Ahmed Al-Shukaili

Effect of Gum Arabic on Oxidative Stress and Inflammation in Adenine–Induced Chronic Renal Failure in Rats

Inflammation and oxidative stress are known to be involved in the pathogenesis of chronic kidney disease in humans, and in chronic renal failure (CRF) in rats. The aim of this work was to study the role of inflammation and oxidative stress in adenine-induced CRF and the effect thereon of the purported nephroprotective agent gum arabic (GA). Rats were divided into four groups and treated for 4 weeks as follows: control, adenine in feed (0.75%, w/w), GA in drinking water (15%, w/v) and adenine+GA, as before. Urine, blood and kidneys were collected from the rats at the end of the treatment for analysis of conventional renal function tests (plasma creatinine and urea concentration). In addition, the concentrations of the pro-inflammatory cytokine TNF-α and the oxidative stress markers glutathione and superoxide dismutase, renal apoptosis, superoxide formation and DNA double strand break frequency, detected by immunohistochemistry for γ-H2AX, were measured. Adenine significantly increased the concentrations of urea and creatinine in plasma, significantly decreased the creatinine clearance and induced significant increases in the concentration of the measured inflammatory mediators. Further, it caused oxidative stress and DNA damage. Treatment with GA significantly ameliorated these actions. The mechanism of the reported salutary effect of GA in adenine-induced CRF is associated with mitigation of the adenine-induced inflammation and generation of free radicals.

Analysis of Inflammatory Mediators in Type 2 Diabetes Patients

The main aim of this study is to assess the inflammatory markers in type 2 diabetes mellitus (T2DM) by measuring some cytokines concentrations and lymphocytes subset and correlate them with other laboratory investigations. Fifty-seven patients with type-2 diabetes and 30 healthy volunteers were enrolled in this study. Data for the C-reactive protein (CRP), haemoglobin, HbA1c, and autoantibody levels were obtained from the patients files. The cytokine concentrations were measured in patients serum using commercially available ELISA assays. Lymphocytes subsets were measured by flow cytometric methods. The levels of IL-1β, IL-6, IL-15, and TNF-α were found to be decreased in T2DM patients, whereas the levels of IL-10, IFN-γ, and caspase-1 were increased, compared to normal controls. T2DM patients with hypertension show significantly decreased levels of IL-1β and caspase-1 compared to patients without hypertension. No significant differences in lymphocytes subset between cases and normal control were observed. Significant correlations were found between HbA1c and IL-6; body mass index (BMI) was significantly correlated with CRP, TNF-α, and phosphate; the weight (Wt) was associated with CRP and IFN-γ. In conclusion, an alteration in the function of the immune system was observed in T2DM patient.

A Comparative Study of Interleukin-1β Production and P2x7 Expression After Atp Stimulation by Peripheral Blood Mononuclear Cells Isolated From Rheumatoid Arthritis Patients and Normal Healthy Controls

Interleukin 1 beta (IL-1β) is a proinflammatory cytokine that is considered to play an important role in the progression of rheumatoid arthritis (RA). A stimulus such as ATP is necessary to cause the release of mature IL-1β, via activation of the P2X7 receptor on monocytes. In this study, the production of IL-1β in whole blood after ATP stimulation and expression of P2X7 receptors in RA and healthy subjects were examined. Blood samples from RA patients or healthy controls were stimulated with ATP in the presence of lipopolysaccharide (LPS). Supernatants were harvested and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA). Expression of P2X7 receptors was measured using flow cytometry. ATP induced significantly higher levels of IL-1β in LPS-activated RA blood samples compared to controls. A significant up-regulation of P2X7 receptor expression on mononuclear cells was observed after overnight incubation with ATP without any significant differences between RA patients and normals. These data suggest that RA patient mononuclear cells are more sensitive to ATP stimulation than healthy individuals perhaps due to genetic polymorphism in the P2X7 gene.

The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease

Alzheimers disease (AD), a neurodegenerative disorder associated with advanced age, is the most common cause of dementia globally. AD is characterised by cognitive dysfunction, deposition of amyloid plaques, neurofibrillary tangles and neuro-inflammation. Inflammation of the brain is a key pathological hallmark of AD. Thus, clinical and immunopathological evidence of AD could be potentially supported by inflammatory mediators, including cytokines, chemokines, the complement system, acute phase proteins and oxidative mediators. In particular, oxidative mediators may actively contribute to the progression of AD and on-going inflammation in the brain. This review provides an overview of the functions and activities of inflammatory mediators in AD. An improved understanding of inflammatory processes and their role in AD is needed to improve therapeutic research aims in the field of AD and similar diseases.

P2X7 receptor gene polymorphism analysis in rheumatoid arthritis

The P2X7 receptor, a member of the P2X family of nucleotide‐gated channels, is predominantly expressed by monocytic cells. The activation of this receptor has been associated with downstream‐signalling cascades, resulting in the release of a number of inflammatory mediators. There are more than 815 single nucleotide polymorphisms (SNPs) that have been described in the human P2X7R gene, but only few have been functionally characterized. The main aim of this study is to determine whether P2X7R gene polymorphisms confer susceptibility to rheumatoid arthritis (RA). A total of 125 patients with RA and 158 healthy volunteers were enrolled in this study. DNA fragment was PCR amplified and sequenced on the AB 3130 Genetic Analyzer. No significant difference in allele frequencies of 489 C→T, 1096 C→G and 1513 A→C polymorphisms, among sporadic cases of RA and healthy controls was found. However, the 1513A/C genotype was significantly associated with the presence of rheumatoid factor and anti‐MCV autoantibody in RA patients. Interestingly, the genotype frequency of 1068 A/A was 0.19 in the RA group and 0.09 in control group (P = 0.025). Consequently, this polymorphism (AA) is two folds greater in the RA group compared to controls. Moreover, this polymorphism was significantly associated with mean concentration of C‐reactive protein in RA patients. In contrast, 946G→A and 1729 T→A were not detected in both groups. As a result, these two polymorphisms are uncommon in Omani Arab population. Polymorphism at position 1068 and 1513 in the P2X7R gene might contribute to the pathogenesis of RA. Moreover, the loss‐of‐function SNP at position 1096 C→G or the gain‐of‐function SNP at position 489 C→T of the P2X7 gene does not appear to be a susceptibility gene locus for the development of RA. Further studies are required to confirm this finding.

Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated Peptide antibodies and rheumatoid factor in omani patients with rheumatoid arthritis.

Rheumatoid factor (RF) is currently used in the diagnosis of rheumatoid arthritis (RA). The discovery of anticitrullinated protein autoantibodies has led to the development of various new tests, such as anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-mutated citrullinated vimentin (anti-MCV) antibodies, to diagnose RA. The aims of this study were to determine the sensitivity and specificity of anti-MCV antibodies in comparison with anti-CCP antibodies and RF in Omani Arab patients with RA and compare our findings with published values from different ethnic groups. The sensitivity of anti-MCV antibodies was 72% with 87% specificity. For anti-CCP antibodies the sensitivity was 52% and the specificity was 97%. The sensitivity of RF was 57% with 94% specificity. Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. Anti-MCV antibodies have the highest sensitivity when compared to anti-CCP antibodies and RF. Anti-MCV antibodies do not appear to be very useful in the diagnosis of RA. However, long-term study is required to find out whether anti-MCV antibodies can be used as predictive test for incidence of RA.

Quantification of CD4+ CD25+ Regulatory T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

Recent animal studies have shown that regulatory T cells play a crucial role in the suppression of the immune response and that depletion of this subset of T cells might lead to development of autoimmune diseases. The aim of this work was to quantify regulatory T cells (CD4+ CD25+) in the peripheral blood of Omani patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA) and correlate these findings with the disease activity of the patients. Thirty patients with SLE, 30 patients with RA and 25 healthy volunteers were enrolled in this study. Patients were divided into highly active or low active groups, depending on the disease activity. Flow cytometer was used to quantify CD4+ CD25+ T cells in the peripheral blood mononuclear cells (PBMC). We found that both highly active SLE (0.242 ± 0.3) and RA (0.56 ± 0.29) patients had significantly (p<0.001) lower levels of CD4+CD25 bright T cells than did normal controls (1.74 ± 0.47%) or patients with low disease activity (SLE=1.54 ± 0.33, RA=1.829 ± 0.76). The decreased number of CD4+CD25 bright T cells during disease activity was restored in remitting phase of SLE patients. This data provides further evidence supporting the hypothesis of defect of regulatory T cells in SLE and RA patients; which may have an important implication in the context of the control of the inflammation and development of autoimmunity.

Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

BACKGROUND AND OBJECTIVE The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca), copper (Cu), iron (Fe) and carcinoembryonic antigen (CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer. METHODS Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perls Prussian blue, Von Kossas, modified rhodanine and immunohistochemical staining methods, respectively. RESULTS Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. CONCLUSIONS Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.