Evaluation of phenotypic and genotypic characteristics of carbapnemases-producing enterobacteriaceae and its prevalence in a referral hospital in Tehran city

Background & Objective: Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide including Iran. The emergence of this pathogen is worrying as carbapenem is one of the �last-line� antibiotics for treatment of infections caused by multi drug resistant gram- negative bacteria. The main objective of this study was to determine the prevalence of carbapenem-resistant Enterobacteriaceae in a referral hospital in Tehran, Iran. Methods: In this study, all positive isolates of Enterobacteriaceae recorded in blood, urine, and other body fluids were studied during April 2017 to April 2018 in a referral hospital in Tehran. All cases of resistance to carbapenems were first tested by modified Hodge test. All cases with positive or negative test, after gene extraction, were examined genotypically based on the primers designed for the three Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and OXA-48 genes by conventional PCR method. Results: 108 isolates (13.6) were resistant to all cephalosporins as well as to imipenem and meropenem. In a genotypic study, including 45 isolates, 13 isolates were positive for OXA-48 gene, 11 isolates for OXA-48 and NDM genes, 11 isolates for OXA-48, NDM and KPC genes, 4 isolates for OXA-48 genes and KPC, 3 isolates for NDM, one isolate for KPC. On the other hand, two isolates were negative for all three genes examined. Conclusion: OXA-48 gene was one of the most common genes resistant to carbapenems in Iran. According to studies, the prevalence of antibiotic resistance in Iran is rising dramatically, which reduces the choice of antibiotics to treat severe infections in the future. © 2020, Iranian Society of Pathology. All rights reserved

Frequency of CD4+ and CD8+ T cells in Iranian chronic rhinosinusitis patients

Background: Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4+ and CD8+ T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells. Methods: In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4+, CD8+, and CD68+ cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10 of total inflammatory cells. The Kruskal-Wallis, Mann-Whitney, and Spearman tests were used in statistical analyses. Results: The median (range) age of the studied groups was: 32 (14-67) for CRSwNP, 28 (10-43) for CRSsNP, and 27 (17-44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neutrophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4+ and CD8+ T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls. Conclusion: The frequency of CD4+ and CD8+ T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed. © 2018 The Author(s)

Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients

Background: Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. Methods: Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. Results: We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-β was significantly elevated in the sinonasal tissue of patients with CRSsNP. Conclusions: Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.Figure not available: see fulltext. © 2020 The Author(s)

The local and circulating SOX9 as a potential biomarker for the diagnosis of primary bone cancer

Purpose: The status of the local and circulating SOX9, a master regulator of the tumor fate, and its relevance to tumor types, severity, invasion feature, response to therapy, and chemotherapy treatment were surveyed in bone cancer in the current study. Methods: The SOX9 expression level was evaluated in tissue and peripheral blood mononuclear cells from patients with different types of malignant and benign bone tumors also tumor margin tissues using Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry and western blot analysis. Also, the correlations of the SOX9 expression level with the patient's clinical and pathological features were considered. Results: The remarkable overexpression of SOX9 was detected in bone tumors compared to tumor margin tissues (P < 0.0001). Malignant bone tumors revealed a higher expression of SOX9 compared to benign tumors (P < 0.0001) while osteosarcoma tumors showed higher expression levels compared to Ewing sarcoma, and chondrosarcoma. Overexpression of SOX9 was observed in high grade, metastatic, recurrent tumors also tumors with poor response to therapy. Besides, the patients under the chemotherapy treatment demonstrated higher levels of SOX9 compared to the rest of malignant tumors (P = 0.02). The simultaneous up-regulation of circulating SOX9 in the patients with bone cancer was observed compared to healthy individuals (P < 0.0001) accompanying with overexpression of SOX9 in malignant tumors compared to benign tumors (P < 0.0001). The circulating SOX9 expression was up-regulated in the patients with malignant bone tumors who receive chemotherapy treatment also patients with high grade, metastatic, recurrent tumors. The protein level of SOX9 was in line with our data on the SOX9 gene expression. Conclusion: The simultaneous overexpression of local and circulating SOX9 in bone cancer besides its positive correlation with tumor severity, malignancy, size, and chemotherapy may deserve receiving more attention in bone cancer diagnosis and therapy. © 2020 The Author

Are osteopontin and Ki67 expressions different in various histologic grades of meningioma? An iranian experience

Background: Meningioma is among the most common slow growing central nervous neoplasms, which recurs locally despite the benign histologic features. The aim of this study was to evaluate osteopontin and ki67 expressions in different histologic grades of meningioma in a group of Iranian people. Methods: In this cross-sectional study, first, the paraffin blocks with the definite pathological diagnosis of meningioma in 70 patients were cut by microtome, in 4-5 micron sizes and stained for immunohistochemical markers of osteopontin and ki67. Then, all samples were evaluated for positive immunoreactivity and contributing factors. Results: Among 70 pateints studied, the mean for the Ki67 level was 8.6±12.3 and the mean for the osteopontinm IHC score was 45.2±77.9. There was a high correlation between markers, tumor recurrence and grade (P<0.001). In addition, there was a significant direct correlation between ki67 and osteopontin levels (P<0.001, r=0.760). In other words, as OPN and ki67 expressions increased, the chance of tumor recurrence increased. Conclusion: ki67 and osteopontin expressions in patients with meningioma can be used as good prognostic markers for tumor recurrence and for distinguishing the grade of meningiomas. © Iran J Pathol. All rights reserved

Right ventricular myxoma originating from a papillary muscle: a case report

Very few cases of ventricular myxoma originate from a papillary muscle. Patients with a cardiac myxoma and a history of colorectal carcinoma are also rare. Here, we present a case of an extremely large right ventricular myxoma that originated from the posteromedial papillary muscle in a patient with a history of colorectal carcinoma. © 2016, Wiley Periodicals, Inc

Validation of oxford classification of immunoglobulin a nephropathy: An Iranian experience

Introduction. In 2009, the Oxford classification of immunoglobulin A (IgA) nephropathy was proposed by the working group of the International IgA Nephropathy Network and Renal Pathology Society. It established specific pathologic features that predict the risk of progression of disease. This study aimed to evaluate the interobserver reproducibility of the Oxford classification of IgA nephropathy between Iranian nephropathologists. Materials and Methods. We included 100 patients with primary IgA nephropathy diagnosed between 2001 and 2011. Histologic slides were circulated among 4 pathologists. A score sheet was answered by each individual pathologist for each biopsy, according to the instruction of the Oxford classification. Reproducibility was determined for each variable, using intraclass correlation coefficient (ICC). Results. The ICC values calculated for each major category of the Oxford classification were as follows: the highest score of 0.94 for tubular atrophy and interstitial fibrosis; 0.8 for glomerular basement membrane duplication, extracapillary proliferation, and segmental endocapillary proliferation; and 0.1 to 0.3 for arterial lesions, especially for hyalinosis of arterioles and intimal thickening of arcuate vessels and interlobar arteries. Conclusions. The Oxford classification of IgA nephropathy is a useful tool and evidenced-based method with high interobserver reproducibility in pathology reporting. Our data suggest that Oxford classification may be used as a model for classification of other renal pathologies in the future. © 2016, Iranian Society of Nephrology. All Rights Reserved

Significant effect of simvastatin and/or ezetimibe-loaded nanofibers on the healing of femoral defect: An experimental study

Background: Fracture healing complications are associated with significant healthcare and economic burden. In this study, we aimed to investigate how the combined administration of local simvastatin and ezetimibe into the femoral defect of the animal model affects the bone-healing process in comparison with their monotherapy. Methods: A total of 32 four-month-old adult male Wistar rats were randomized into the four study groups: simvastatin + ezetimibe-loaded nanofibers (group 1), simvastatin-loaded nanofibers (group 2), ezetimibe-loaded nanofibers (group 3), and non-loaded nanofibers (group 4). After the generation of femoral defects, the predesigned nanofibers were locally administered into the defect site. The healing measures were serum and bone osteoprotegerin (OPG) expression, pathologic evaluation of union (Allen's fracture healing scores), and radiographic evaluation of bone density (Hounsfield scale) at weeks 2 and 4. Results: The improvement of all evaluated healing measures was remarkably superior in rats that were treated with loaded nanofibers in comparison with the control group. Also, the improvement of all evaluated healing measures was considerably more in the simvastatin-ezetimibe combination therapy group compared to their monotherapy. All the evaluated measures were superior in the ezetimibe monotherapy group compared to the simvastatin monotherapy group. Conclusion: The cumulative effect of simvastatin and ezetimibe on the induction of bone healing is more significant than the individual effect of these drugs. Therefore, local administration of nanofibers loaded with simvastatin and ezetimibe could be regarded as a promising osteoinductive compound for the acceleration of bone repair. © 202

Immunomodulatory effects of vitamin D3 on gene expression of MDGF, EGF and PDGFB in endometriosis

Research question: Endometriosis, an inflammatory disease, is assumed to be associated with an increased production of growth-related cytokines. Based on the emerging immunomodulatory role of vitamin D3 in different inflammatory conditions, this study aimed to examine its modulatory effect on the expression levels of the genes for platelet-derived growth factor-B (PDGFB), monocyte/macrophage-derived growth factor (MDGF, also known as PPBP) and epidermal growth factor (EGF) in peritoneal fluid mononuclear cells (PFMC) in women with and without endometriosis. Design: PFMC from 10 women with endometriosis and 10 control participants were treated with vitamin D3.The gene expression levels of PDGFB, MDGF and EGF were measured 6, 24 and 48 h following vitamin D3 administration using real-time PCR. Results: Gene expression levels of EGF and PDGFB were higher in the PFMC of women with endometriosis than the control group (P = 0.006, P < 0.001, respectively). Although MDGF expression showed an increase in the endometriosis group compared with non-endometriotic controls, no significant difference was found. Vitamin D3 significantly decreased EGF expression at 6, 24 and 48 h (P < 0.001, P < 0.001 and P = 0.007, respectively), MDGF at 24 and 48 h (P < 0.001 and P = 0.009, respectively) and PDGFB at 6 h (P = 0.047) in the endometriosis group. Vitamin D3 treatment had no significant effect on expression of the genes in the PFMC of non-endometriotic women. Conclusions: The study concluded that PDGFB and EGF gene expression increases in endometriosis, and vitamin D3 could markedly decrease this expression, suggesting its therapeutic potential in endometriosis. © 2020 Reproductive Healthcare Ltd

Validation of oxford classification of immunoglobulin a nephropathy: An Iranian experience

Introduction. In 2009, the Oxford classification of immunoglobulin A (IgA) nephropathy was proposed by the working group of the International IgA Nephropathy Network and Renal Pathology Society. It established specific pathologic features that predict the risk of progression of disease. This study aimed to evaluate the interobserver reproducibility of the Oxford classification of IgA nephropathy between Iranian nephropathologists. Materials and Methods. We included 100 patients with primary IgA nephropathy diagnosed between 2001 and 2011. Histologic slides were circulated among 4 pathologists. A score sheet was answered by each individual pathologist for each biopsy, according to the instruction of the Oxford classification. Reproducibility was determined for each variable, using intraclass correlation coefficient (ICC). Results. The ICC values calculated for each major category of the Oxford classification were as follows: the highest score of 0.94 for tubular atrophy and interstitial fibrosis; 0.8 for glomerular basement membrane duplication, extracapillary proliferation, and segmental endocapillary proliferation; and 0.1 to 0.3 for arterial lesions, especially for hyalinosis of arterioles and intimal thickening of arcuate vessels and interlobar arteries. Conclusions. The Oxford classification of IgA nephropathy is a useful tool and evidenced-based method with high interobserver reproducibility in pathology reporting. Our data suggest that Oxford classification may be used as a model for classification of other renal pathologies in the future. © 2016, Iranian Society of Nephrology. All Rights Reserved