HEPATOPROTECTIVE ACTIVITY OF MONASCUS PURPUREUS (RED RICE YEAST) IN DIABETIC RATS ALONE OR IN COMBINATION WITH PIOGLITAZONE: AN EFFECT MEDIATED THROUGH CYTOKINES, ANTIOXIDANTS AND LIPID BIOMARKERS

Objective: Diabetes induces many complications such as cardiovascular problems, cataracts, kidney damage and polyneuropathy. Streptozotocin (STZ) induced diabetes is considered one of the most common animal models in rats. The present study investigated the effects of Monascus purpureus (MP) alone or in combination with pioglitazone on glucose level and on liver in streptozotocin (STZ) diabetic rats.Methods: In this study were divided into five experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with Monascus purpureus (500 mg/kg B. W, oral), treated STZ-diabetic with pioglitazone (10 mg/kg B.W., oral) and treated STZ-diabetic with MP (250 mg/kg B. W, oral)+pioglitazone (10 mg/kg B.W., oral)). Treatment continued for 14 d then blood sampling was done to assess blood glucose. At the end of the study, the animals were fasted overnight, anesthetized with sodium pentobarbital (60 mg/kg i.p.), and sacrificed to collect tissues samples (liver, pancreases).Results: Throughout the experimental period, all treatments significantly (P<.05) lowered serum glucose, triglycerides, cholesterol, c-peptide and IL-6. In addition, hepatic cholesterol and triglycerides levels were also lowered. Moreover, the treated diabetic rats showed higher activity of reduced glutathione (P<.05) in the liver compared with the diabetic control rats and inhibited diabetes induced elevation in the level of malondialdehyde in liver.Conclusion: The results of this study clearly demonstrated that MP act by many ways, including anti-hyperglycemic, antioxidant effects and pancreatic β-cell protection. From these points, it seems that MP may be a useful supplement to alleviate the development of diabetes and its complications

Tumor-Associated Macrophage (TAM) and Angiogenesis in Human Colon Carcinoma

AIM: This study aimed to clarify how macrophages affect prognosis in cancer colon and their association with tumor angiogenesis.MATERIAL AND METHODS: Forty four biopsies of colon carcinoma and 15 of benign adenomatous polyps were investigated for macrophages infiltration and microvessels density using immunohistochemistry and image morphometric analysis. Macrophages and blood vessels were stained immunohistochemically by CD68 and F-VIII markers respectively. The morphometric analysis was carried out on the immunohistochemically stained slides using the Leica Qwin 500 Image Analyzer. Both of macrophages infiltration and microvessels density were correlated with histological tumor grade, stage and lymph node metastases and were correlated with each others.RESULTS: Macrophage infiltration was significantly higher in malignant cases than in benign polyps. High macrophage infiltration and hypervascularity were significantly correlated with T-staging and lymph nodes metastasis. A significant correlation was found between macrophage infiltration and microvessels densitie in malignant tumors where hypervascularity was significantly correlated with high macrophages infiltration.CONCLUSION: The significant correlation between macrophage infiltration and tumor angiogenesis suggests an interaction between macrophages and cancer cells stimulating microvessels formation, tumor invasion and metastasis in colon cancer. We recommend that macrophages infiltration should be evaluated to investigate their clinical value in development of individualized therapeutic regimens for management of colon carcinoma

DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue.AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours.MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis.RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001).There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups.CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours

Detection of Cancer Stem Cells in Colorectal Cancer: Histopathological and Immunohistochemical Study

BACKGROUND: Growing evidence supports the notion that the onset of tumorigenesis could occur through cancer stem cells (CSCs). These tumour cells show low proliferative rates, high self-renewal capacity, propensity to differentiate into active proliferating tumour cells & resistance to chemoradiotherapy thus, possibly causing local recurrences & metastasis formation. CD44 has been used as a marker to isolate CSCs from colorectal carcinoma (CRC).AIM: To investigate the immunohistochemical expression of cancer stem cells marker (CD44) in CRC and correlate its expression with the clinicopathological aspects, TNM staging and modified Dukes’ classification.MATERIALS AND METHODS: Tumour biopsies from colectomy specimens of 60 patients with CRC were stained with hematoxylin-eosin for histological evaluation then immunostained with monoclonal antibodies against CD44 which was detected in term of negative or positive expression.RESULTS: CD44 was demonstrated in 58.3% (35/60) of cases and showed statistically significant correlation with tumour site and histological type (p-value < 0.05). However, CD44 showed statistically insignificant inverse correlation with tumour invasiveness (T), lymph node status (N), grade, TNM stage grouping and modified Dukes’ classification, while it was directly correlated with distant metastasis (M) (p-value > 0.05). Chi-square /Fisher exact test proportion independence and the p-value are set significant at 0.05 level.CONCLUSION: the CD44 rate of expression is higher in the colon than rectum and in adenocarcinoma than mucinous and undifferentiated carcinoma. CD44 showed statistically insignificant relation with T, N, M, grade, TNM stage grouping and modified Dukes’ classification

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma

Abstract The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The induced tumors were examined by needle biopsy. A targeted anticancer drug (Cetuximab) and [Cisplatin and 5 Fluorouracil (5-FU)] chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. FTIR peaks identified the polymeric structure of the drug nano-carrier. Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X2 = 12.63, P < 0.001). Finally, using synthesized PEG–PLA–PEG NPs for intralesional injection is a promising route for the treatment of OSCC

Gamma-aminobutyric acid ameliorates gamma rays-induced oxidative stress in the small intestine of rats

Abstract Background The current study aimed to evaluate the role of gamma-amino butyric acid (GABA) in modulating histopathological and biochemical disturbances in the rat’s small intestine following gamma radiation exposure. Results The results showed that whole body gamma irradiation (6 Gy) of rats induced mucosal damage, hemorrhage, increased cellularity of the lamina propria layer with areas of complete ulcerations. Histopathological changes were associated with a significant increase in malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). In parallel, a significant decrease in catalase (CAT) and glutathione peroxidase (GSH-Px) activities was demonstrated. Administration of GABA (200 mg/kg body weight GABA daily via gastric gavage for three consecutive weeks) after irradiation of rats has significantly improved the oxidant/antioxidant status which was associated with regeneration of the small intestinal cell structure. Conclusion Gastric administration of GABA was found to offer an advantageous treatment against gamma irradiation-induced small intestine oxidative stress in rats, probably by utilizing ameliorative effects via its antioxidant and free radical-scavenging activities. Its mechanisms need to be further investigated

Immunohistochemical expression of CD163 in colorectal carcinoma and its prognostic value

Background/aim Colorectal cancer (CRC) is one of the most frequent cancers worldwide with one of the highest mortality rate. CD163 is a 130-KDa transmembrane protein, known to be involved in hemoglobin clearance by functioning as a receptor for hemoglobin–haptoglobin complex. Several studies have demonstrated that CD163 is expressed on some cancer cells, and its expression is associated with poor clinical prognosis. This study aimed to evaluate CD163 to assess the distribution of macrophages in invasive margins and intratumoral infiltration area, using computerized image analysis, to evaluate its prognostic value and its association with other clinicopathological characteristics in colorectal carcinoma. Patients and methods The present study enrolled 80 formalin-fixed paraffin-embedded CRC surgical specimens, obtained from the Department of Pathology of National Research Centre, Egypt, and examined for the expression of CD163 in CRCs by immunohistochemical techniques. The morphometric analysis was done on the invasive margins and intratumoral infiltration area in each slide. Results The study cases of colorectal carcinoma patients, 46 (57.5%) cases were diagnosed as adenocarcinoma and rest 34 (42.5%) cases were mucinous carcinoma. Twenty-two cases (22/80) showed a low intratumoral infiltration area and moderate invasive margin. CD163+ intratumoral infiltration significantly correlated with age, tumor site, tumor type, lymph node status, and metastasis. On the other hand, CD163+ invasive margins significantly correlated with tumor grade, tumor classification, metastatic status, tumor stage, and Duke’s classification. Conclusion Invasive front of the tumor is the most suitable area for the evaluation of tumor-associated macrophages that is important in detecting prognostic prediction of colon cancer and its clinical outcome. So, it can be considered as an ideal prognostic marker in the treatment of colon cancer

The Relation between Serum C-peptide Levels and Diabetic Retinopathy in Type 1 Diabetic Patients in an Egyptian population: An observational retrospective study The Relation between Serum C-peptide Levels and Diabetic Retinopathy in Type 1 Diabetic Patien

Abstract: Objective: The aim of the study is to confirm the relationship between low serum C-peptide levels and microvascular diabetic complication, especially diabetic retinopathy in Type 1 diabetics in the Egyptian population. Research Design and Methods,20 type 1 Egyptian diabetic patients (9 males and 11 females) were selected and included, matching demographic criteria (average age of 18 years, range 14 -22) and all were diagnosed having diabetes for about 5 years duration (range 4.7 -6.2). All recruited patients were followed during the 5 years by regular follow-up visits, a visit every 4 months (3 visits per year). Serum C-peptide and Fundus Examination were estimated twice, at year 1 (recruitment period) and at year 5 at the end of the study. Results: At the end of our retrospective observational study period (5years) and among the 20 followed patients, 3 patients (15%) -all females -developed moderate NPDR changes, all 3 subjects had very low undetectable serum C-peptide levels (0.01-0.15 ng/ml) (p&lt;0.01)5 patients (25 %) -2 males and 3 females -developed mild NPDR changes, all 5 subjects had a low serum C-peptide level average 0.2 ng/ml (range 0.15 -0.3) (p&lt;0.01).No diabetic retinopathy changes could be detected by fundus examination in the remaining 12 patients (60%) at the end of the study period. All 12 subjects had an average serum C-peptide level of 0.4 ng/ml (range 0.2 -0.7). Average HbA1c level among all patients, was 7.3% (range 6.5-7.8%). It did not correlate much with the incidence of DR and it was not statistically significant. (p&lt;0.5).Conclusion: Diabetic retinopathy is a serious disabling microvascular diabetes complication. Early detection plays a major role for its prevention and prognosis. C-peptide levels could be a valuable diagnostic tool for the prediction of this diabetes complication and deserves more awareness among the healthcare providers for the benefit of our patients

Childhood glaucoma profile in Dakahelia, Egypt: a retrospective study

AIM: To analyze childhood glaucoma regarding its demographics, presentations, different causes and surgical modalities used among patients in Dakahelia and to apply the Childhood Glaucoma Research Network (CGRN) classification retrospectively to evaluate its convenience. METHODS: A retrospective study in which the medical files of all glaucoma patients <16 years old presented to Mansoura Ophthalmic Center, Mansoura University from 2014 to 2017, were retrieved and analyzed. Collected data included: age, gender, laterality, visual acuity (VA), refraction, intraocular pressure (IOP), corneal diameter, cup-disc ratio, types and number of surgeries and antiglaucomatous drugs (AGD) at the first and last visit. Prevalence of different subtypes was calculated and means of clinical features were compared. RESULTS: A total of 305 eyes of 207 patients were included classified into 6 groups: primary congenital glaucoma (PCG), juvenile open angle glaucoma (JOAG), glaucoma associated with systemic disease, glaucoma associated with ocular anomalies, acquired glaucoma and glaucoma following cataract surgery. PCG was the predominant type (55.1%) followed by acquired glaucoma (29.5%). Males represented 63.8% of the whole studied patients. Glaucoma associated with ocular anomaly group showed the youngest age at diagnosis (21.9±30.0mo). The shortest corneal diameter was recorded in post cataract group (10.4±0.5 mm). Highest cup-disc ratio was found in the PCG group (P<0.0005). Glaucoma associated with systemic disease presented with the highest baseline IOP (34.5±5.0 mm Hg). All the cases with PCG were treated surgically with 21.8% required more than one surgery. The majority of the patients (74.2%) in the acquired group were treated medically. Combined trabeculotomy-trabeculectomy was the most frequent operation done, accounting for 34.5% of all primary surgeries. Ahmed valve implantation comprised 87% of the secondary surgeries. Acquired glaucoma group had the highest percent of eyes with good final Snellen's VA (69.4%), while glaucoma associated with ocular anomaly group had poorest final VA. CONCLUSION: PCG is the most prevalent type of childhood glaucoma, followed by acquired glaucoma especially traumatic hyphema. Combined trabeculotomy-trabeculectomy and Ahmed valve implantation are the most common surgical interventions. CGRN classification is found to provide a consensus skeleton and is recommended to be integrated in our routine ongoing clinical practice

Regression of fibrosis by cilostazol in a rat model of thioacetamide-induced liver fibrosis: Up regulation of hepatic cAMP, and modulation of inflammatory, oxidative stress and apoptotic biomarkers.

In liver fibrosis, conversion of fibroblasts to profibrogenic myofibroblasts significantly drives the development of the disease. A crucial role of cyclic adenosine monophosphate (cAMP) in regulation of fibroblast function has been reported. Increase in cAMP levels has been found to decrease fibroblast proliferation, inhibit their conversion to myofibroblast, and stimulate their death. cAMP is generated by adenyl cyclase (AC), and degraded by cyclic nucleotide phosphodiesterase (PDE). In this study, the antifibrotic effect of a PDE inhibitor, cilostazol (Cilo), on a rat model of liver fibrosis induced by thioacetamide (TAA) was investigated. Four groups of rats were used; the first group received the vehicles and served as the normal control group, while liver fibrosis was induced in the other groups using (TAA, 200 mg/kg/biweekly for 8 successive weeks, ip). The last two groups were treated with Cilo (50 and 100 mg/kg/day, po, respectively). Induction of liver fibrosis in TAA-treated rats was observed as evidenced by the biochemical and histopathological findings. On the other hand, a potent antifibrotic effect was observed in the groups treated with Cilo, with preference to the higher dose. In these groups, a significant increase in the liver content of cAMP was demonstrated that was accompanied by reduction in the hepatic expression of key fibrogenic cytokines, growth factors, and inflammatory biomarkers, including interleukin-6, tumor necrosis factor-alpha, nuclear factor kappa B, and transforming growth factor-beta as compared to TAA group. Moreover, amelioration of TAA-induced oxidative stress and apoptosis in the liver has been observed. These findings reveal the antifibrotic effect of Cilo against TAA-induced liver fibrosis in rats, and suggest regulation of cAMP pathway, together with the modulation of oxidative stress, inflammation, and apoptosis as mechanistic cassette underlines this effect