PROTECTIVE EFFECT OF SOME CHELATING AGENTS AND ANTIOXIDANTS ON THE BIOHAZARDS PRODUCED FROM WATER POLLUTION BY HEAVY METALS IN WISTAR RATS: BIOLOGICAL, GENETIC AND HISTOPATHOLOGICAL STUDY

Background: Heavy metals that normally cause problems are mercury (HgCl2) and lead acetate (LA). Chelating and inhibitor agents are the target to treat and overcome metal toxicity. The current study has been carried out to evaluate the protective effects of N-acetyl cysteine (NAC) and meso 2,3 dimercaptosuccinic acid (DMSA) against HgCl2 and LA toxicity. Materials and Methods: Ninety male Wistar rats were divided into nine equal groups. The groups were administered NAC and/or DMSA in presence or absence of LA (LA; 0.2% in drinking water) or HgCl2 (2 mg/kg BW) for 2 consecutive months. Serum and organs were collected for biochemical, genetic and histopathological changes. Results: Biochemical results revealed that LA and HgCl2 significantly increased the levels of liver and kidney biomarkers. Administration of NAC and DMSA considerably improved these altered changes. LA and HgCl2 decreased serum levels of antioxidants and were ameliorated in NAC and DMSA administered rats. LA and HgCl2 administration upregulated expression of IL-1β and IL-8 that were normalized by NAC and DMSA. Kidneys of LA and HgCl2 groups showed intraluminal hyaline casts. Kidneys of DMSA-administrated rats showed mild hydropic degeneration of renal tubular epithelium in LA and HgCl2 groups. Kidneys of NAC administrated rats showed atrophy of capillary tufts. Kidneys of LA and HgCl2 administered rats which received DMSA and NAC showed normal glomerular structure. Liver histopathology showed sever changes that were ameliorated by NAC and DMSA. Conclusion: Taken together, usage of NAC and DMSA provide significant protection against LA and HgCl2-induced hepatotoxicity and nephrotoxicity in male Wistar rats

Helicobacter pylori infection might be responsible for the interconnection between type 1 diabetes and autoimmune thyroiditis

<p>Abstract</p> <p>Background</p> <p>Higher serological prevalence rates of helicobacter pylori (H. pylori) infection have been reported in patients with type 1 diabetes (T1DM) and autoimmune thyroiditis (AT). Patients with T1DM are at increased risk for developing other autoimmune diseases, most commonly AT. It is unknown whether H. pylori infection could explain the high prevalence of thyroid autoantibodies and AT in T1DM. The aim of the current study was to evaluate anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) autoantibodies in correlation with anti-H. pylori IgG and IgA in young patients with T1DM.</p> <p>Methods</p> <p>Anti-H. Pylori IgG, IgA, anti-TPO and anti-Tg antibodies titers were measured in 162 euthyroid patients with T1DM and 80 healthy controls matched for age, sex and socioeconomic status.</p> <p>Results</p> <p>Seroprevalence of H. pylori was significantly higher in patients with T1DM than in healthy controls; 79% vs. 51.2%, p < 0.001. Anti H. pylori IgG was positive in 61.1% of patients with T1DM and 30% of controls, p < 0.001, anti H. pylori IgA was positive in 74% of patients with T1DM and 32.5% of controls, p < 0.001. Thyroid autoimmunity was also significantly higher in patients with T1DM than in controls; 56.7% vs. 6.2%, p < 0.001. Anti-TPO was positive in 25.3% of patients with T1DM and 3.7% of controls, p < 0.001, anti-Tg was positive in 47.5% of patients with T1DM and 6.2% of controls, p < 0.001. With simple and multiple regression analysis anti-H. pylori IgG and IgA titers were positively and significantly correlated with Anti-TPO and anti-Tg titers in patients with T1DM.</p> <p>Conclusion</p> <p>our results support the idea of a connection between H. pylori infection and the occurrence of anti-TPO, anti-Tg autoantibodies and AT in young patients with T1DM. So, H. pylori infection could be considered as an environmental trigger for development of AT in T1DM. Young patients with T1DM should be screened for H. pylori infection.</p

The Transgene Expression of the Immature Form of the HCV Core Protein (C191) and the LncRNA MEG3 Increases Apoptosis in HepG2 Cells

Long non-coding RNAs (lncRNAs) are regulated in cancer cells, including lncRNA MEG3, which is downregulated in Hepatocellular Carcinoma (HCC). In addition, hepatitis C virus (HCV) core proteins are known to dysregulate important cellular pathways that are linked to HCC development. In this study, we were interested in evaluating the overexpression of lncRNA MEG3, either alone or in combination with two forms of HCV core protein (C173 and C191) in HepG2 cells. Cell viability was assessed by MTT assay. Transcripts&rsquo; levels of key genes known to be regulated in HCC, such as p53, DNMT1, miRNA152, TGF-b, and BCL-2, were measured by qRT-PCR. Protein expression levels of caspase-3 and MKI67 were determined by immunocytochemistry and apoptosis assays. The co-expression of lncRNA MEG3 and C191 resulted in a marked increase and accumulation of dead cells and a reduction in cell viability. In addition, a marked increase in the expression of tumor suppressor genes (p53 and miRNA152), as well as a marked decrease in the expression of oncogenes (DNMT1, BCL2, and TGF-b), were detected. Moreover, apoptosis assay results revealed a significant increase in total apoptosis (early and late). Finally, immunocytochemistry results detected a significant increase in apoptotic marker caspase-3 and a decrease in tumor marker MKI67. In this study, transgene expression of C191 and lncRNA MEG3 showed induction in apoptosis in HepG2 cells greater than the expression of each one alone. These results suggest potential anticancer characteristics

Synchronous occurrence of primary mucinous carcinoma of recto-sigmoid colon and primary breast Carcinoma: A case report and review of literature

Background: Multiple primary malignant tumors (MPMTs) is simultaneous occurrence of two or more malignancies in different sites with different histopathological type and origin.Diagnosis and management of those patients are challenging due to uncertain guidelines. Case Presentation: A 63-year-old postmenopausal female patient of synchronous MPMTs in which the patient was diagnosed with a malignant mass in recto-sigmoid colon and a synchronous breast cancer was incidentally discovered during clinical and radiological patient evaluation. Treatment: Both colon procedure and breast procedure were performed together in one setting. The anterior resection of the reco-sigmoid mass and colocolonic anastomosis were done. Conclusion: Synchronous colon and breast cancer treatment plan should be individualized for each patient through a complete preoperative evaluation and MDT meeting to provide the best possible treatment for the patient

Role of orbital magnetic resonance imaging in early detection of graves’ orbitopathy and disease activity

Background and aim: we aim to evaluate feasibility of using diffusion tensor imaging (DTI) "A new technique of magnetic resonance imaging (MRI)", of extraocular muscles (EOMs) in patients with Graves’ orbitopathy (GO) versus clinical activity score (CAS) in early detection of GO activity. Methods and materials: This case control study was conducted on 20 patients with moderate to severe active GO (10 males &amp; 10 females with a mean age of 35.50±13.65 years) and 10 age and sex-matched volunteers without any thyroid abnormality as a health control (HC). Patients and HCs underwent DTI of the orbit in coronal plane. Mean diffusivity (MD) of each of the EOMs was calculated. CAS, according to the standardized criteria recommended by European Group on Graves’ Orbitopathy (EUGOGO), was calculated for the patients. Results: GO patients’ EOMs showed significantly higher MD values compared to HCs’ (P &lt; 0.001). Median CAS was 4. A statistically significant positive correlation was only detected between CAS and MD of the inferior rectus muscle (r=.360, p=.023). Conclusion: DTI is a useful tool for detecting microstructural changes in GO and superior to CAS in early detection of GO activity

Effects of Karela (Bitter Melon; Momordica charantia) on genes of lipids and carbohydrates metabolism in experimental hypercholesterolemia: biochemical, molecular and histopathological study

Abstract Background Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used. Methods Forty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela. The treatments continued for 10 weeks. Karela was given for hypercholesterolemic rats after 6 weeks of cholesterol administration. Serum, liver and epididymal adipose tissues were taken for biochemical, histopathological and genetic assessments. Results Hypercholesterolemia induced a decrease in serum superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and an increase in malondialdehyde (MDA) levels that were ameliorated by karela administration. Hypercholesterolemia up regulated antioxidants mRNA expression and altered the expression of carbohydrate metabolism genes. In parallel, hypercholesterolemic groups showed significant changes in the expression of PPAR-alpha and gamma, lipolysis, lipogenesis and cholesterol metabolism such as carnitine palmitoyltransferase-1 (CPT-1). Acyl CoA oxidase (ACO), fatty acids synthase (FAS), sterol responsible element binding protein-1c (SREBP1c), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1) at hepatic and adipose tissue levels. Interestingly, Karela ameliorated all altered genes confirming its hypocholesterolemic effect. Histopathological and immunohistochemical findings revealed that hypercholesterolemia induced hepatic tissue changes compared with control. These changes include cholesterol clefts, necrosis, karyolysis and sever congestion of portal blood vessel. Caspase-3 immunoreactivity showed positive expression in hepatic cells of hypercholesterolemic rats compared to control. All were counteracted and normalized after Karela administration to hypercholesterolemic group. Conclusion Current findings confirmed that karela is a potential supplement useful in treatment of hypercholesterolemia and its associated disorders and is good for human health

Vascular cell adhesion molecule-1 (VCAM-1), flow mediated dilatation (FMD) and carotid intima media thickness (IMT) in children with juvenile idiopathic arthritis: Relation to disease activity, functional status and fatigue

Background: There is risk of premature atherosclerosis in juvenile idiopathic arthritis (JIA) patients which predisposes to cardiovascular disease (CVD) in adulthood. This can be assessed by flow mediated dilatation (FMD) and carotid intima media thickness (IMT) of the arterial wall and by soluble vascular cell adhesion molecule (sVCAM-1). Aim of the work: To assess endothelial dysfunction in JIA children and to correlate sVCAM with FMD of brachial artery and carotid IMT. Patients and methods: The study was conducted on 55 JIA patients. The following was assessed: body mass index (BMI), blood pressure, juvenile arthritis disease activity score (JADAS27). Childhood Health Assessment Questionnaire (C-HAQ), physical activity questionnaire (PAQ), fatigue assessment using The Pediatric Quality of Life (PedsQL) inventory, full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), serum creatinine and lipid profile, sVCAM-1, FMD and IMT. Results: The patients’ age was 10.9 ± 3.9 years and were 28 (50.9%) females. JADAS-27 and CRP was higher in systemic JIA, but fatigue scores were significantly lower. CHAQ was significantly lower in patients with polyarticular disease. Patients with high disease activity had significantly younger age of onset, lower BMI, shorter disease duration, lower fatigue scale and physical activity scores and higher CHAQ. sVCAM-1 significantly correlated with CHAQ, low-density lipoprotein, CRP and ESR while FMD significantly correlated with PedsQL and PAQ. Conclusion: JIA patients had impaired endothelial function and increased cIMT with increased sVCAM-1, impaired lipid profile, decreased physical activity and increased fatigue with a potentially higher cardiovascular risk in this pediatric population. Keywords: Vascular cell adhesion molecule-1 (sVCAM-1), Flow mediated dilatation (FMD), Carotid intima media thickness (IMT), Juvenile idiopathic arthritis, JADAS27, CHA

Outcomes of Radiofrequency Ablation for Solitary T1a Renal Cell Carcinoma: A 20-Year Tertiary Cancer Center Experience

Background: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). Materials and methods: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan–Meier method. Results: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien–Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. Conclusions: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes

Outcomes of Radiofrequency Ablation for Solitary T1a Renal Cell Carcinoma: A 20-Year Tertiary Cancer Center Experience

Background: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). Materials and methods: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (&lt;4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan&ndash;Meier method. Results: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien&ndash;Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. Conclusions: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes