.

The association of absent suspensory ligaments of the liver and Marfan syndrome.

Gastrointestinal manifestations of collagen diseases are very rare. The authors report on a patient who has features of Marfan syndrome with mobile liver caused by the absence of its suspensory ligaments. This patient presented with an acute intestinal obstruction secondary to a congenital band across the distal transverse colon. Recurrent intestinal obstruction after resection of the band necessitated the performance of partial colectomy with ileotransverse anastomosis. The patient's phenotypic features are suggestive but not diagnostic of Marfan syndrome. Nevertheless, isolated skeletal manifestations of Marfan syndrome with documented FBN1 gene mutation have been reported, suggesting the existence of milder forms of the syndrome not exhibiting the classic diagnostic criteria. The authors postulate that the absence of suspensory ligaments of the liver in this patient could be attributed to the defective connective tissue of Marfan syndrome.

Organ injury scaling system can be used to predict length of stay in patients with penetrating neck injuries.

Predicting probability of survival of trauma patients has received greater attention than predicting other trauma outcomes such as length of stay. Most trauma scoring systems depend on the anatomic description of injuries of the Abbreviated Injury Score (AIS). The recently introduced Organ Injury Scale (OIS) was developed to give more precise and comprehensive anatomic description of injuries. Unlike the AIS, it also avoids including immediate injury sequelae, such as the amount of hemorrhage. This retrospective study was performed to assess the degree of association between the sum of grades of penetrating neck injuries using the OIS and the length of hospital stay. There were 31 males and 7 females, with ages ranging from 13 to 65 years and a mean of 31 years. The length of hospital stay ranged between 1 and 34 days, with a mean of 7.0 +/- 6.5 days. There were 32 vascular, 7 esophageal, and 7 tracheal injuries. The sum of the OIS grades correlates significantly with the length of hospital stay (r = 0.78; P < 0.005). This study suggests that the OIS system can be used to predict the length of hospital stay. It proposes also that the OIS replaces similar anatomic components of the AIS-based scoring systems.

Penetrating neck trauma: lack of universal reporting guidelines.

Penetrating neck injuries constitute a heterogeneous group. Two different classifications of zones of the neck exist in trauma literature. Injuries crossing the midline are not accurately reported. Records of 50 patients with stab wounds (30), gunshot wounds (GSWs; 17), and shotgun wounds (SGWs; 3) were reviewed. Injuries involved zone I in 8 patients, zone II in 37 patients, zone III in 8 patients, posterior triangle in 6 patients, and multiple zones in 5 patients. All 11 patients with transcervical GSWs and SGWs sustained vascular or aerodigestive injuries and had longer hospital stays (14.0 +/- 2.6 days) compared with patients with other GSWs (6.6 +/- 2.0 days) and stab wounds (3.6 +/- 0.5 days). We emphasize the lethal potential of transcervical GSWs and SGWs. We suggest that these particular injuries be reported separately. We recommend the universal adoption of one system of classification of neck zones.

Delayed presentation of popliteal artery pseudoaneurysm following blunt trauma.

Popliteal artery pseudoaneurysms are not uncommon. They may result from penetrating or blunt trauma, arterial reconstructive surgery, invasive diagnostic or surgical orthopedic procedures, and perigenicular neoplasia. We report two patients with popliteal artery pseudoaneurysm diagnosed 3 months and 3 weeks, respectively, after blunt trauma. These two patients as well as many patients reported in the literature had palpable distal pulses and no obvious clinical signs of arterial injury following various forms of trauma. Arteriography in these circumstances is usually abandoned because of the low yield and the possible risk of complications. However, as we illustrate in this report, noninvasive diagnostic modalities such as duplex ultrasound and magnetic resonance arteriography are both safe and accurate for early detection of popliteal artery pseudoaneurysm. Once diagnosed, standard vascular reconstruction should be performed to prevent potential complications.