Immunological role of CD4<Superscript>+</Superscript>CD28<Superscript>null</Superscript> T lymphocytes,natural killer cells,and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4⁺CD28^null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4⁺CD28^null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4⁺CD28^null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4⁺CD28^null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4⁺CD28^null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4⁺CD28^null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4⁺CD28^null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.     

Effect of Topical Application of Black Seed Oil on Imiquimod‐Induced Psoriasis‐like Lesions in the Thin Skin of Adult Male Albino Rats

Psoriasis is a chronic inflammatory skin disease that affects about 1%–3% of the world's population. Black seed oil, i.e., the oil extracted from black seeds (Nigella sativa seeds), possesses a broad spectrum of pharmacological actions including anti‐inflammatory, immunostimulatory, and antioxidant properties. This study aimed to investigate the effect of black seed oil on imiquimod (IMQ) induced psoriasis‐like skin lesions. To this end, 30 male albino rats were divided into three groups: group I, control group; group II, psoriasis‐induced group receiving daily topical applications of IMQ cream (5%) on the shaved back skin for 10 consecutive days; and group III, black seed oil group receiving a daily topical dose of black seed oil 5 mg/kg body weight for 10 days after induction of psoriasis. Animals of all groups were sacrificed and specimens obtained from the skin of the central part of the back were processed for histological and immunohistochemical staining with proliferating cell nuclear antigen (PCNA). IMQ application led to epidermal inflammation, hyperplasia and alterations in the normal appearance of keratinocytes with degenerative changes observed at both light and electron microscopic levels. Collagenous fibers were abundant in the dermis and PCNA‐positive cells were detected in all layers of the epidermis. However, topical use of black seed oil strongly inhibited IMQ‐induced psoriasis‐like inflammation and alleviated all epidermal and dermal changes observed after IMQ application, allowing us to conclude that black seed oil can be used as an adjuvant topical therapy for treating psoriasis. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:166–174, 2018. © 2017 Wiley Periodicals, Inc.     

Misoprostol decreases oxidative stress and liver injury in bacterial lipopolysaccharide-induced endotoxemia in mice

The effect of misoprostol, a synthetic prostaglandin E1 analog, on the development of oxidative stress induced in mice with lipopolysaccharide (LPS) endotoxin was investigated. Misoprostol was administered by intraperitoneal route (i.p.) at doses of 10, 100, or 1,000 μg/kg at the time of LPS injection (200 μg/kg, i.p.). Mice were euthanized 4 h later. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels as well as paraoxonase activity were measured in brain and liver. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as DNA fragmentation were determined in the liver. The administration of LPS increased oxidative stress both in the brain and liver tissue. There were significantly increased MDA and nitrite and decreased GSH and PON1 activity in the brain and liver, respectively. In addition, LPS was associated with markedly elevated plasma ALT and AST level as well as increased liver DNA fragmentation. The administration of misoprostol at 100 or 1,000 μg/kg decreased brain MDA by 17.6 and 30 %, increased GSH by 29.8 and 33.3 %, and decreased nitric oxide by 21.74 and 42.5 %, respectively, compared with the lipopolysaccharide control group. Liver MDA decreased by 27 %, GSH increased by 47.7 %, and nitric oxide decreased by 37.2 % with misoprostol at 1,000 μg/kg. Paraoxonase activity increased in both the brain and liver by misoprostol administration. The increase in liver AST and ALT and DNA fragmentation after endotoxin administration was normalized by misoprostol. These results indicate that misoprostol can alleviate oxidative stress in the presence of a mild systemic inflammatory illness, indicating a new and potentially important therapeutic application for the drug.     

Teleaudiology practice in COVID-19 pandemic in Egypt and Saudi Arabia

Objective:To evaluate the audiologists’attitudes and practice towards teleaudiology, as well as to assess the audiological services provided in Egypt and Saudi ...     

Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological,Immunohistochemical, and Biochemical Study

Potassium bromate (KBrO₃) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO₃ mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO₃ induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO₃ orally twice weekly for 4 weeks and Group 4: received both KBrO₃ and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO₃ induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO₃. Anat Rec, 299:1256–1269, 2016. © 2016 Wiley Periodicals, Inc.     

Analysis of UV-induced damage and repair in young and senescent human dermal fibroblasts using the comet assay

A major cause of ageing is thought to be the accumulation of damage to macromolecules. Accumulation to DNA damage in cells therefore presupposes that aged cells are unable to repair this damage. We have used the in vitro model of cellular ageing to test the idea that senescent cells are deficient in some aspect of DNA repair. Using the alkaline single cell gel electrophoresis assay (comet assay), we have determined the responses of young and senescent human dermal fibroblasts to DNA damage caused by exposure to UVC light. At low doses of UVC, senescent cells generate smaller comets than young cells whilst at medium doses the situation is reversed. At high doses, young and senescent cells respond similarly to one another. Time course experiments revealing repair of DNA damage show that senescent cells generate larger comets than young cells at early stages of repair suggesting that either senescent cells bear more damage per genome than do young cells or that senescent cells are more efficient at excising bulky adducts from DNA. Cells maintained in low levels of serum irrespective of age are less able to repair DNA damage compared with cells maintained in high levels of serum, and furthermore young and senescent cells maintained in high levels of serum are equally able to repair DNA damage. Our data, therefore, reveal both age-dependent and age-independent responses to UV-induced DNA damage. Use of the comet assay highlights the heterogeneity of cellular responses to genotoxic stress.     

Effect of Alginate Microbead Encapsulation of Placental Mesenchymal Stem Cells on Their Immunomodulatory Function

In this research we have used different cytokines and progesterone to enhance the immunomodulatory capacity of placental-derived stem cells (PLSCs) prior to their encapsulation. We assessed the effect of microencapsulation of the cells without (control) or after 3-day treatment with interferon gamma (INFγ), interleukin10 (IL-10), or progesterone (P4). Treated PLSCs demonstrated strong immunosuppressive effects on phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMNCs). INFγ treatment resulted in the strongest immune inhibition among the treated groups. The treatments enhanced soluble human leukocyte antigen (sHLAG) secretion compared to control. The IL-10-treated group showed the highest effect on HLAG secretion compared to other groups. Alginate encapsulation of PLSCs did not affect cell viability, or sHLAG secretion. Also, after treatment the encapsulated PLSCs inhibited PHA-activated PBMNCs in the same manner as unencapsulated cells. We studied two groups of encapsulated PLSCs, one without perm-selective poly-l-ornithine (PLO)-coating and the other with PLO-coating, and measured levels of sHLAG secreted. We found no difference in sHLAG secretion between both groups. In summary, our data show that immunomodulatory function of the PLSC is not affected by encapsulation. These findings provide good promise for potential use of encapsulated PLSCs for immunomodulation treatment of disease by stem cell therapy.

     

Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.