Immunomodulatory effects of Thymol through modulation of redox status and trace element content in experimental model of asthma.

Oxidative stress plays a key role in the immunopathogenesis of asthma. The objective of this study was to investigate the thymol effects on oxidative parameters along with trace elements in asthma experimental model. The Balb/c mice were sensitized by intraperitoneal injection of ovalbumin and thymol (8, 16 and 32 mg/kg) and dexamethasone (DEX) (2 mg/kg) were orally administered to sensitized mice. Oxidative stress parameters including protein carbonyl content, malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and total antioxidant capacity (TAC) besides trace element levels were evaluated. The protein carbonyl content, MDA and 8-OHdG in treated mice with 32 mg/kg of thymol significantly decreased compared to asthmatic mice (P < 0.01). Also, TAC significantly increased (P < 0.001) as well as zinc and selenium levels while copper level decreased. 16 mg/kg of thymol reduced the protein carbonyl content, MDA and 8-OHdG compared to asthmatic mice (P < 0.05). In addition, thymol improved the most prominent inflammation characteristics of asthma. The obtained results suggest that thymol has a protective effect against oxidative stress and it was also able to partially restore the defective trace element levels in asthma. Based on our observations, thymol may be used for alternative / complementary therapy in asthma.

A case of recurrent hematuria in primary prostatic low grade mucosa associated lymphoid tissue.

BACKGROUND: Primary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignancy. We found only 8 cases of MALT lymphoma in literature. CASE PRESENTATION: We report here another case of primary prostatic MALT lymphoma which is presented by hematuria and diagnosed primarily as BPH. Immunohistochemistry studies demonstrate the diagnosis and MALT lymphoma. Six months after starting the treatment the patient was alive and well. CONCLUSIONS: Prostatic MALTomas are mainly presented with urinary obstruction or hematuria and have an indolent growth with a good prognosis.

Adult Celiac Disease: Patients Are Shorter Compared with Their Peers in the General Population.

BACKGROUND Delay in diagnosis of celiac disease (CD) occurs frequently, although its consequences are mostly not known. One of the presented symptoms in pediatric patients with CD is the short stature. However, far too little attention has been paid to physical features including height of adult patients with CD. This study was undertaken to evaluate whether patients suffering from CD are shorter in comparison with the general population without CD. As well, we evaluated probable correlations between demographic and physical features, main complains, serum anti tTG level, and intestinal pathology damage between short (lower quartile) versus tall stature (upper quartile) patients with CD. METHODS This was a retrospective cross-sectional study on 219 adult patients diagnosed as having CD in the Celiac Disease Center, between June 2008 and June 2014 in Mashhad, Iran. The exclusion criteria were ages less than 18 and more than 60 years. Height was compared with a group of 657 age- and sex matched control cases from the healthy population. The probable influencing factors on height such as intestinal pathology, serum level of anti-tissue transglutaminase(anti-tTG), serum vitamin D, and hemoglobin level at the time of diagnosis were assessed and were compared in short (lower quartile) versus tall stature (upper quartile) patients with CD. RESULTS Both male (n=65) and female (n=154) patients with CD were shorter than their counterpart in the general population (males: 168.5±8.6 to 171.3±7.2cm, p <0.01 and females: 154.8±10.58 to 157.8±7.2 cm, p <0.01). Spearman linear correlation showed height in patient with CD was correlated with serum hemoglobin (p <0.001, r=0.285) and bone mineral density (p<0.001) and not with serum vitamin D levels (p =0.024, r=0.237), but was not correlated with anti-tTG serum levels (p=0.97). CD patients with upper and lower quartile of height in men and women had no significant difference in the anti-tTG level and degree of duodenal pathology(Marsh grade). Anemia as main complaint was more prevalent in shorter versus taller men. CONCLUSION Adults with CD are shorter compared with healthy adults. There is a direct correlation between height and anemia and bone mineral density. This finding highlights the importance of early detection and treatment of CD.

Correlation Between Cut-off Level of Tissue Transglutaminase Antibody and Marsh Classification.

BACKGROUND Duodenal biopsy is required for diagnosis of celiac disease in adults, although some studies have suggested adequate accuracy of serology alone. OBJECTIVE: We aimed to assess the correlation between anti-tissue transglutaminase (tTG) titer and pathological findings and to define the specific level of tTG for predicting celiac disease in adults without the need for biopsy sampling. METHODS This descriptive study was done on 299 participants. The tTG titer and pathological findings of duodenal biopsy samples were used for this study. Analysis of Receiver operating characteristic (ROC) curve was used to find a cut-off point of anti-tTG antibody for mucosal atrophy. RESULTS Mean tTG titers was significantly higher in patients graded as Marsh III≥ 3 (p=0.023). ROC curve analysis showed 89.1% sensitivity for cut-off point≥76.5 IU/mL of anti-tTG. For Marsh≥ II, specificity was 28% and positive predictive value was 91%.CON CLUSION There is a linear correlation between increasing tTG level and Marsh I to III. Specificity of tTG titer more than 200 was 100% for Marsh >2.

Microscopic enteritis: Bucharest consensus.

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

Primitive neuroectodermal tumor with kidney involvement: a case report.

Primitive neuroectodermal tumor (PNET) is usually an aggressive, rapidly progressing and metastasizing tumor. Occurrence of this type of tumor in the kidney is considered as unusual and few cases have been reported so far. We present a metastatic PNET arising probably from the kidney in a 17-year-old female patient with local invasion and metastasis to the stomach. PNET should be considered as a differential diagnosis of a large heterogeneous soft tissue mass in the abdomen, especially in those with widely local invasion and metastases.

Congenital sacral mesenchymal chondrosarcoma in a neonate: a case report and review of literature.

Mesenchymal chondrosarcomas are rare malignant tumours in children, especially, in neonates. The authors present a case of congenital mesenchymal chondrosarcoma in a 1-day neonate located in sacrum. According to the authors' literature searches, this case is the first congenital sacral mesenchymal chondrosarcoma. We also reviewed the papers published in English literatures.

Diagnostic Value of ASCA and Atypical p-ANCA in Differential Diagnosis of Inflammatory Bowel Disease.

BACKGROUND: Worldwide, the incidence of inflammatory bowel disease (IBD) is increasing. This study aims to evaluate the diagnostic value of two serological markers, atypical perinuclear anti-neutrophil cytoplasmic antibodies (atypical-P-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA), with the intent to determinetheir relationship to ulcerative colitis (UC) and Crohn's disease (CD), in addition to the location and extent of bowel involvement. METHODS: There were 97 patients enrolled in this study, 72 diagnosed with UC and 25 with CD.The control group consisted of 40 healthy individuals. ASCA was determined by enzyme-linked immunosorbent assay (ELISA) and atypical-P-ANCA by indirect immunofluorescence assay (IIF). For data analyses, we used the chi-square and independent t-tests. Significance was considered to be p<0.05. RESULTS: For CD, the sensitivityof ASCA was 16% and its specificity was 97%.ASCA had a specifity of 90% in UC patients. The atypical P-ANCA test had a sensitivity of 44% and specificity of 86% for UC. The positive predictive value (PPV) for atypical P-ANCA in UC patients was 78% and for the negative predictive value (NPV), it was 58%.There was no correlation between ASCA and atypical P-ANCA results and the location of gastrointestinal (GI) involvement in CD (p=0.61) and UC (p=0.28) patients. CONCLUSION: According to the results, ASCA and atypical P-ANCA markers are not useful for IBD screening. Our study suggests that atypical P-ANCA is a useful parameter to differentiate UC from CD. However, ASCA is of limited value for screening and differentiating UC from CD.

Postoperative histological changes in polypose rhinosinusitis.

The aim of this study was to evaluate the effect of surgery on the histology of nasal mucosa in patients with nasal polyposis and the comparison/also to compare it with normal population. This case-control study was conducted on 20 patients at the Otorhinolaryngology-Head and Neck Surgery Department, Qaem Hospital, Mashhad University of Medical Sciences during October 2007 to June 2008. Patients with polyposis and patients with septal deviation who were candidate for septoplasty were considered as case and control groups, respectively, including 10 subjects in each. Specimens of polyp tissue and the inferior conchae (mucosa) were taken during sinus endoscopy from the case group. One month later, another specimen was taken from the inferior conchae (mucosa). Moreover, specimens of the inferior conchae (mucosa) were taken of the control group. Percentage of goblet cells among the epithelial cells was determined for each group. Goblet cell percentage found to be 15.7% in polyps, consistent with significant difference with that of in postoperative (13.3%) and in preoperative nasal mucosa specimens (39.86%), (P = 0.043 and P = 0.03, respectively). Goblet cell percentage was 39.86% and 4.9% in the case and control groups, in that order, which were significantly high (P < 0.001). Percentage of goblet cells showed to be lower in polyps than mucosa. Also percentage of goblet cells in postoperative nasal mucosa specimens was significantly lower than preoperative specimens. Therefore, surgery has additional benefit of histological improvement rather than opening nasal airway.

Preventive Effect of Novel Bacterial Polysaccharide and Animal Splenic Protein as Natural Adjuvants on Animal Model of Asthma.

OBJECTIVES: Two new adjuvants from natural animal lipids (G2) and bacterial polysaccharide extracts (PC) were previously prepared by our group and showed a reduction in tracheal responsiveness. The aim of this study was to evaluate the preventive effect of recently introduced natural products (G2 and PC) on the development of asthma. MATERIALS AND METHODS: Asthma was induced using a standard method in four groups of BALB/c mice. A non-sensitized control group was also included in order to be compared with treated groups. Three groups were premedicated with novel agents named G2, PC, and a combination of these two for 20 days before starting the induction of asthma. Bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells. Interferon-γ, and IL-4 and the histopathological of both lungs were also evaluated. RESULTS: In all pretreated groups, the inflammatory cells infiltration especially eosinophils and smooth muscle hyperplasia decreased significantly. BALF cytology also showed significant decrease in eosinophil count in all pretreated groups. There was a significant increase in the BALF and serum INF-γ in all pretreated groups but the combination of G2/PC was more effective. BALF IL-4 decreased significantly in the group pretreated with a combination of G2 and G2/PC (4.11±0.86 and 4.02±0.52 pg/ml in G2 and G2/PC, respectively). Serum IL-4 in the PC group was significantly higher than the sensitized control. CONCLUSION: G2 and PC may effectively prevent asthma development by activation of the type 1 T helper system.

Primary gastrointestinal lymphoma.

BACKGROUND: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. MATERIALS AND METHODS: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. RESULTS: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. CONCLUSION: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma.

Correlation between HBsAg quantitative assay results and HBV DNA levels in chronic HBV.

BACKGROUND: Viral load has been used to diagnose and monitor patients who are being treated for chronic hepatitis B (CHB). The Diagnosis methods are molecular-based and expensive. Quantitation of hepatitis B surface antigen (HBsAg) by automated chemiluminescent micro-particle immunoassay has been proposed to be a surrogate marker. Quantitating HBV DNA levels molecularly is expensive; thus, a cheaper laboratory test as a surrogate diagnostic marker might simplify our management. OBJECTIVES: We determined whether quantitative HBsAg levels correlate with HBV DNA levels in CHB. PATIENTS AND METHODS: In this cross-sectional study, all CHB patients who were referred by a gastroenterologist to undergo quantitative HBV DNA assay in a qualified laboratory in Mashhad, Iran in 2009 were enrolled, and blood samples was obtained. Patients who were positive for antibodies to HCV and HDV were excluded. HBV DNA was measured by real-time polymerase chain reaction, and serum HBsAg was quantified byelectrochemiluminescence assay (Roche Diagnostic). RESULTS: Of 97 patients, 70 were male (72%) and 27 were female (28%); the mean age was 39 ± 11 years. Eighty-seven percent wasHBeAg-negative. By Mann-Whitney test,HBSAg titer differed significantly between HBeAg-positive and -negative patients (P = 0.001), as did HBV DNA levels (P = 0.009). By Spearman test, there was no significant correlation between HBsAg and HBV DNA levels (P= 0.606 and r = 0.53). CONCLUSIONS: HBeAg-negative patients have higher levels of HBsAg and lower levels of HBV DNA. By electrochemiluminescence assay,HBsAg has no significant correlation with HBV DNA levels in CHB with predominant genotype D and HBeAg negativity in Iran.

Clinical relevance of HER-2/neu overexpression in patients with testicular nonseminomatous germ cell tumor.

INTRODUCTION: Recent scientific attention has focused on the role of growth factors in the progression of cancer. HER-2/neu is an epidermal growth factor receptor that is demonstrated to have correlation with poor prognosis of many cancers. This study evaluated the overexpression of HER-2/neu protein and its clinical importance in nonseminomatous germ cell tumors of the testis. MATERIALS AND METHODS: Testis specimens of 54 patients with testicular nonseminomatous germ cell tumors, referred to Omid Hospital from 2001 to 2007, were re-evaluated and the patients' records were reviewed. Patients' age, tumor subtype, tumor stage, tumor markers, therapeutic response, and disease-free survival were assessed and the specimens were evaluated for the degree of HER-2/neu expression using an immunohistochemistry method. RESULTS: Immunohistochemical staining was performed for 54 specimens. Overexpression of HER-2/neu was seen in 33.3% of the patients with nonseminomatous germ cell tumors, especially in those with teratocarcinoma subtype compared to those with mixed germ cell tumors or embryonal cell carcinoma. However, HER-2/neu overexpression did not show any correlation with tumor stage, therapeutic response, disease-free survival, age, beta-human chorionic gonadotropin, or alpha-fetoprotein. CONCLUSION: We observed overexpression of HER-2/neu receptor in teratocarcinoma subtype of germ cell tumor. We suggest further studies to evaluate the clinical importance of this finding.

Clinicopathological significance of E-cadherin, ß-catenin and p53 expression in gastric adenocarinoma.

BACKGROUND: E-cadherin/catenin complexes exert a role in cell adhesion. ß-catenin is a key player in Wnt signaling pathway in gastric cancer. P53 is a tumor suppressor gene which also regulates apoptosis. We assessed the expression of E-cadherin, ß-catenin and p53 in gastric adenocarcinoma, and their correlations with clinicopathological features. METHODS: Fifty six formalin-fixed, paraffin-embedded archival specimens of gastric adenocarcinoma were randomly included as cases. Adjacent tumor-free gastric mucosa of different premalignant stages was obtained from the cases. Immunohistochemical staining was performed to assess E-cadherin, ß-catenin and p53 expression. RESULTS: All chronic atrophic gastritis and intestinal metaplasia revealed normal membranous staining. Only one patient with dysplasia had abnormal expression of E-cadherin and ß-Catenin. Abnormal E-cadherin, ß-catenin and p53 expression was found in 50%, 48.2% and 76.8% of cancer specimens respectively. Abnormal expression of E-cadherin was significantly correlated with aberrant ß-catenin expression. Abnormal E-cadherin and ß-catenin expression were significantly correlated with depth of tumor invasion and advanced gastric cancer (p < 0.05), lower degree of differentiation and diffused tumor type (p < 0.001). Node metastasis was not influenced by abnormal expression of E-cadherin and ß-catenin. P53 was not associated with clinicopathological variables. CONCLUSIONS: Abnormal expression of the E-cadherin and ß-catenin were associated with each other and influenced by histogenesis of gastric cancer and malignant behavior of tumor but not significant in premalignant lesions. They are more frequent in diffuse type and associated with advanced gastric cancer. P53 alterations are more frequent in the Iranian population compared with others.

p16 promoter hypermethylation: a useful serum marker for early detection of gastric cancer.

AIM: To determine p16 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features. METHODS: Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction (MSP) was used to evaluate methylation status of p16 promoter. p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections. RESULTS: Methylation was detected in 44.2% (23/52) of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients (14/52). Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases (32/52), and was significantly associated with promoter hypermethylation (P < 0.001). Methylation was significantly more frequent in higher pathological grades (P < 0.05). Methylation was not associated with other clinicopathological features and environmental factors including H pylori infection and smoking. CONCLUSION: p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.

Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features.

BACKGROUND: The p53 gene mutation is closely related to carcinogenesis in most malignant diseases. The main function of wild p53 protein is to maintain the integrity of genes by detecting mutations and preventing the division of cells with damaged DNA. The mutated form of p53 protein is overexpressed due to an extended half-life and can be easily detected by immunohistochemistry. OBJECTIVE: To estimate the frequency of p53 protein overexpression in colorectal carcinoma and its correlation with some clinicopathologic variables. METHODS: One hundred paraffin-preserved colorectal carcinoma samples were collected randomly from patients undergoing tumor resection from April 1995 through April 2001 in Omid Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The overexpression of p53 protein was studied using a monoclonal antibody (clone DO-7; Dako). The number of cells stained were classified semiquantitatively as (-): <5% positive cells, (+): 5 - 25% positive cells, (++): 25 - 75% positive cells, and (+++): >75% positive cells. Clinicopathologic data including gender, age, tumor location, histologic type, and stage (Astler-Coller) were collected from the files maintained at the Department of Pathology. The correlation between p53 protein overexpression and each variable was evaluated using Chi-square analysis. RESULTS: p53 staining was positive in 59 of 100 specimens. Out of these 100 specimens, 16 were weekly (+), 16 moderately (++), and 27 intensely (+++) positive for p53 protein over-expression. There was no significant correlation between p53 staining and gender (P = 0.34), age (< 40 vs. > or = 40 yr; P = 0.74), site of tumor (right vs. left colon and rectum; P = 0.26), pathologic type (mucinous vs. nonmucinous; P = 0.63), and stage of the disease (P = 0.12). CONCLUSION: Considering the p53 protein overexpression in a relatively high percentage of patients, it seems that p53 mutation plays an important role in development of colorectal carcinoma. There was no significant association between p53 protein expression and some common clinicopathologic variables such as age, gender, site of tumor, pathologic type, and stage of the disease.

Evaluation of the relationship between human epidermal growth factor receptor-2/neu (c-erbB-2) amplification and pathologic grading in patients with breast cancer.

OBJECTIVE: The human epidermal growth factor receptor-2 (HER-2)/neu is a proto-oncogene that is amplified in 10-30% of breast cancers. It is known to be associated with a poor overall survival. We studied the relationship between its amplification and different histological gradings of breast cancer. METHODS: We studied 196 patients diagnosed with breast cancer in 2005 at the Omid and Ghaem Training Hospital, Mashhad Medical University, Iran. The HER-2/neu oncoprotein was measured by immunohistochemistry and the histological gradings were carried out according to the Bloom-Richardson Grading system. RESULTS: Sixty-seven (34.2%) cases were HER-2/neu positive and 129 (65.8%) cases were HER-2/neu negative. Overexpression of HER-2/neu was significantly higher in breast cancer patients <30 years (50% versus 33.3%, p=0.034). There was a non-significant statistical relationship between histological grading and overexpression of HER-2/neu oncogen (p=0.087). Twelve (17.5%) of HER-2/neu positive cases were metastatic and only 4 (3.1%) of HER-2/neu negative cases had metastasis (p=0.051). CONCLUSION: HER-2/neu gene amplification or its overexpression is detected in approximately 34.2% of breast cancer cases. Patients with HER-2/neu positive breast cancer have higher stage and grade diseases. This may help to use a better treatment for patients.

Aberrant p16 methylation, a possible epigenetic risk factor in familial esophageal squamous cell carcinoma.

AIM: Detection of methylation in the p16 gene, an inhibitor of cyclin D-dependent protein kinase, as a new tumor marker for early detection of esophageal squamous cell carcinoma (ESCC) in DNA derived from blood and serum. METHOD: A large family with clustering of ESCC was assessed in Khorasan province in northeastern Iran. The family had three histologically proven cases of ESCC in two consecutive generations and several other deceased cases with histories of ESCC. DNA from blood of 28 living family members in three consecutive generations, 30 sporadic ESCC cases (from serum, blood, and tumor tissues), and 30 healthy volunteers (from blood) were examined for the methylation status of p16 promoter using methylation-specific PCR (MSP). RESULTS: Aberrant p16 promoter methylation was found in 64.3% (n = 28) of ESCC family members and none (n = 30) of our normal volunteers. Five of the 28 family members with esophageal cancer symptoms had negative endoscopy results for ESCC, while four of these members had p16 hypermethylation in their blood. The family members with negative endoscopy and positive p16 promoter methylation are being monitored closely for signs of ESCC development through regular check-ups and chromoendoscopies. In sporadic ESCC in northeastern Iran, 73.3% (n = 30) of tumor tissue samples had p16 hypermethylation. Serum and blood samples from the same patients showed p16 hypermethylation in 26.6% and 43.3% of the samples, respectively. CONCLUSION: Aberrant p16 methylation may be a valuable diagnostic tool as a tumor marker for the early identification of individuals in high risk ESCC families.