Ahmed M. Al-Hakami

Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitts lymphoma (BL), Hodgkins disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies

Differentiated mesenchymal stem cells ameliorate cardiovascular complications in diabetic rats

Cardiovascular manifestations are one of the major complications of type 1 diabetes mellitus (T1DM) and supersede the slow progression of DM in most cases as the leading cause of mortality. There have been many studies and trials in regenerating the functional β-cells of islets from mesenchymal stem cells (MSCs) with varied success. The effect of MSCs ex vivo differentiated to mimic functional insulin-secreting β-cells of islets and their impact on restoration of diabetic complications and transplantation via systemic delivery have not been well studied. In the current study, bone marrow MSCs differentiated to insulin-secreting β-cells are used to treat STZ-induced diabetic rats. The post-homing effects of the differentiated MSCs (dMSCs) were endogenous with definite reversal of diabetic parameters. Consequently, the altered cardiac functions like heart beat rate, left ventricular performance, contractility index and physiological body weight gain due to hyperglycemia were amelorated into normacy. The primary onset cardiac perfomance and the endothelial activation were well evidenced by high fibrinogen levels and systolic blood pressure (SBP) being reversed on the treatment by dMSCs. Further high basal [Ca2+]c in isolated endothelial cells and thereby increased ROS confirmed the endothelial activation. The levels of pro-apoptotic makers p53 and Bax were highly expressed in the diabetic groups indicating oxidative stress through ROS induced by high cytosolic calcium skewing the cells towards apoptosis. The expression of the anti-apoptotic marker Bcl-2 was observed to be low in the diabetic group further augmenting the stress state of endothelial cells (ECs) in T1DM. Restoration of [Ca2+]c chelates ROS and the subsequent reversal of pro- and anti-apoptotic markers after the successful treatment of dMSCs proved that endogenous reconstitution of insulin secretion improves diabetic-induced cardiac manifestations.

Aggressive cutaneous zygomycosis caused by Apophysomyces variabilis in an immunocompetent child

A zygomycetous fungus was observed in a biopsy of a 9-year-old male. The patient was presented with severe cutaneous lesions subsequent to a traumatic car accident. Following fungal detection, antifungal treatment was prescribed but condition deteriorated rapidly and above knee amputation was done as lifesaving and to control fungal infection. Analysis of the 28 S rRNA gene (accession KT149770) aligned the isolate with members of the genus Apophysomyces and the pathogen was identified as Apophysomces variabilis.

Pattern of thyroid, celiac, and anti-cyclic citrullinated peptide autoantibodies coexistence with type 1 diabetes mellitus in patients from Southwestern Saudi Arabia

Objectives: To investigate the seroprevalence of coexisting autoantibodies among type 1 diabetes mellitus (T1DM) patients, and to look for possible correlations with age at diagnosis, diabetes duration, and glycemic control. Methods: This is a cross-sectional study conducted at Aseer Central Hospital, Abha, Kingdom of Saudi Arabia from March 2013 to June 2014. A total of 202 T1DM patients were screened for serum anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), anti-tissue transglutaminase (aTTG), anti-endomysial (EMA), and anti-cyclic citrullinated peptide (anti-CCP) antibodies along with glycated hemoglobin, and biometric data. Results: From the 202 T1DM patients (96 males, and 106 females) (mean age: 11.3 years), 33 (16.3%) were positive for thyroid autoantibodies. Specifically, 19 (9.4%) were positive for TG and 25 (12.8%) were positive for TPO, and 11 were double positive. There were 21 (10.4%) patients that showed a double positive for both aTTG-IgA and EMA, and only one case of T1DM was positive for anti-CCP. No significant correlations were noticed between the presence of autoantibodies and the age at diagnosis, diabetes duration, body mass index, and glycemic control. Conclusion: The prevalence of thyroid and celiac disease autoantibodies is high among T1DM patients, while anti-CCP remains low and might be weakly associated with T1DM in the southwestern region of Saudi Arabia. No significant correlation between the age at T1DM diagnosis, duration, and glycemic control, and the presence of autoantibodies was found.

Basidiobolus haptosporus-like fungus as a causal agent of gastrointestinal basidiobolomycosis and its link to the common house gecko (Hemidactylus frenatus) as a potential risk factor

Basidiobolus spp. are a significant causal agent of infections in man and animals including gastrointestinal basidiobolomycosis (GIB). Little information is available on how these infections are acquired or transmitted, apart from the postulation that environmental sources are implicated. This study aimed to identify Basidiobolus spp. from GIB patients and from the house gecko as a possible source of infection in Aseer, Saudi Arabia. Basidiobolus spp. were isolated from patient specimens (colonic mass biopsy) and from house gecko (gut contents) from Muhayil Aseer areas, in southern Saudi Arabia, using Sabouraud dextrose agar (SDA) which was incubated aerobically for up to three weeks at 30°C. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Cultured specimens from humans and geckos revealed phenotypically similar zygomycete-like fungi which conform to those of Basidiobolus species. The strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity with B. haptosporus and 99.97% with B. haptosporus var. minor but have a relatively remote similarity to B. ranarum (99.925%). One isolates from a gecko (L3) fall within the sub-clade encompassing B. haptosporus strain NRRL28635. The study strongly suggests a new and a serious causal agent of GIB related to Basidiobolus haptosporus. The isolation of identical Basidiobolus haptosporus-like strains from humans and lizards from one area is an important step towards identifying risk factors for GIB. Research is underway to screen more environmental niches and fully describe the Basidiobolus strains.

MSCs ameliorates DPN induced cellular pathology via [Ca2+]i homeostasis and scavenging the pro‐inflammatory cytokines

The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co‐culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro‐inflammatory cytokines TNF‐α, IL‐1β, IFN‐ɤ and IL − 12 and control the pro‐apoptotic expression of p53/Bax. Further co‐culture of UCB MSCs have shown to induce anti‐inflammatory cytokines like IL‐4, IL‐10 and TGF‐β and anti‐apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca2+]i and cROS, the portent behind the NFκB/Caspase‐3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p < 0.05) and lowered high amplitude of compound muscle action potentials (CMAPs) (control: 12.36 ± 0.41, DPN: 7.52 ± 0.61 mV, DPN + MSCs: 8.79 ± 0.53 mV, p < 0.05), while slowly restoring the plasma glucose levels. Together, all these results showed that administration of BM or UCB MSCs improved the DPN via ameliorating pro‐inflammatory cytokine signaling and [Ca2+]i homeostasis.

Seroprevalence of coeliac disease in at-risk subjects at the main tertiary hospital, southwest of Saudi Arabia.

BACKGROUND AND STUDY AIMS Coeliac disease (CD) is a gluten-induced autoimmune inflammation of small bowel villi, leading to atrophy and malabsorption. The current study aims to assess the prevalence of CD in high-risk subjects in the Aseer region, southwest of Saudi Arabia and to investigate the associated presentations. PATIENTS AND METHODS This is a retrospective case-finding study of the laboratory records for a 3-year period (2009-2012) at the main tertiary hospital (Aseer Central Hospital). Serum anti-tissue transglutaminase (atTG) and endomysial antibody (EmA) levels were determined along with small intestinal histopathological examination. RESULTS The proportion of cases that tested positive for at least one coeliac antibody marker was 18.4% (58/315). Forty cases underwent endoscopic examination during the analysis, among which 22 were confirmed to have CD. The individual antibody positivity for atTG and EmA was 17.5% and 15.6%, respectively. The most common clinical condition (47%) associated with these markers was type 1 diabetes mellitus (T1DM). Interestingly, gastrointestinal presentations constituted only 11.5%. CONCLUSIONS The rate of CD among hospital requests, including non-gastrointestinal symptomatic patients, at the Aseer main tertiary hospital seems to be high. Determining the prevalence of CD and also investigating the high-risk group commonly affected by CD warrant more screening studies.

Is there is an association between the presence of Staphylococcus species and occurrence of vernal keratoconjunctivitis

Purpose The aim of this study was to identify the association of normal bacterial flora with vernal keratoconjunctivitis (VKC) occurrence in VKC and non-VKC groups. Methods Conjunctival specimens were collected from 18 VKC patients and 22 healthy controls, cultured and identified following standard methods. The association between the presence of bacteria and occurrence of VKC was analyzed using Chi square statistic. Results Comparable bacterial growth was observed in VKC (77.8%) as well as control group (77.2%) (p = 0.970). Analysis of individual bacterial revealed that Staphylococcus aureus was detected more frequently in VKC (27.78% vs. 4.55% in control, p = 0.041) and Staphylococcus epidermidis was found much more commonly in the control eyes (45.45% in control vs. 5.56% in VKC, p = 0.005). Conclusions An aggravating role of S. aureus colonization in the occurrence of VKC, and a possible role of S. epidermidis against the occurrence of VKC were concluded.