Di(2-ethylhexyl) adipate plasticizer triggers hepatic, brain, and cardiac injury in rats: Mitigating effect of Peganum harmala oil.

Di(2-ethylhexyl) adipate (DEHA) is a widely used plasticizer and prevalent environmental contaminant. In this study, DEHA concentrations in the milk, cheese, and butter samples wrapped with food-grade commercial polyethylene films and stored at 4 °C for 30 days were detected using gas chromatographic analysis. Also, the effects of exposure to a high dose of DEHA for a long duration on the liver, brain, and heart of Wistar rats were assessed. Besides, the possible beneficial effect of Peganum harmala oil (PGO), in relieving DEHA induced adverse effects was explored. For this purpose, four groups (8 rats/group) were orally given physiological saline, PGO (320 mg/kg bwt), DEHA (2000 mg/kg bwt), or PGO + DEHA for 60 days. The results revealed that the DEHA concentrations in the tested dairy products were ordered as follows: (butter > cheese > milk). Notably, the detected levels in butter were higher than the specific migration limit in foods. DEHA induced a significant increase in the serum levels of glucose, alanine transaminase, aspartate transaminase, acetylcholine esterase, creatine kinase-myocardium bound, malondialdehyde, tumor necrosis factor-α, and interleukin-1ß. But, significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia were evident following DEHA exposure. A significant reduction in the serum level of superoxide dismutase, reduced glutathione, and brain-derived neurotrophic factor was recorded. Besides, a significant downregulation in hepatic CYP2E1, brain glial fibrillary acidic protein, and cardiac troponin I gene expression was noticed. Moreover, DEHA exposure induced a significant decrease in Bcl-2 immunolabeling, but Caspase-3 immunoexpression was increased. On the contrary, PGO significantly recused DEHA injurious impacts. Therefore, PGO could represent a promising agent for preventing DEHA-induced hepatotoxicity, neurotoxicity, and cardiotoxicity.

Effect of Acid Suppression on Peripheral T-Lymphocyte Subsets and Immunohistochemical Esophageal Mucosal Changes in Patients With Gastroesophageal Reflux Disease.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common prevalent disease. We aimed to assess the dynamic changes in the peripheral T lymphocytes and lymphocytes infiltrating the esophageal mucosa after treatment with proton-pump inhibitor (PPI) in patients with GERD. PATIENTS AND METHODS: A total of 200 patients who presented with upper GIT symptoms were included in this prospective study. All patients were subjected to full history taking, clinical examination, and complete blood count. Upper endoscopy was performed to detect the grade of GERD, followed by 4 quadrant biopsies before and 1 month after acid suppressive drug therapy. Histopathologic and immunohistochemical examination were carried out for all biopsies. Flow cytometry analysis for the peripheral T lymphocytes and cytokine profile assay before therapy and after therapy were also carried out. RESULTS: In total, 200 patients comprising 132 male individuals (66%) and 68 female individuals (34%) with a mean age of 47.9±18.3 were included. The risk factors for development of GERD were smoking in 87 (43.5%), spicy food intake in 26 (13%), analgesics in 46 (23%), excessive tea and coffee in 35 (17.5%), and nondetected risk factors in 6 (3%). Endoscopic examination using Los Angeles grading system revealed that 102 patients (51%) were grade A, 57 patients (28.5%) were grade B, 38 patients (19%) were grade C, and 3 patients (1.5%) were grade D. No statistically significant differences could be detected in HGB levels and WBC, PLT, monocyte, granulocyte, and eosinophil counts before and after treatment with PPI. Histopathologic examination of esophageal biopsies showed significant posttreatment improvement in 132 cases (66%); however, 66 cases (33%) including the 2 cases (1%) of Barrett's esophagus showed nonsignificant pathologic improvement compared with the pretreatment picture. Immunohistochemical staining of esophageal biopsies with CD3 (T-cell marker) and CD20 (B-cell marker), before and 1 month after treatment, showed the presence of a very large number of infiltrating B cells in the esophageal mucosa (700±30/10 HPF) with large aggregations; in contrast, T-cell infiltration appeared less marked (570±23/10 HPF), and they formed smaller aggregates than those of B cells in pretreated patients, with P<0.01. However, 1 month after treatment with PPI, esophageal biopsies revealed a marked decrease in the number of both B (10±2/10 HPF) and T (290±12/HPF) cells in 66% of patients, with a P<0.01 in comparison with the pretherapy pattern. However, the remaining 33% of patients still showed a significantly high number of T cells (490±28/HPF), with a P <0.05 in comparison with the responder group that formed small aggregates with larger cell sizes, indicating their activation. Cytokine profiles before and after treatment revealed significant posttreatment reduction in their levels in the 132 cases with improvement in their clinical manifestations, and endoscopic and histopathologic findings, but there is no obvious change in the measured cytokine levels in 66 patients who simultaneously had no improvement in their endoscopic, histopathologic findings and mild improvement in their clinical manifestations. Moreover, significant posttreatment reduction of IL-8 and IL-1ß in the 98 (49%) patients with Los Angeles grading B, C, and D was observed. With regard to serum levels of IL-10 and IL-4, there were no statistically significant differences before and after treatment with PPI. Peripheral blood immunologic parameters revealed a statistically significant reduction of the total CD3 absolute count, T-helper lymphocyte (CD4/CD3) percentage, T-helper lymphocyte absolute count, and the percentage and absolute cytotoxic T-lymphocyte count (CD8/CD3) after treatment with PPI. Moreover, the same significant difference of peripheral blood lymphocytes was detected after exclusion of patients with Los Angeles grade A, which may be considered normal. CONCLUSIONS: Acid-induced T-cell-related cytokine production plays an important role in inflammation occurring in patients with GERD. Mucosal and peripheral inflammation reduces with PPI use.

Assessment of peripheral blood lymphocyte subsets in children with iron deficiency anemia.

BACKGROUND: Iron plays an important role in body defense and essential for normal immune system development where its deficiency may result in an inadequate immune response. We aimed to assess the lymphocyte subsets in childhood iron deficiency anemia (IDA) with their laboratory correlations. METHODS: Fifty IDA (< 18 years) and 25 age and sex-matched healthy children were enrolled and a complete history was obtained and clinical examination was performed. Complete blood count, serum iron, total iron binding capacity and serum ferritin, were performed. Flow cytometric determination of peripheral blood CD3+, CD4+, CD8+ T-lymphocytes and CD19+ B-lymphocytes and CD4/CD8 ratio were done. RESULTS: Patients had significantly lower hemoglobin, Serum iron, ferritin levels and higher lymphocytic count in patients compared with controls (p = 0.001, 0.03, 0.001, 0.001 respectively). CD3 count and percentage were significantly lower in IDA patients compared to controls (p = 0.007 and 0.005 respectively). There was a Significant reduction in the CD4 count, percentage and CD4/CD8 ratio in patients compared with controls (p = 0.001, 0.001 and 0.005 respectively) while there was no significant difference regarding CD8 count and percentage. No significant difference between the two studied groups regarding either CD19 count or percentage (p = 0.28 and 0.18 respectively) were found. CONCLUSIONS: IDA is associated with impaired cell-mediated immune response specifically T-cell mediated immunity.

Improving carboxymethyl cellulose edible coating using ZnO nanoparticles from irradiated Alternaria tenuissima.

In this paper, gamma-irradiation was successfully used to intensify the yield of Zinc oxide nanoparticles (ZnONPs) produced by the fungus Alternaria tenuissima as a sustainable and green process. The obtained data showed that 500 Gy of gamma-irradiation increased ZnONPs' yield to approximately four-fold. The synthesized ZnONPs were then exploited to develop active Carboxymethyl Cellulose films by casting method at two different concentration of ZnONPs 0.5% and 1.0%. The physicochemical, mechanical, antioxidant, and antimicrobial properties of the prepared films were evaluated. The incorporation of ZnONPs in the Carboxymethyl Cellulose films had significantly decreased solubility (from 78.31% to 66.04% and 59.72%), water vapor permeability (from 0.475 g m-2 to 0.093 g m-2 and 0.026 g m-2), and oxygen transfer rate (from 24.7 × 10-2 to 2.3 × 10-2 and 1.8 × 10-2) of the respective prepared films. Meanwhile, tensile strength (from 183.2 MPa to 203.34 MPa and 235.94 MPa), elongation (from 13.0% to 62.5% and 83.7%), and Yang's modulus (from 325.344 to 1410.0 and 1814.96 MPa) of these films were increased. Moreover, the antioxidant and antimicrobial activities against several human and plant pathogens the prepared of Carboxymethyl Cellulose-ZnONPs films were significantly increased. In conclusion, the prepared Carboxymethyl Cellulose-ZnONPs films showed enhanced activities in comparison with Carboxymethyl Cellulose film without NPs. With these advantages, the fabricated Carboxymethyl Cellulose-ZnONPs films in this study could be effectively utilized as protective edible coating films of food products.

Vitamin D levels in acne vulgaris patients treated with oral isotretinoin.

BACKGROUND/OBJECTIVES: Acne vulgaris is a common inflammatory skin disease. Vitamin D deficiency plays a role in many inflammatory skin diseases. It may play a role in pathogenesis of acne vulgaris. This study aimed to assess serum levels of 25 hydroxy vitamin D in patients with acne vulgaris before and after treatment with isotretinoin and its relation with acne vulgaris severity. METHODS: Ninety patients with acne vulgaris and 60 age-sex matched healthy subject as controls have been recruited in this study. Patients were treated with 0.75 mg/kg/d isotretinoin for 3 months. Serum level of 25 hydroxy vitamin D has been measured at baseline and after treatment. RESULTS: Serum levels of 25 hydroxy vitamin D were significantly higher in patients with acne vulgaris than healthy controls (P = .001). There was a significant inverse relation between level of 25 hydroxy vitamin D and severity of acne vulgaris before treatment (P = .001). Serum levels of 25 hydroxy vitamin D were significantly increased after isotretinoin treatment in patients with acne vulgaris (P = .001). CONCLUSION: This study concluded that vitamin D may play a potential role in pathogenesis of acne vulgaris or acne vulgaris may have a negative effect on vitamin D synthesis. Further studies are needed to confirm these potential relations.

Serum 25-hydroxyvitamin D and CD4+CD25(+high) FoxP3+ Regulatory T cell as Predictors of Severity of Bronchial Asthma in Children.

Bronchial asthma (BA) is one of the common chronic diseases of childhood. Vitamin D deficiency has been associated with BA. Suppressor regulatory T cells (Treg) are important for the induction, maintenance of immunological tolerance to allergens. This study assessed serum 25-hydroxyvitamin D (vitamin D) and the percentages of CD4+CD25+(high) Foxp3+ Treg, in peripheral blood, as predictors of asthma severity and level of clinical control. The study enrolled 72 children divided equally between asthmatic children (AC) and age and sex matched controls. Diagnostic criteria and level of asthma severity followed the Global Initiative for Asthma guidelines. Serum vitamin D was determined by an immunoassay and the percentages of CD4+CD25+ig Foxp3+ Treg by flow cytometry. Serum vitamin D level and percentage of CD4+CD25+(high) Treg were lower in AC compared to controls (P < 0.001) whereas Fox p3 expression was higher in AC compared to controls, P < 0.001. Serum vitamin D levels were lower in severe asthma compared to mild and moderate forms (P = 0.008) and in uncontrolled attacks compared to partially or completely controlled children. No difference in percentage of Treg in relation to asthma severity and clinical control was observed. Since AC has decreased serum vitamin D with inverse relationship between its levels and asthma severity, we conclude that it can be used to predict severity of asthma.

Assessment of serum 25-hydroxyvitamin d levels in children with atopic dermatitis: correlation with SCORAD index.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with an immunologic basis. It may have negative medical and social impacts on a patient and his family. OBJECTIVES: To assess serum level of vitamin D among children with AD and determine its association with AD severity using the AD Scoring System Index. STUDY DESIGN: A case-control study. PATIENTS AND METHODS: Twenty-nine patients with AD in the age group between 2 and 12 years were enrolled in the study. The severity of the disease was determined by the AD scoring system. Thirty controls were recruited. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] were tested using commercial automated chemiluminescent microparticle immunoassay. RESULTS: The mean value of vitamin D in children with AD was much lower than normal value, and there was a significant difference in the mean values of vitamin D between children with AD (5.4±1.9 ng/mL) and the controls (28.9±2.4 ng/mL). Serum 25(OH)D levels were found to be significantly higher in mild AD (14.6±3.5 ng/mL) compared with moderate (5.5±3.1 ng/mL) or severe AD (0.3±0.1 ng/mL); P<0.001. CONCLUSION: Patients with AD have lower serum vitamin D levels than normal. Vitamin D deficiency might be related to the severity of AD.