Suleiman Al-Hammadi

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics

BackgroundPrevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.ObjectiveThe World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.MethodsWe identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.ResultsCurrently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.ConclusionsWAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.

Cannabinoids Inhibit Cellular Respiration of Human Oral Cancer Cells

Background and Purpose: The primary cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and Δ8-tetrahydrocannabinol (Δ8-THC) are known to disturb the mitochondrial function and possess antitumor activities. These observations prompted us to investigate their effects on the mitochondrial O2 consumption in human oral cancer cells (Tu183). This epithelial cell line overexpresses bcl-2 and is highly resistant to anticancer drugs. Experimental Approach: A phosphorescence analyzer that measures the time-dependence of O2 concentration in cellular or mitochondrial suspensions was used for this purpose. Key Results: A rapid decline in the rate of respiration was observed when Δ9-THC or Δ8-THC was added to the cells. The inhibition was concentration-dependent, and Δ9-THC was the more potent of the two compounds. Anandamide (an endocannabinoid) was ineffective; suggesting the effects of Δ9-THC and Δ8-THC were not mediated by the cannabinoidreceptors. Inhibition of O2 consumption by cyanide confirmed the oxidations occurred in the mitochondrial respiratory chain. Δ9-THC inhibited the respiration of isolated mitochondria from beef heart. Conclusions and Implications: These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.

Population prevalence of asthma and its determinants based on European Community Respiratory Health Survey in the United Arab Emirates

BackgroundNo population study has explored the population distribution of adult asthma in the United Arab Emirates (UAE). The objective is to estimate asthma prevalence in general population in UAE.MethodsUsing standard European Community Respiratory Health Survey (ECRHS) questionnaires and tools, this is a cross-sectional assessment of a random sample of the population in established quotas of the seven Emirates in the UAE. We surveyed 1,220 participants, of which 63.2% were male, and 20.1% were UAE Nationals, with a mean (SD) age of 32.9 (14.1) years.ResultsPrevalence of individual respiratory symptoms from the ECRHS screening questionnaire in all participants were generally ranging 8 - 10%, while participants 20-44 years presented lower prevalence in all symptoms (p < 0.05). The expected male:female ratio of reported wheezing and asthma attacks and its treatment by age was not observed. Participating women reported more individual symptoms than men. Overall, there were 15.4% (95% C.I. 13.5 - 17.5) participants who fulfilled our screening criteria for asthma, while for consistency with ECRHS, there were 12.1% (95% C.I. 10.4 - 14.1) participants who fulfilled the ECRHS asthma definition, being 9.8% (95% C.I. 7.8 - 12.2) of those 20-44 years, that is 8.6% of male and 11.8% of female young adults participating.ConclusionWe conclude that asthma is common in the UAE, and gender differences are not observed in reported asthma symptoms in young adults. This being the first population based study exploring the prevalence of asthma and its determinants in the United Arab Emirates based on the ECRHS.

Measurement of oxygen consumption by murine tissues in vitro

INTRODUCTION A novel in vitro system was developed to measure O₂ consumption by murine tissues over several hours. METHODS Tissue specimens (7-35 mg) excised from male Balb/c mice were immediately immersed in ice-cold Krebs-Henseleit buffer, saturated with 95% O₂:5% CO₂. The specimens were incubated at 37 °C in the buffer, continuously gassed with O₂:CO₂ (95:5). [O₂] was determined as a function of time from the phosphorescence decay rates (1/τ) of Pd(II) meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. The values of 1/τ were linear with [O₂]: 1/τ=1/τo + kq [O₂]; 1/τo=the decay rate for zero O₂, kq=the rate constant in s⁻¹ μM⁻¹. RESULTS NaCN inhibited O₂ consumption, confirming oxidation occurred in the mitochondrial respiratory chain. The rate of respiration in lung specimens incubated in vitro for 3.9≤t≤12.4 h was 0.24±0.03 μM O₂ min⁻¹ mg⁻¹ (mean±SD, n=28). The corresponding rate for the liver was 0.27±0.13 (n=11, t≤4.7 h), spleen 0.28± 0.07 (n=10, t≤5h), kidney 0.34±0.12 (n=7, t≤5h) and pancreas 0.35±0.09 (n=10, t≤4h). Normal tissue histology at hour 5 was confirmed by light and electron microscopy. There was negligible number of apoptotic cells by caspase 3 staining. DISCUSSION This approach allows accurate assessment of tissue bioenergetics in vitro.

Middle East Consensus Statement on the Prevention, Diagnosis, and Management of Cow's Milk Protein Allergy

Presented are guidelines for the prevention, diagnosis, and treatment of cows milk protein allergy (CMPA) which is the most common food allergy in infants. It manifests through a variety of symptoms that place a burden on both the infant and their caregivers. The guidelines were formulated by evaluation of existing evidence-based guidelines, literature evidence and expert clinical experience. The guidelines set out practical recommendations and include algorithms for the prevention and treatment of CMPA. For infants at risk of allergy, appropriate prevention diets are suggested. Breastfeeding is the best method for prevention; however, a partially hydrolyzed formula should be used in infants unable to be breastfed. In infants with suspected CMPA, guidelines are presented for the appropriate diagnostic workup and subsequent appropriate elimination diet for treatment. Exclusive breastfeeding and maternal dietary allergen avoidance are the best treatment. In infants not exclusively breastfed, an extensively hydrolyzed formula should be used with amino acid formula recommended if the symptoms are life-threatening or do not resolve after extensively hydrolyzed formula. Adherence to these guidelines should assist healthcare practitioners in optimizing their approach to the management of CMPA and decrease the burden on infants and their caregivers.

A novel mutation in ORAI1 presenting with combined immunodeficiency and residual T-cell function.

Lymphocyte phenotype (normal range) Lymphocyte count (cells/mL)* 7,310 (3,400-9,000) CD3 (cells/mL) 4,553 (1,900-5,900) CD3CD4 3,972 (1,400-4,300) Naive CD3CD4CD45RA 30.1% (50%-85%) Memory CD3CD4CD45RO 69.9% (15%-50%) CD3CD8 516 (500-1,700) Naive CD3CD8CD45RA 65.8% (50%-85%) Memory CD3CD8CD45RO 34.2% (15%-50%) T-cell oligoclonality Not detectable CD19 (cells/mL) 2,159 (610-2,600) IgDCD27 89.6% (65.8%-91.4%) IgDCD27 2.1% (3.6%-18.8%) IgDCD27 4.2% (0.9%-14.1%) CD16/CD56 (cells/mL) 312 (160-950) Immunoglobulins (mg/dL) (normal range) IgG 731 (215-714) IgA 433 (8.1-68) IgM 101 (35-102) IgE 6 (0.44-16.3) Lymphocyte proliferation (cpm) (control§) PHA 128,077 (222,208) Pokeweed mitogen 102,413 (141,446) Concanavalin A 32,560 (64,276) Background 403 (775) Tetanus 8,252 (61,433) Diphtheria 6,543 (54,298) Background 2,310 (4,452) Cytotoxicity studies NK-cell lytic units Not detectable (>3.1) Cytotoxic T-lymphocyte lytic units 1.6 (6)

Prevalence and triggers of allergic rhinitis in the United Arab Emirates

Background and objectivesAllergic rhinitis is a morbid condition that is frequently overlooked by patients and physicians. This type of atopy has not been adequately investigated in the United Arab Emirates.MethodsThis cross-sectional, population-based observational study was conducted in the seven Emirates (Abu Dhabi, Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah). It used the European Community Respiratory Health Survey (ECRHS II) to screen for allergic rhinitis in people living in this region.ResultsSymptoms of allergic rhinitis were present in 85 (7%) of the 1,229 study population. Only 33 (39%) patients received treatment. Seventy-six (89%) patients had asthma. Thirty-seven (44%) patients were poly-sensitized. Symptoms were aggravated by dust (59%), grass/pollens (44%) and proximity to animals (21%). Winter was the peak season (37%), followed by spring (30%), autumn (18%) and summer (15%). Grass/pollen allergies were clustered in the winter, spring and summer (p ≤ 0.001). Dust was non-seasonal (p ≥ 0.121) and animal allergy was worse in the winter (p = 0.024) and spring (p = 0.044). Spring symptoms were less common in people living in the inner city (p = 0.003).ConclusionsAt least 7% of the studied population had allergic rhinitis. Most (71%) of these patients had environmental triggers and remained untreated. Allergic rhinitis awareness and measures to control allergens and dust are needed. The impact of preventing allergic rhinitis on other common atopies in the region deserves future studies.

The Cytotoxicity of Aflatoxin B1 in Human Lymphocytes

OBJECTIVES Aflatoxin B1 (AFB1) is a naturally occurring carcinogenic and immunosuppressive compound. This study was designed to measure its toxic effects on human peripheral blood mononuclear cells (PBMC). METHODS The study recruited 7 healthy volunteers. PBMC were isolated and cellular respiration was monitored using a phosphorescence oxygen analyser. The intracellular caspase activity was measured by the caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin. Phosphatidylserine exposure and membrane permeability to propidium iodide (PI) were measured by flow cytometry. RESULTS Cellular oxygen consumption was inhibited by 2.5 μM and 25 μM of AFB1. Intracellular caspase activity was noted after two hours of incubation with 100 μM of AFB1. The number of Annexin V-positive cells increased as a function of AFB1 concentration and incubation time. At 50 μM, a significant number of cells became necrotic after 24 hours (Annexin V-positive and PI-positive). CONCLUSION The results show AFB1 is toxic to human lymphocytes and that its cytotoxicity is mediated by apoptosis and necrosis.

In vitro biocompatibility of calcined mesoporous silica particles and fetal blood cells

Background: The biocompatibility of two forms of calcined mesoporous silica particles, labeled as MCM41-cal and SBA15-cal, with fetal blood mononuclear cells was assessed in vitro. Methods and results: Fetal mononuclear cells were isolated from umbilical cord blood and exposed to 0.5 mg/mL of MCM41-cal or SBA15-cal for several hours. Transmission electron micrographs confirmed the presence of particles in the cytosol of macrophages, neutrophils, and lymphocytes without noticeable damage to the cellular organelles. The particles (especially MCM41-cal) were in close proximity to plasma, and nuclear and mitochondrial membranes. Biocompatibility was assessed by a functional assay that measured cellular respiration, ie, mitochondrial O2 consumption. The rate of respiration (kc, in μM O2 per minute per 107 cells) for untreated cells was 0.42 ± 0.16 (n = 10), for cells treated with MCM41-cal was 0.39 ± 0.22 (n = 5, P > 0.966) and for cells treated with SBA15-cal was 0.44 ± 0.13 (n = 5, P > 0.981). Conclusion: The results show reasonable biocompatibility of MCM41-cal and SBA15-cal in fetal blood mononuclear cells. Future studies are needed to determine the potential of collecting fetal cells from a fetus or neonate, loading the cells in vitro with therapeutic MCM41-cal or SBA15-cal, and reinfusing them into the fetus or neonate.

Attentiveness of pediatricians to primary immunodeficiency disorders

BackgroundPrimary immunodeficiency (PID) is a cluster of serious disorders that requires special alertness on the part of the medical staff for prompt diagnosis and management of the patient. This study explored PID knowledge and experience among pediatricians of wide educational backgrounds, practicing in the United Arab Emirates (UAE).MethodA self-administered questionnaire was used to determine the competency of pediatricians in their knowledge of PID disorders. This study questionnaire included questions on PID signs and symptoms, syndromes associated with immunodeficiency, screening tests, interpreting laboratory tests and case management. The participants were 263 pediatricians of diverse education working in the 27 governmental hospitals in all regions of UAE.ResultsThe overall performance of the pediatricians did not differ based on their age, gender, origin of certification, rank, or years of experience. Of the 50 questions, 20% of pediatricians answered correctly <60% of the questions, 76% answered correctly 60 to 79% of the questions, and 4% answered correctly ≥80% of the questions. Seventeen of the 19 PID signs and symptoms were identified by 55 to 97%. Four of 5 syndromes associated with immunodeficiency were identified by 50 to 90%. Appropriate screening tests were chosen by 64 to 96%. Attention to the laboratory reference range values as function of patient age was notably limited.ConclusionsThere was a noteworthy deficiency in PID work-up. Therefore, implementing effective educational strategies is needed to improve the competency of pediatricians to diagnose and manage PID disorders.