In systemic autoimmune disorders, autoantibodies develop either directly or indirectly against a variety of cellular components. It is notable that specific autoantibodies are associated with each disorder. Hence, the autoantibodies profiles are important for diagnostic applications. Some of these autoantibodies’ specificities show a unique disease restriction, while others show a broader association with several disorders.[1] As anti-Sm autoantibodies are found exclusively in sera of patients with systemic lupus erythematosus (SLE), whereas anti-U1 ribonucleoprotein (RNP) antibodies found solely in patients with mixed connective tissue disease (MCTD).[1,2] However, low-titer anti-Sm antibodies are also reported in patients with MCTD, and anti-U1-RNP antibodies are in SLE patients.[1,2] Anti-Sjogren’s syndrome-related antigen A (SSA/Ro) autoantibodies are not only found in Sjogren’s syndrome but also in patients with SLE, whereas autoantibodies against histone are exclusively found in druginduced lupus erythematosus.[2] This clinical and serological heterogeneity seems to be complex but clearly associated with specific autoantibodies. It is also established that immune response against self antigen(s) could result as a consequence of several factors such as cross reactions between self-antigens and foreign antigens, dysfunctionality in random B-cell activity or possibly due to genetic predisposition.[3,4] In recent years, reactive oxygen species (ROS) or reactive nitrogen species (RNS) have gained substantial attention as plausible causative agents that directly or indirectly play their pathogenic role in several human disorders.[5,6] In chronic inflammatory conditions, free radicals such as hydroxyl radicals, superoxide, singlet oxygen, nitric oxide, and peroxynitrite are formed in considerably higher amounts due to oxidative stress.[5,7] Peroxynitrite is an oxidant and nitrating species and is well known for its ability to damage a variety of molecules in cells.[8,9] In our previous studies, we found high-titer autoantibodies specific for peroxynitritedamaged thymidine-monophosphate in sera of patients with SLE and showed a positive association with SLE disease activity index.[10,11] In another study, we showed for the first time that mitochondrial DNA after modification with peroxynitrite becomes immunogenic and was found to be a potential immunogen for the production of antibodies in SLE patients.[12] Furthermore, we also reported that oxidized forms of chromatin were well recognized by SLE autoantibodies.[13] Not only have these, we also demonstrated that SLE autoantibodies also recognize 4-hydroxy-2-nonenaldamaged histone H2A.[14] Hydroxyl radicals are now considered as one of the most powerful reactive species and very well known for their biomolecular damage in various pathological conditions.[15-18] In one of our previous studies, we demonstrated that antibodies against hydroxyl radicals modified human serum albumin (HSA) resembled the diverse antigen(s) binding characteristics of SLE autoantibodies.[19] This notable feature was later on confirmed by direct screening of circulating SLE autoantibodies toward hydroxyl radicalmodified HSA[20] By applying various immunological assays, our data demonstrated high degree of anti-hydroxyl-modified HSA antibodies in SLE patients.[20] Furthermore, we also demonstrated that prime antioxidant enzymes, superoxide dismutase and catalase, themselves oxidized by hydroxyl radicals and their oxidized forms were well recognized by circulating antibodies of SLE patients.[21,22] Not only in SLE, we also screened sera of patients with rheumatoid arthritis (RA) and found elevated levels of autoantibodies against hydroxyl radical-damaged immunoglobulin G,[23] suggesting a similar mechanism of oxidative damage in RA. 8-Hydroxydeoxyguanosine (8-oxodG) is a well-known biomarker of oxidative DNA damage.[2] Studies have shown that isolated lymphocytes from RA or SLE patients contain abnormally higher levels of 8-oxodG,[2] indicating oxidative DNA damage in these patients and also provide further support for the onset of a free radical-mediated systemic autoimmunity. Excess generation of oxygen/nitrogen free radicals has also been implicated in the induction of cancer via oxidative damage of cellular components at the biomolecular level.[24,25] Not only in cancer, these radicals are also known as causative agents for several other human disorders including Parkinson’s disease, multiple sclerosis, vitiligo, and alopecia areata.[2,7,26,27] In systemic autoimmune diseases such as SLE or RA, anti- DNA autoantibodies and DNA-anti-DNA antibody immune complexes are known to deposit in the joints and promote inflammation.[28] Due to inflammation, the phagocytic cells become active and induce the release of free radicals. However, when their levels exceed the normal range, these reactive species start to penetrate inside the cellular membrane and induce nuclear DNA damage, which further possibly induce the onset of systemic autoimmunity against nucleic acid antigens.[1,2,28] Native DNA is no longer regarded as an initiating immunogen for systemic autoimmunity because immunization with native DNA does not produce RA/SLE-like symptoms.[2] The most eligible candidates could be denatured/modified DNA or RNA or their polynucleotides.[9-12] It is now well-documented that anti-DNA autoantibodies found characteristically in patients with SLE and most importantly have a strong binding ability to free radical-damaged nucleic acid samples.[2,9-12] Therefore, it is assumed that oxygen/nitrogen reactive radicals formed in-vivo can induce nucleic acid damage, thus altering their structure/immunogenicity, resulting antibodies possibly cross-react with native DNA. The detection of 8-oxodG in the immune complexes derived from SLE or RA patients[29] provides further evidence for the involvement of biomolecular damage in systemic autoimmunity. In short, the mechanism(s) involved in the generation of autoantibodies for systemic autoimmunity has not yet been completely defined. The initial antigen(s) against which autoantibodies are generated remains in debate and seems to be highly controversial and needs to be further explored. In systemic autoimmune disorders, it is postulated that oxygen/nitrogen free radicals generated by phagocytes cause direct oxidative biomolecular damage and make them antigenic for the generation of autoantibodies. Alternatively, a flaw in the apoptotic control or delayed in the elimination of apoptotic cells provides persistent interaction between oxygen/nitrogen reactive radicals and apoptotic cellular macromolecules including the components of nucleic acids or proteins, resulting the generating neo-epitopes for the onset of systemic autoimmunity.

Background: Acute diarrhea constitutes a major global burden to morbidity and mortality in under-five children. Research has shown that micronutrient zinc plays a pivotal role in childhood diarrhea; however, there are contradictory reports of its therapeutic benefit across the various causative enteropathogens. Objectives: The aim of the study was to determine the prevalence of viral etiology (rotavirus, adenovirus, and norovirus) and compare the serum zinc levels of children with acute diarrhea. Methods: A comparative cross-sectional study in which 100 hospitalized children with acute diarrhea aged one–59 months and 100 controls were recruited. Viruses were investigated from stool specimens using the immunochromatographic technique, while serum zinc was determined through the colorimetric method. Data analysis was with SPSS 20 software package. Results: The prevalence of viruses in the subjects was 62.0% with rotavirus isolated in 30 (30.0%) of the patients, while adenovirus and norovirus were detected in 21 (21.0%) and 11 (11.0%) patients, respectively. Rotavirus was the only virus detected in 2 (2.0%) of the controls. The mean serum zinc level of 65.3 ± 7.4 μg/dl in the subjects was significantly lower than 69.0 ± 6.5μg/dl in the controls (P < 0.001). The prevalence of zinc deficiency in the subjects (47.0%) was significantly higher than 32.0% in the controls (P = 0.030). The mean serum zinc levels differed significantly among the viruses isolated in the subjects (P < 0.001). Conclusions: Viruses contribute largely to etiology of acute diarrhea in Nigerian under-five children. Zinc deficiency was also highly prevalent in the study population. The serum zinc levels varied significantly across the different viruses isolated.

Objectives: Although there is evidence that nonsteroidal anti-inflammatory drugs (NSAID) (e.g., celecoxib [Cxb]) can reduce the occurrence of cancer, the precise mechanism remains under study. The current study aimed to investigate the possible antitumor activity of a selective cyclooxygenase-2 inhibitor on solid tumors, its effect on antioxidant status, and ability to prevent angiogenesis. Materials and Methods: Solid carcinomas were induced in female Swiss albino mice. Fifty adult female mice were randomly selected and categorized into five groups. The effects of Cxb on hepatic oxidative parameters and the serum level of vascular endothelial growth factors (VEGF) were investigated in parallel to liver histopathological examinations. Biochemical measurements of hepatic malondialdehyde, superoxide dismutase (SOD) activity, hepatic catalase (CAT) activity, and reduced glutathione (GSH) were estimated in liver homogenates prepared from mice in each study group. Results: The induction of solid tumors in female albino mice was associated with a significant elevation in hepatic lipid peroxidation, whereas the activity of antioxidant enzyme NSAID and CAT was significantly decreased. The level of reduced GSH was decreased. Serum levels of VEGF were significantly increased in tumor-bearing mice compared with normal control mice. These changes were ameliorated when mice were treated with Cxb either before or after the induction of tumors. Antioxidant enzymes were significantly increased, and the serum level of VEGF was significantly reduced compared with the levels in tumor-bearing mice. Conclusion: Cxb exerts antitumor activity through antioxidative and antiangiogenic activities.

Objective: This study aimed to assess the relationship between chemerin and visfatin concentrations and insulin resistance in Saudi women with hyperthyroidism. Materials and Methods: Seventy healthy participants and 70 participants with hyperthyroidism were recruited for the study. Concentrations of chemerin, visfatin, thyroid profile, fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Results: Hyperthyroid patients showed significantly higher concentrations of fasting glucose and insulin (P < 0.001) and significant increases in HOMA-IR values than the control group. Spearman’s correlation coefficient analysis showed that thyroidstimulating hormone was negatively correlated with glucose, insulin, and HOMA-IR, while free triiodothyronine was positively correlated with the same parameters. Total triiodothyronine and total thyroxine also showed a significant positive correlation with glucose, and the levels of thyroglobulin were also positively correlated with insulin and HOMA-IR. Furthermore, chemerin levels correlated positively with glucose, insulin, and HOMA-IR. Inversely, visfatin was negatively correlated with insulin and HOMA-IR. Conclusion: A significant relationship was observed between adipokines and thyroid profile, glucose, insulin, and insulin resistance in hyperthyroid patients. This suggests that visfatin and chemerin levels might affect insulin sensitivity in conjunction with thyroid hormones and thus may alter the metabolism of glucose and leads to insulin resistance.

Background:  Human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) is a global health problem. Since Saudi Arabia is becoming more open to the world, it is important to assess future doctors’ knowledge, attitudes, and practices (KAPs) regarding HIV/AIDS and people living with HIV (PLHIV). Materials and Methods: This cross-sectional study included 204 male medical students of Qassim University who answered a self-administered questionnaire about HIV KAPs. Results: The mean HIV knowledge (HK) and attitude scores were 11.62 (64.5%) and 37.82 (67.5%), respectively. Positive correlations were observed between HK and attitude (r = 0.266) and HK and academic year (r = 0.277). No significant correlation was found between attitude and academic year (r = 0.097). More than half of the students exhibited ignorance about some modes of transmission such as deep kissing and vertical transmission. Around 81% of the students stated that they would not visit the homes of friends with HIV-infected members. Furthermore, 73.1% of the participants indicated that they would not provide care to HIV-positive relatives in their own homes. Conclusions: The findings show a modest level of HK and negative attitudes toward PLHIV. The study identified the main knowledge gaps in the transmission and prevention of HIV. Educational institutions should tailor their educational approach based on the identified gaps, which might help to ease the stigma and negative attitudes.

Objective: Sambucus nigra commonly known as Bilsaan is used extensively in traditional medicine in Saudi Arabia to treat various types of illness. The establishment of safe dose of S. nigra is crucial while considering health-promoting benefits as exposure to excess amount may cause undesirable effects. The aim of the present study was to evaluate the acute oral toxicity of ethanolic (Eth) and methanolic (Meth) extracts from the bark of Bilsaan (Bil) in mice. Materials and Methods: The acute oral toxicity study of Eth-Bil and Meth-Bil extracts was carried out by the administration of 10, 100, and 1000 mg/kg body weight to mice in the 1st phase. According to the observation of the 1st phase, the Eth-Bil extract was given 50, 100, 200, and 400 while Meth-Bil was administered 200, 400, 800, and 1600 mg/kg body weight. Results: The LD50 of the S. nigra (Bilsaan) methanol and ethanol extracts in mice was determined to be 31.62 mg/kg body weight for both of the extracts as calculated by Lorke’s method. The gross observation of systemic organs demonstrated 10–90% increase in the weight of organs of animals treated with increasing concentration of extracts in comparison to control. Similarly, the hematological analyses also showed abnormality and reduction in total leukocytes count exposed with the higher concentration of extracts. Conclusions: The results indicate that the oral administration of Eth-Bil and Meth-Bil extracts produce a significant toxic effect in mice but support in the establishment of safe dose range, as the intake of high doses of S. nigra (Bilsaan) extracts may exhibit mild organ toxicity.

Histoplasmosis also called as “ Darling’s Disease ” is a community-acquired primary pulmonary disease caused by inhalation of dust containing spores of soil-dwelling dimorphic fungi, Histoplasma capsulatum. Presentation of fungi in the oral cavity is usually rare and is generally associated with an immunocompromised state. Here, we present a rare case of histoplasmosis in an immunocompetent patient, with discrete oral presentation, that initially mimicked acute necrotizing ulcerative gingivitis. Gingival biopsy confirmed the diagnosis of histoplasmosis, which responded favorably to the initial treatment with intravenous amphotericin and later to oral itraconazole. Thus, a vigilant approach is paramount in reducing the fatality due to disease.