10 years of experience in adopting, implementing and evaluating progress testing for Saudi medical students.

Objectives: The progress test (PT) is a comprehensive examination that is designed to match the knowledge acquisition necessary at graduation and monitors progress during the entire period of an undergraduate program. Qassim College of Medicine (QCM) began using the multi-institutional PT in the Kingdom of Saudi Arabia (KSA). This study aimed to determine if the PT can be utilized to assess the progress of medical students at different Saudi medical colleges with different educational approaches, as well as whether this testing modality could be accepted by other colleges. Methods: Beside the establishment of a PT committee, comprehensive blueprinting was crafted to sample 200 A-type multiple choice questions (MCQs) from different disciplines. The PT is a paper-and-pencil model and is answered in a 4-h period. All PT items followed a uniform design. Results: In total, 13 rounds of the progress test have been conducted. The number of participating colleges increased from three (with 285 students) in the first test (May 2012) to more than 20 (with >6000 students) in the ninth round (February 2017). The average % scores for first-year students ranged from 3.0% to 7.9% while the average scores for fifth-year students ranged from 34.0% to 43.0%. Conclusion: The conduction of this meticulously crafted test to evaluate knowledge achievement at medical graduation is a fruitful tool and helps to provide constructive feedback for test-takers and other stakeholders relating to their relative positions among other fellows at the national level.

Functional role of human interleukin-32 and nuclear transcription factor-kB in patients with psoriasis and psoriatic arthritis.

OBJECTIVE: Inflammation and its associated cell signaling events have been well documented in psoriasis and psoriatic arthritis. However, the potential for interleukin (IL)-32 and its associated signaling to provoke an inflammatory response or to contribute in the pathogenesis of psoriasis or psoriatic arthritis are still in early phase. This study determined the role of IL-32 and nuclear transcription factor (NF)-κB in patients with plaque psoriasis and psoriatic arthritis. METHODS: Levels of IL-32 were determined in the plasma samples of patients with plaque psoriasis, psoriatic arthritis, and normal healthy subjects by human IL-32-specific Sandwich enzyme-linked immunosorbent assays. To investigate the role of a transcription factor in these patients, activated NF-κBp65 levels were determined in the peripheral blood mononuclear cells (PBMCs) by highly sensitive NF-κB transcription factor kit. RESULTS: The levels of IL-32 in the plasma samples of plaque psoriasis or psoriatic arthritis patients were found to be significantly higher as compared with the levels of IL-32 present in the normal human plasma samples (P < 0.01). Levels of activated NF-κB were also found higher in plaque psoriasis or psoriatic arthritic patients as compared with the PBMCs of healthy humans (P < 0.05). CONCLUSIONS: This study shows the role of IL-32 and NF-κB in plaque psoriasis and psoriatic arthritic patients. Results indicate that IL-32 and NF-κB promote inflammation in patients with psoriasis and psoriatic arthritis. Disruption of IL-32 or NF-κB signaling event might provide a novel target for the management of plaque psoriasis and psoriatic arthritis.

Elevated Gene Expression of Interleukin-32 Isoforms Alpha, Beta, Gamma, and Delta in the Peripheral Blood of Chronic Psoriatic Patients.

Inflammatory-mediated reactions have been implicated as contributors in a number of dermatological disorders, including psoriasis. However, the potential of interleukin (IL)-32 and its isoforms to contribute to the pathogenesis of psoriasis remains unexplored. This study was undertaken to investigate the role of IL-32 and its isoforms IL-32α, IL-32ß, IL-32γ, and IL-32δ in the peripheral blood of psoriatic patients. The majority of chronic plaque psoriatic patients showed elevated IL-32 mRNA levels in the peripheral blood mononuclear cells (PBMCs) as compared with the levels of IL-32 mRNA in PBMCs of healthy controls (p = 0.001). To further investigate the role of elevated levels of IL-32 in psoriatic patients, IL-32 isoforms mRNAs were determined. All tested isoforms IL-32α, IL-32ß, IL-32γ, and IL-32δ were overexpressed in psoriatic patients PBMCs as compared with healthy controls' PBMCs (p < 0.05). IL-32α mRNA expression was also significantly higher as compared with all other isoforms of IL-32 in PBMCs of psoriatic patients (p < 0.001). In short, this is the first study that shows the role of IL-32 and its isoforms in the peripheral blood of psoriatic patients. Our novel findings support an association between elevated levels of IL-32 and psoriasis. The data also suggest that a major proinflammatory response of IL-32 may derive from IL-32α isoform in psoriasis.

Epigallocatechin-3-O-gallate up-regulates microRNA-199a-3p expression by down-regulating the expression of cyclooxygenase-2 in stimulated human osteoarthritis chondrocytes.

Osteoarthritis (OA) is a most common form of arthritis worldwide leading to significant disability. MicroRNAs (miRNAs) are non-coding RNAs involved in various aspects of cartilage development, homoeostasis and pathology. Several miRNAs have been identified which have shown to regulate expression of target genes relevant to OA pathogenesis such as matrix metalloproteinase (MMP)-13, cyclooxygenase (COX)-2, etc. Epigallocatechin-3-O-gallate (EGCG), the most abundant and active polyphenol in green tea, has been reported to have anti-arthritic effects, however, the role of EGCG in the regulation of miRNAs has not been investigated in OA. Here, we showed that EGCG inhibits COX-2 mRNA/protein expression or prostaglandin E2 (PGE2 ) production via up-regulating microRNA hsa-miR-199a-3p expression in interleukin (IL)-1ß-stimulated human OA chondrocytes. This negative co-regulation of hsa-miR-199a-3p and COX-2 by EGCG was confirmed by transfection of OA chondrocytes with anti-miR-199a-3p. Transfection of OA chondrocytes with anti-miR-199a-3p significantly enhanced COX-2 expression and PGE2 production (P < 0.001), while EGCG treatment significantly inhibited anti-miR-199a-3p transfection-induced COX-2 expression or PGE2 production in a dose-dependent manner. These results were further re-validated by co-treatment of these transfection OA chondrocytes with IL-1ß and EGCG. EGCG treatment consistently up-regulated the IL-1ß-decreased hsa-miR-199a-3p expression (P < 0.05) and significantly inhibited the IL-1ß-induced COX-2 expression/PGE2 production (P < 0.05) in OA chondrocytes transfected with anti-hsa-miR-199a-3p. Taken together, these results clearly indicate that EGCG inhibits COX-2 expression/PGE2 production via up-regulation of hsa-miR-199a-3p expression. These novel pharmacological actions of EGCG on IL-1ß-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds inhibit cartilage breakdown or pain by up-regulating the expression of microRNAs in human chondrocytes.

Integrated Study of Globally Expressed microRNAs in IL-1ß-stimulated Human Osteoarthritis Chondrocytes and Osteoarthritis Relevant Genes: A Microarray and Bioinformatics Analysis.

This study was undertaken to identify and characterize the globally expressed microRNAs (miRNAs) involved in interleukin-1ß (IL-1ß)-induced joint damage and to predict whether miRNAs can regulate the catabolic effects in osteoarthritis (OA) chondrocytes. Out of 1347 miRNAs analyzed by microarrays in IL-1ß-stimulated OA chondrocytes, 35 miRNAs were down-regulated, 1 miRNA was up-regulated, and the expression of 1311 miRNAs remained unchanged. Bioinformatics analysis showed the key inflammatory mediators and key molecular pathways are targeted by differentially expressed miRNAs. Novel miRNAs identified could have important diagnostic and therapeutic potentials in the development of novel therapeutic strategies for pain managements in OA.

Sepsis in Buraidah Central Hospital, Qassim, Kingdom of Saudi Arabia.

OBJECTIVES: Severe sepsis is a major public health concern and a frequent cause of intensive care unit (ICU) admission with a high fatality rate. Higher (Sequential Organ Failure Assessment score) SOFA score and co-morbidity of acute renal failure (ARF) are risk factors contributing to fatal outcome. This work was meant to study the epidemiology of sepsis in Buraidah central hospital. METHODS: This is a descriptive study conducted in the period from January 1, 2012, to June 29, 2012 to determine the epidemiology (incidence, clinical characteristics) and the outcome of sepsis in Buraidah hospital, Saudi Arabia. RESULTS: Out of 387 patients admitted to ICU, 62 (16%) patients had sepsis, their mean (SD) age was 62.7 (21.3) years. Three quarters of them 47 (75.8%) presented with septic shock. The median APACHE II score was 26.5 (8 to 48) and SOFA score 11 (5 to 21). The mean of duration of hospital stay was 11.95 days. The most frequent infection site was the pulmonary (69.5%). There were 37 isolated organism, gram-negative organisms (13; 35.13%) were the predominant isolates. There were 25 (40.3%) deaths; the majority of the deaths were due to septic shock 20(80%). There was a significant difference between deaths and the survivors, in the APACHI II score, SOFA score), and whether ventilated or not. CONCLUSIONS: There was a high incidence of septic shock (and higher mortality) among the patients admitted to the ICU of Buraidah central hospital, especially among the elderly patients with respiratory infections.

Molecular Genetic of Atopic dermatitis: An Update.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date.

MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-κB pathway in human osteoarthritis chondrocytes.

Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1ß (IL-1ß)-mediated induction of iNOS can be regulated by microRNA-26a-5p (hsa-miR-26a-5p) in OA. Bioinformatics approaches show that 3'UTR of iNOS mRNA contained the 'seed-matched-sequence' for hsa-miR-26a-5p. IL-1ß-induced expression of iNOS correlated with the down-regulation of miR-26a-5p in human OA chondrocytes. hsa-miR-26a-5p directly suppressed the luciferase activity of 3'UTR-iNOS reporter clone. Transfection with pre-miR-26a-5p induced marked silencing of iNOS expression. Activation of NF-κB pathway down-regulated the expression of hsa-miR-26a-5p and induced iNOS expression. In short, this is the first report that shows hsa-miR-26a-5p is a direct regulator of iNOS expression in human chondrocytes. hsa-miR-26a-5p may be an important regulator of human cartilage homeostasis and a new target for OA therapy.

Recognition of oxidized albumin and thyroid antigens by psoriasis autoantibodies. A possible role of reactive-oxygen-species induced epitopes in chronic plaque psoriasis.

OBJECTIVES: To investigate the role of reactive-oxygen-species (ROS) induced epitopes on human-serum-albumin (HSA) and thyroid antigens in psoriasis autoimmunity.   METHODS: This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS)-induced epitopes on protein (ROS-epitopes-albumin) was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs) with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26) against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22).  RESULTS: The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera.   CONCLUSION: Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis.

Oxidized tyrosinase: A possible antigenic stimulus for non-segmental vitiligo autoantibodies.

BACKGROUND: Vitiligo is a common pigmentary disorder, the precise etiology of which remains obscure. Tyrosinase, a key enzyme involved in melanin synthesis, has now been implicated as an autoantigen for vitiligo patients, but it is not clear how this prevalent protein becomes antigenic in vitiligo. OBJECTIVE: To investigate the status and contribution of oxidized tyrosinase in vitiligo and to explore whether oxidized tyrosinase has a role in disease progression. METHODS: Tyrosinase was modified by reactive-oxygen-species (ROS). Binding characteristics of antibodies in vitiligo patients (n=25) with varying disease duration (DD) and disease severity were screened against ROS-modified tyrosinase (ROS-tyrosinase) by immunoassays and their results were compared with healthy controls (n=23). RESULTS: The ROS caused extensive alterations in conformation and function of tyrosinase. Protein-A purified IgGs from vitiligo patients (Vt-IgG) showed strong binding to ROS-tyrosinase in comparison with IgGs from healthy controls (p<0.001). Interestingly, not only was there an increased number of subjects positive for anti-ROS-tyrosinase-IgGs, but also the levels of these IgGs were significantly higher among vitiligo patients, whose DD were ≥10 years as compared to patients with short DD (<10 years). In addition, a significant correlation was observed between the levels of anti-ROS-tyrosinase-IgGs and the patients' ages or with disease severity. Experimentally induced anti-ROS-tyrosinase-IgGs show reactivity with tyrosinase from vitiligo patients. Furthermore, vitiligo patients had lower levels of tyrosinase activity compared with healthy controls. Not only these, levels of carbonylation were also higher among vitiligo patients whose DD were ≥10 years as compared to patients with DD<10 years. CONCLUSIONS: This is the first study to demonstrate the role of oxidized tyrosinase in vitiligo. Our novel results support an association between oxidized tyrosinase and vitiligo autoimmunity. The stronger antibodies response to oxidized tyrosinase in vitiligo patients with higher DD or with severe patients suggests that oxidized tyrosinase may be a useful biomarker in evaluating the progression of vitiligo and in elucidating the mechanisms of disease pathogenesis.

Interleukin-4 -590 T>C and interleukin-4 receptor Q551R A>G gene polymorphisms in Saudi cases with alopecia areata.

OBJECTIVES: Immunogenetic factors are known to play a role in the pathogenesis of alopecia areata (AA). This study aimed at investigating the association between AA with the polymorphisms of interleukin-4 (IL-4) promoter and receptor (IL-4R) genes. PATIENTS AND METHODS: This work is a case-control study that was conducted on 76 AA patients from Qassim region, Saudi Arabia. Patients were compared with 93 normal healthy controls from the same locality. Genomic DNA was extracted and processed using real-time PCR amplification for characterization of IL-4 -590 T>C and IL-4R Q551R A>G gene polymorphisms. RESULTS: Cases of AA showed a higher frequency of the IL-4 -590 CC homozygous genotype compared with controls (63.2 vs. 53.8%, P>0.05) with a lower frequency of the TT genotype (5.3 vs. 10.8%); yet, both were statistically nonsignificant (P>0.05). Regarding the IL-4R Q551R A>G polymorphism, cases and controls showed nearly equal frequencies of all variants, that is, with no significant difference. Although the frequency of the IL-4 C and the IL-4R A alleles was higher among cases than among controls (78.9 vs. 71.5% and 78.8 vs. 72.6%, respectively), this was also statistically nonsignificant (P>0.05). Comparing case subgroups in terms of their age of onset, sex, disease severity, consanguinity, and family history showed no statistically significant difference regarding the studied genetic variant. CONCLUSION: IL-4 -590 and IL-4R Q551R gene polymorphisms are not associated with the susceptibility and the clinical pattern of AA in Saudi patients. We recommend further research studies involving the estimation of cytokines both in the serum and in the local skin lesions or in cultured skin cells to figure out whether Th1 or Th2 pathways play a specific role in the pathogenesis of AA.

Treatment of vitiligo patients by excimer laser improves patients' quality of life.

BACKGROUND: Vitiligo can negatively affect patients' quality of life (QoL). Assessment of QoL provides relevant information about treatment benefits. OBJECTIVES: To examine the effects of excimer laser treatment on vitiligo patients' QoL and to identify overall patient satisfaction. The literature review failed to show any study concerning the same field. METHODS: A total of 134 vitiligo patients (with 386 lesions) were studied. The Dermatology Life Quality Index (DLQI) was used to assess the effect of excimer laser treatment on patients' QoL. A visual analogue scale (VAS) was used to rate patients' overall life satisfaction and disturbance. RESULTS: Excimer laser treatment significantly improved QoL in vitiligo patients, with improvement observed in five of six DLQI domains. Treatment-induced changes in the VAS score showed a significant decline in life disturbance and improvement in life satisfaction. Multivariate analysis revealed that sex and treatment duration were independent factors influencing treatment outcomes. CONCLUSIONS: Treatment of vitiligo with excimer laser can positively influence patients' QoL. Patients with multiple focal lesions should be treated by excimer laser even if some lesions may not show significant clinical improvement.

Treatment of vitiligo patients by excimer laser improves patients' quality of life.

BACKGROUND: Vitiligo can negatively affect patients' quality of life (QoL). Assessment of QoL provides relevant information about treatment benefits. OBJECTIVES: To examine the effects of excimer laser treatment on vitiligo patients' QoL and to identify overall patient satisfaction. The literature review failed to show any study concerning the same field. METHODS: A total of 134 vitiligo patients (with 386 lesions) were studied. The Dermatology Life Quality Index (DLQI) was used to assess the effect of excimer laser treatment on patients' QoL. A visual analogue scale (VAS) was used to rate patients' overall life satisfaction and disturbance. RESULTS: Excimer laser treatment significantly improved QoL in vitiligo patients, with improvement observed in five of six DLQI domains. Treatment-induced changes in the VAS score showed a significant decline in life disturbance and improvement in life satisfaction. Multivariate analysis revealed that sex and treatment duration were independent factors influencing treatment outcomes. CONCLUSIONS: Treatment of vitiligo with excimer laser can positively influence patients' QoL. Patients with multiple focal lesions should be treated by excimer laser even if some lesions may not show significant clinical improvement.

Mitochondrial DNA acquires immunogenicity on exposure to nitrosative stress in patients with vitiligo.

Vitiligo is a common pigmentary skin disorder of unknown etiology. Many studies show the defective mitochondrial functionality in vitiligo patients, but the potential role of mitochondrial DNA (mtDNA) in the pathogenesis of vitiligo remains to be investigated. Recent evidences demonstrate that mitochondria possess their own nitric-oxide-synthase and can produce endogenous peroxynitrite (ONOO(-)). This study was undertaken to investigate the role of ONOO(-)-modified-mitochondrial-DNA (ONOO(-)-mtDNA) in vitiligo autoimmunity. Our data revealed that ONOO(-)-induced modifications in mtDNA caused structural alterations. Specificity of immunoglobulin G (IgG) from vitiligo patients (n=26) and controls (n=25) were analysed towards ONOO(-)-mtDNA. Vitligo-IgG samples (Vt-IgG) show preferential binding to ONOO(-)-mtDNA in comparison with native mtDNA (p<0.01). Anti-ONOO(-)-mtDNA-IgG show cross-reactivity with isolated DNA from vitiligo patients. Furthermore, levels of anti-ONOO(-)-mtDNA-IgG, inducible-nitric-oxide-synthase (iNOS), nitric oxide (NO) and nitrotyrosine were higher among vitiligo patients whose disease durations (DD) were ⩾5 years as compared to patients with lower DD (DD<5 years). In conclusion, this is the first study to demonstrate the role of ONOO(-)-modified mtDNA in vitiligo patients. Our data provide an important insight into the immunological mechanisms occur in vitiligo. The ONOO(-)-mtDNA may be useful in elucidating the mechanisms of disease pathogenesis.

Correlation of clinical efficacy and psychosocial impact on vitiligo patients by excimer laser treatment.

BACKGROUND AND OBJECTIVES: Vitiligo is a difficult disease to treat. Recently, a 308-nm excimer laser has been shown to be effective in treating vitiligo. In addition, the patients with vitiligo have impairment in their quality of life. The aim of the study was to investigate the clinical efficacy, safety, and psychosocial impact after treating vitiligo with the 308-nm excimer laser. DESIGN AND SETTINGS: A prospective clinical trial conducted at dermatology clinics of hospitals affiliated with Qassim University, Saudi Arabia, from May 2012 to February 2013. PATIENTS AND METHODS: Forty-eight patients with 105 vitiliginous patches were treated using a 308-nm excimer laser. The treatment was performed twice per week for a maximum of 48 treatments or 100% repigmentation of lesions whichever was achieved first. The assessment of the clinical response and recording of side effects were performed biweekly. RESULTS: Out of 105 lesions in these patients, 63 lesions (60.0%) achieved over 75% repigmentation by laser treatment, 12 lesions (11.4%) showed 51% to 75% repigmentation, 9 lesions (8.6%) showed 26% to 50% repigmentation, and another 9 lesions (8.6%) showed 1% to 25% repigmentation, while 12 lesions (11.4%) showed no repigmentation. The average (+/-standard deviation [SD]) number of sessions needed to achieve repigmentation was 16.8 (8.0), whereas the average (+/-SD) number of sessions needed to realize Grade IV repigmentation was 20.2 (15). The type of repigmentation varied between lesions. Diffuse repigmentation was the most common pattern and occurred in 34 lesions (36.6%). Facial lesions responded better than lesions located elsewhere. Skin type did not play a statistically significant role (P=.07) in the lesions response to treatment. All side effects were mild and disappeared shortly after end of treatment sessions. CONCLUSION: The clinical data indicate that the treatment of vitiligo using the 308-nm excimer laser is effective and safe and improves psychosocial quality of life. Lesion location, duration of disease, and treatment duration are factors affecting the clinical and psychological outcome.

Oxidants and anti-oxidants status in acne vulgaris patients with varying severity.

Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls. Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease's activity and to monitor its treatment.

Biochemical and immunological studies on erythrocytes superoxide dismutase modified by nitric oxide in patients with alopecia areata: Implications in alopecia patchy persistent and alopecia universalis.

Alopecia areata (AA) is a non-scarring hair loss disorder that ranges in severity from patchy loss of scalp hair (AA patchy persistent; AAP) to loss of all scalp and body hair (alopecia universalis; AU). The cause of AA is unknown but most evidences support that AA has an autoimmune etiology, where free radicals play an important role. This study was undertaken to investigate the role of nitric oxide (NO) modified erythrocytes superoxide dismutase (eSOD) in AA. Data revealed that NO-induced damage in eSOD caused alteration in hydrophobic or aromatic amino acids and protein carbonyl contents. NO-specific quencher, carboxyl-PTIO further reiterates NO-modifications. Specificity of antibodies from AA patients (n=26) was analyzed toward NO-modified eSOD (NO-eSOD) and their results were compared with healthy controls (n=30). Protein-A purified IgG of AA patients (AA-IgG) showed strong binding to NO-eSOD in comparison with IgG from controls. In addition, AA-IgG from patients with AU recognized NO-eSOD in a greater extent as compared to AA-IgG from patients with AAP. Furthermore, AU patients' sera contained higher levels of NO or carbonyl contents and lower levels of SOD activity compared with AAP patients' or control sera. In conclusion, this is the first study to demonstrate the role of NO-modified-eSOD in AA. Our novel results conclude that perturbations in SOD by NO presenting unique neo-epitopes that might be one of the factors for the antigen driven antibodies induction in AA. Preferential binding of NO-eSOD by AA-IgG pointed out the likely role of NO-eSOD in the initiation/progression of AA.

The ultrastructural effects of long-term use of henna on the albino rat skin.

Tattooing with henna is a routine practice in the Arab world. To the best of our knowledge, no previous studies have evaluated the adverse histological effects following henna tattooing on the ultrastructure of the skin. The objectives of this study were to diagnose the cytopathological alterations induced by commercial henna and to investigate the adverse role of henna when combined with sun ray on the skin. The skin of albino rats was tattooed with natural and black henna for three months, skin samples were examined by transmission electron microscope. In addition, the concentration of lead in henna samples was estimated by using atomic absorption spectrophotometry. The results expanded the understanding of the pathogenesis of henna-induced phytophotodermatitis. We hypothesized that henna-associated additives penetrated the epidermal barrier to gain access to the vascular dermis where the harmful ingredients became concentrated, leading to skin pathology through a dual mechanism. First, these ingredients became re-transported into the epidermis through vesicular trafficking leading to dermo-epidermal blistering and cytoplasmic vacuolization of the stratum basal cells. Following this, cytoplasmic vacuoles poured their content into the nuclei through continuities with the perinuclear cisterna, possibly leading to genetic mutation. The progression of keratinocytes into the next layers became associated with nuclear and cytoplasmic signs of apoptosis with subsequent phagocytosis in other epidermal cells, most probably keratinocytes. The second mechanism of injury was mediated through accumulation of inflammatory cells around capillaries in the dermis with the release of angiogenic and mitogenic mediators resulting in vasculopathy.

4-Hydroxy-2-nonenal modified histone-H2A: a possible antigenic stimulus for systemic lupus erythematosus autoantibodies.

Protein modifications by 4-hydroxy-2-nonenals (HNE) are involved in various diseases. Histones are DNA protective nucleoprotein, which adopt different structures under oxidative stress. This study was undertaken to test the role of HNE-modified-histone-H2A (HNE-H2A) in systemic lupus erythematosus (SLE). Our data revealed that HNE-mediated-lipid peroxidation in histone-H2A caused alteration in histidine, lysine and cystein residues. In addition, protein carbonyl contents were also high in HNE-H2A. HNE-specific quencher, L-carnosine further reiterates HNE-modifications. Specificity of autoantibodies from SLE patients (n=48) were analyzed towards HNE-H2A and their results were compared with sex- and age-matched controls (n=36). SLE autoantibodies show preferential binding to HNE-H2A in comparison with histone-H2A (p<0.0001). Furthermore, HNE-H2A was also detected in SLE peripheral blood mononuclear cells. In conclusion, this is the first study to demonstrate the role of HNE-modified-histone in SLE. Preferential binding of HNE-H2A by affinity purified SLE-IgG pointed out the likely role of HNE-H2A in the initiation/progression of SLE.

Clinical and histopathologic characteristics of skin malignancies in Qassim Region, Saudi Arabia.

BACKGROUND AND OBJECTIVE: The present study was undertaken to assess the pattern of skin malignancies in Qassim region, Kingdom of Saudi Arabia. METHODS: Data of histopathological confirmed cases of skin malignancies were collected from all the referral hospitals of Qassim region during a period from January 2000 to July 2009. RESULTS: Out of 94 cases majority (90.4%) were Saudis, and males (74.5%). The most common malignant skin lesion was BCC (58.5%) followed by SCC (18.1%) and MM (11.7%), respectively. Other malignancies seen were DFSP (4.3%), sebaceous carcinoma (2.1%) and skin secondaries from lung, lymphoma and stomach (4.3%). The most common site was face for BCC, trunk for SCC, and limbs for MM. The DFSP did not show any particular pattern. CONCLUSION: All major types of skin malignancies were seen with patterns similar to those reported from various other regions of Saudi Arabia and other countries except for Kaposi's sarcoma which was not encountered in our study.