One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin improves the generation of functional β cells/islet-like cell clusters in vitro, suggesting implications for cell-based replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs and obestatin on an experimental model of type II diabetes mellitus (T2DM). Sixty male rats were divided into; group I (control group), group II (T2DM group) induced by administration of high fat diet (HFD) and injection of streptozotocin (STZ) in low dose, group III (T2DM treated with MSCs), group IV (T2DM treated with obestatin), group V (T2DM treated with MSCs and obestatin). Fasting blood glucose, C-peptide, insulin and lipid profile were measured. HOMA-IR and HOMA-β were calculated. Pancreatic expression of insulin, glucagon like peptide -1 (GLP-1) and pancreatic duodenal homeobox 1 (Pdx1) mRNA levels were measured. In addition pancreatic histological changes, insulin and Bax were analyzed by immunohistochemical examination of islets of Langerhans. Diabetic rats showed significant increase in HOMA-IR, serum glucose and lipid profile levels with significant decrease in insulin, HOMA-β, GLP-1 and Pdx1 levels. MSCs and obestatin caused significant improvement in all parameters with more significant improvement in combined therapy. The protective effects afforded by MSCs and obestatin may derive from improvement of the metabolic profile, antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.
Animals ; Blood Glucose ; Bone Marrow* ; C-Peptide ; Diabetes Mellitus ; Diet, High-Fat ; Fasting ; Gene Expression ; Genes, Homeobox ; Ghrelin* ; Glucagon ; Glucagon-Like Peptide 1 ; Humans ; In Vitro Techniques ; Insulin ; Islets of Langerhans ; Male ; Mesenchymal Stromal Cells* ; Metabolome ; Models, Theoretical ; Rats* ; RNA, Messenger ; Streptozocin

Background: Endoscopic ultrasound (EUS) tissue acquisition requires rapid on-site evaluation to improve diagnostic yield with less needle passes;however, this is not readily available in all centers, also it increases the duration and the cost of the procedure. Macroscopic on-site evaluation (MOSE) is the direct assessment of the tissue sample provided by EUS-guided fine needle biopsy (EUS-FNB) macroscopically, to detect whether it is sufficient or not. Aim of this study was to define the role of MOSE in judging the adequacy of the tissue core specimens and to evaluate its diagnostic yield and accuracy. Methods: This prospective study was conducted at our institution with 215 participants of both genders presenting for evaluation of solid or mixed solid and cystic lesions by MOSE technique by EUS-fine needle aspiration (FNA) or FNB. Results: In obtaining conclusive sample MOSE score 1 sensitivity was 68.2%, specificity was 75%, positive predictive value (PPV) was 99.3, negative predictive value (NPV) was 4.3 and overall accuracy was 68.4, in MOSE score 2 sensitivity was 88%, specificity was 75%, PPV was 99.5, NPV was 10 and overall accuracy was 87, in MOSE 2 (FNB) sensitivity was 92%, Specificity was 67%, PPV was 99.4, NPV was 12, 5 and overall accuracy was 92.There was no statistically significant difference between the two groups with conclusive and inconclusive cytopathological results regarding size of the needle, number of needle passes, type of the needle and the specimen acquisition method. Conclusion Using MOSE for assessment of adequacy of the sample obtained by EUS-FNB showed higher diagnostic yield compared to conventional method using different needle sizes.

Background: Endoscopic ultrasound (EUS) tissue acquisition requires rapid on-site evaluation to improve diagnostic yield with less needle passes;however, this is not readily available in all centers, also it increases the duration and the cost of the procedure. Macroscopic on-site evaluation (MOSE) is the direct assessment of the tissue sample provided by EUS-guided fine needle biopsy (EUS-FNB) macroscopically, to detect whether it is sufficient or not. Aim of this study was to define the role of MOSE in judging the adequacy of the tissue core specimens and to evaluate its diagnostic yield and accuracy. Methods: This prospective study was conducted at our institution with 215 participants of both genders presenting for evaluation of solid or mixed solid and cystic lesions by MOSE technique by EUS-fine needle aspiration (FNA) or FNB. Results: In obtaining conclusive sample MOSE score 1 sensitivity was 68.2%, specificity was 75%, positive predictive value (PPV) was 99.3, negative predictive value (NPV) was 4.3 and overall accuracy was 68.4, in MOSE score 2 sensitivity was 88%, specificity was 75%, PPV was 99.5, NPV was 10 and overall accuracy was 87, in MOSE 2 (FNB) sensitivity was 92%, Specificity was 67%, PPV was 99.4, NPV was 12, 5 and overall accuracy was 92.There was no statistically significant difference between the two groups with conclusive and inconclusive cytopathological results regarding size of the needle, number of needle passes, type of the needle and the specimen acquisition method. Conclusion Using MOSE for assessment of adequacy of the sample obtained by EUS-FNB showed higher diagnostic yield compared to conventional method using different needle sizes.

Background: Endoscopic ultrasound (EUS) tissue acquisition requires rapid on-site evaluation to improve diagnostic yield with less needle passes;however, this is not readily available in all centers, also it increases the duration and the cost of the procedure. Macroscopic on-site evaluation (MOSE) is the direct assessment of the tissue sample provided by EUS-guided fine needle biopsy (EUS-FNB) macroscopically, to detect whether it is sufficient or not. Aim of this study was to define the role of MOSE in judging the adequacy of the tissue core specimens and to evaluate its diagnostic yield and accuracy. Methods: This prospective study was conducted at our institution with 215 participants of both genders presenting for evaluation of solid or mixed solid and cystic lesions by MOSE technique by EUS-fine needle aspiration (FNA) or FNB. Results: In obtaining conclusive sample MOSE score 1 sensitivity was 68.2%, specificity was 75%, positive predictive value (PPV) was 99.3, negative predictive value (NPV) was 4.3 and overall accuracy was 68.4, in MOSE score 2 sensitivity was 88%, specificity was 75%, PPV was 99.5, NPV was 10 and overall accuracy was 87, in MOSE 2 (FNB) sensitivity was 92%, Specificity was 67%, PPV was 99.4, NPV was 12, 5 and overall accuracy was 92.There was no statistically significant difference between the two groups with conclusive and inconclusive cytopathological results regarding size of the needle, number of needle passes, type of the needle and the specimen acquisition method. Conclusion Using MOSE for assessment of adequacy of the sample obtained by EUS-FNB showed higher diagnostic yield compared to conventional method using different needle sizes.

BACKGROUND: Targeted therapy has revolutionized the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact. METHODS: Seventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed. RESULTS: Seventeen patients had blasts with the pattern of LPCs (CD34+CD38−CD58−), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+CD38−CD58− phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38−CD58− phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38− CD58− phenotype was an independent risk factor for overall survival. CONCLUSION: The presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.
Adult ; Diagnosis ; Flow Cytometry ; Humans ; Leukemia* ; Multipotent Stem Cells ; Multivariate Analysis ; Phenotype* ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis* ; Recurrence ; Risk Factors ; Stem Cells ; Treatment Outcome

Objective To investigate the effect of N

Objective To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods Rats were received intraperitoneal (i.p.) injection of malathion 150 mg/kg along with citric acid (200 or 400 mg/kg, orally), atropine (1 mg/kg, i.p.) or citric acid 200 mg/kg + atropine 1 mg/kg and euthanized 4 h later. Results Malathion resulted in increased lipid peroxidation (malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase (AChE) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase (iNOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS expression in brain and liver. Conclusions The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.