Chronic inflammatory state in sickle cell anemia patients is associated with HBB*S haplotype

The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB^*S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0 ± 0.6) mg/kg/day for 6–60 (18 ± 3.4) months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with the Bantu/Bantu haplotype and greater levels than those of subjects with the Benin/Benin haplotype. For IL-17, a slight trend toward decreased levels was observed in the subjects with the Benin/Benin haplotype, when compared to those with the Bantu/Bantu and Bantu/Benin haplotypes; however, this difference was not statistically significant. Our results show that genetic polymorphisms in sickle cell anemia are associated with the inflammatory profile.     

Evaluation of Th17 related cytokines associated with clinical and laboratorial parameters in sickle cell anemia patients with leg ulcers

Leg ulcers (LUs) represent one of the main causes of morbidity in sickle cell anemia (SCA). This manifestation has been related to hemolysis, infections predisposition and inflammation that leads cytokines secretion. In this context, our study aimed to evaluate Th17 related cytokines (IL-6, IL-17A, IL-22 and IL-23) in serum and peripheral mononuclear cells culture supernatants with and without lymphoproliferative stimulation (anti-human CD3 and anti-human CD28). The cytokines levels were also correlated to clinical, hematological and biochemical parameters in SCA patients with and without LUs history (SCALU and SCAWH) as well as in healthy controls. In SCALU patients, high levels of IL-17A were associated with absence of acute chest syndrome (ACS, p = 0.0328). The other clinical parameters analyzed (osteonecrosis, stroke, priapism, splenectomy and blood transfusions history) were not significantly related with other cytokine levels. In SCALU patients was also observed that IL-17A increased levels were associated with high levels of LDH (p = 0.0130), the same association pattern was found for IL-6 (0.0160) and IL-22 (p = 0.0165) in the SCALU group. Interestingly, we did not find statistical correlations with these parameters in SCAWH group. The other hematological parameters (hemoglobin, leucocyte and reticulocyte count) and indirect bilirrubin did not show any correlation with analyzed cytokines in both groups. So, for the first time, we show that IL-17A present in SCALU patients may exert a preventive role in the ACS development. Furthermore, IL-6, IL-17A and IL-22 accompanied the LDH levels only in SCALU patients suggesting to serve as additional markers of hemolysis or to be related with immunity response against extracellular pathogens.     

Prevalence of Anemia Among Unselected Adults with Diabetes Mellitus and Normal Serum Creatinine Levels

ObjectiveTo determine the prevalence of anemia in a cohort of patients with diabetes and normal serum creatinine concentration in a primary care clinic.MethodsWe undertook a retrospective cohort study, comparing adult patients who had diabetes, with or without anemia. Patients older than 18 years who had diabetes were identified by using the computerized database for the years 2006 and 2007 in a primary care clinic. Patients with hemoglobin levels < 13.7 g/dL (men < 60 years old), ≤ 13.2 g/dL (men ≥ 60 years old), or < 12.2 g/dL (women) with no known cause of anemia were identified and compared with patients who had diabetes but not anemia. All patients had normal serum creatinine levels (men ≤ 1.5 mg/dL and women ≥ 1.4 mg/dL).ResultsOf 594 eligible patients with diabetes, 192 (32%) had anemia. Older age, higher serum urea and creatinine levels, lower estimated glomerular filtration rates, and reduced serum iron levels were more common in the patients with diabetes who had anemia than in those without anemia. The prevalence of anemia was higher in patients treated with “glitazones,” insulin, and angiotensin receptor blockers in comparison with those receiving other orally administered hypoglycemic medications. In stepwise logistic regression analysis, only serum creatinine, age, and use of glitazones retained statistical significance.ConclusionIn a community clinic, the prevalence of anemia in unselected patients with diabetes and normal serum creatinine levels was 32%. Factors associated with anemia were older age, higher serum creatinine levels, and use of glitazone therapy. (Endocr Pract. 2009;15:714-719)     

Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke

IntroductionStroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population.MethodsIn this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs (SORT1-rs646218 and OLR1-rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results.ResultsThe rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR’s) and Multiple logistic regression analysis (p < 0.05). Correlation between lipid profile and genotypes has confirmed the significant relation between triglycerides and rs646218 and rs1105364 6polymorphisms. However, rs11053646 polymorphism was correlated with HDLC (p = 0.04). Genotypes were examined in both males' vs. males and females' vs. females in cases and control and we concluded that in rs11053646 polymorphisms with male subjects compared between cases and controls found to be associated with dominant model heterozygote genotypes (p < 0.05).ConclusionThe results of the current study confirmed the SORT1 and OLR1 SNPs were associated in the Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.     

Tolerability and toxicity of prophylactic cranial irradiation in patients with non-small cell lung cancer – Results of a phase II study (with estimation of hematological toxicity,pituitary function and magnetic resonance spectra changes)

AimTo evaluate the tolerability and toxicity of PCI in patients with NSCLC.BackgroundProphylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment.Materials and methodsFrom 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30 Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with ¹H nuclear magnetic resonance spectra, and estimation of pituitary function.ResultsDuring follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease (p = 0.062). Visual-motor function deteriorated after treatment (p < 0.059). Performance IQ decreased (p < 0.025) and the difference between performance IQ and verbal IQ increased (p < 0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI.ConclusionPCI in the current series was well tolerated and associated with a relatively low toxicity.     

Hematological and biochemical investigations on the effect of vitamin E and C on Oreochromis niloticus exposed to zinc oxide nanoparticles

This study was carried out to determine the LC₅₀ of zinc oxide nanoparticles (ZnONPs) on Oreochromis niloticus and to investigate the effect of vitamin E and C on hematological and biochemical alterations induced by two sublethal concentrations (1 and 2 mg/L) of ZnONPs. One hundred and eighty fish were used for studying the lethal concentrations of ZnONPs. For sublethal study two hundred and twenty-five males of O. niloticus were equally divided into five groups, control, the second and the third were treated with 1 and 2 mg/L ZnONPs respectively. The fourth and fifth were exposed to the same concentrations of ZnONPs plus vitamins E and C. The results revealed that the 96 h LC₅₀ of ZnONPs was 3.1 ± 0.4 mg/L. The sublethal study revealed the presence of normocytic normochromic anemia in groups (2, 3 and 5) along the experiment period. The 4th group showed normocytic normochromic anemia at the 7th day and microcytic hypochromic anemia at the 15th day. Leukocytosis, heterophilia, lymphopenia and monocytopenia were recorded at the 7th day in all treated groups compared with the normal control. At the 15th day heteropenia, lymphopenia and monocytopenia were reported in all treated groups. A significant increase in the serum levels of alkaline phosphatase, aminotransferases, urea, creatinine and erythrocytic nuclear and morphological abnormalities along the experimental periods in all treated groups compared with the normal control. Serum total protein and albumin levels were significantly decreased at the same period in the same groups. Addition of vitamin E and C to the diet (groups 4 and 5) significantly improved all measured parameters compared with groups (2 and 3) which treated with ZnONPs only.     

Characterizing Glucose Changes Antecedent to Hypoglycemic Events in the Intensive Care Unit

ObjectiveTo determine whether patterns of glucose changes before hypoglycemia vary according to the severity of the event.MethodsIn this retrospective analysis, point-ofcare blood glucose (POC-BG) data were obtained from the intensive care units (ICUs) of a convenience sample of hospitals that responded to a survey on inpatient diabetes management quality improvement initiatives. To evaluate POC-BG levels before hypoglycemic events, data from patients who experienced hypoglycemia during their time in the ICU were examined, and their glucose changes were assessed against a comparison group of patients who achieved a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia. Absolute glucose decrease, glucose rate of change, and glucose variability before hypoglycemic events (< 40, 40-49, 50-59, and 60-69 mg/ dL) were calculated.ResultsA total of 128 419 POC-BG measurements from 2942 patients in 89 ICUs were analyzed. Patients who experienced the most severe hypoglycemic episodes had the largest absolute drop in their glucose levels before the event (P < .001). The glucose rate of change before a hypoglycemic event increased with worsening hypoglycemia: mean (± standard deviation) glucose rate of change was-1.69 (± 2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, -0.56 (± 2.65) mg/dL per min before an episode with glucose values 60 to 69 mg/dL, but only -0.39 (± 0.70) for patients who attained a glucose range of 80 to 110 mg/dL without hypoglycemia (P < .001). Glucose variability before an event progressively increased with worsening biochemical hypoglycemia and was least among patients achieving glucose concentrations in the 80 to 110-mg/dL range without hypoglycemia (P < .001).ConclusionsAntecedent glucose change and variability were greater for patients who experienced hypoglycemia. If monitored, these patterns could potentially alert clinicians and help them take preventive measures. Further examination of how these parameters interact with other predisposing risk factors for hypoglycemia is warranted. (Endocr Pract. 2012;18:317-324)     

The use of transgenic mouse models to reveal the functions of Ca2 + buffer proteins in excitable cells

BackgroundCytosolic Ca^2 + buffers are members of the large family of Ca^2 +-binding proteins and are essential components of the Ca^2 + signaling toolkit implicated in the precise regulation of intracellular Ca^2 + signals. Their physiological role in excitable cells has been investigated in vivo by analyzing the phenotype of mice either lacking one of the Ca^2 + buffers or mice with ectopic expression.Scope of ReviewIn this review, results obtained with knockout mice for the three most prominent Ca^2 + buffers, parvalbumin, calbindin-D28k and calretinin are summarized.Major ConclusionsThe absence of Ca^2 + buffers in specific neuron subpopulations, and for parvalbumin additionally in fast-twitch muscles, leads to Ca^2 + buffer-specific changes in intracellular Ca^2 + signals. This affects the excitation–contraction cycle in parvalbumin-deficient muscles, and in Ca^2 + buffer-deficient neurons, properties associated with synaptic transmission (e.g. short-term modulation), excitability and network oscillations are altered. These findings have not only resulted in a better understanding of the physiological function of Ca^2 + buffers, but have revealed that the absence of Ca^2 + signaling toolkit components leads to protein-and neuron-specific adaptive/homeostatic changes that also include changes in neuron morphology (e.g. altered spine morphology, changes in mitochondria content) and network properties.General SignificanceThe complex phenotype of Ca^2 + buffer knockout mice arises from the direct effect of these proteins on Ca^2 + signaling and moreover from the homeostatic mechanisms induced in these mice. For a better mechanistic understanding of neurological diseases linked to disturbed/altered Ca^2 + signaling, a global view on Ca^2 + signaling is expected to lead to new avenues for specific therapies. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.     

Segmentation d’images de lésions cérébrales primitives en TEP FET : influence du volume de travail

Purpose(1) Evaluate the reproducibility of segmentation methods depending on the preselection region for tumour volume determination on ¹⁸F-fluoro-ethyl-tyrosine (FET) PET. (2) Evaluate the intra and inter-operator reproducibility of the manual delineation. (3) Compare this delineation with the segmentation methods.Materials and methodsEighteen FET PET of patients with glioblastoma were analysed. Preselection regions were determined prior to any segmentation. Two physicians delineated the tumour volume manually. The tumour volume was also delineated with a threshold method (40 and 70% of SUV_max), and a random walk based method. Pearson coefficient (r) (P < 0.05 for r > 0.468) and Jaccard indices (JI) were used to compare the volumes.ResultsManual delineation was reproducible with r = 0.97 and IJ = 0.65 for intra-operator, and r = 0.76 and IJ = 0.45 for inter-operator reproducibility. The preselection regions for a given lesion were different and the segmentation varied with the preselection region: r = 0.55 JI = 0.58; r = 0.85 JI = 0.83; r = 0.70 JI = 0.39 respectively for the threshold of 40%, 70% and the random walk. The segmentation differed form de manual delineation with r = 0.37 and JI = 0.16; r = 0.54 and JI = 0.42; r = 0.43 and JI = 0.37 respectively for the threshold of 40%, 70% and the random walk.ConclusionThe reproducibility of the segmentation methods depends extensively on the preselection region. The intra-operator reproducibility of cerebral lesion delineation on FET PET is satisfactory. The inter-operator reproducibility could be improved.     

CYP1A2 genetic polymorphisms and adenocarcinoma lung cancer risk in the Tunisian population

AimsIn this study, the effects of four single nucleotide polymorphisms (SNPs), ? 3860G > A, ? 2467delT, ? 739T > G and ? 163C > A, of CYP1A2 gene on lung cancer were evaluated in Tunisian population.Main methodsFour polymorphisms of CYP1A2 gene were analysed in 109 healthy smokers and in 101 lung cancer cases, including 63 with squamous cell carcinoma (SCC) and 41 with adenocarcinoma (AD). The genotyping for the SNPs ? 3860 G > A, ? 2467delT, ? 739T > G and ? 163C > A was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis.Key findingsThe results showed that smokers with CYP1A2 gene polymorphisms were associated with an increased risk for the development of lung AD. There was however no significant increased risk of developing lung SCC in smokers having CYP1A2 gene polymorphisms. An increased risk of developing AD was observed in smokers who are carriers of at least one copy of ? 3680A or ? 739G giving a significant odds ratio (OR) of 6.02 (CI = 2.91–12.9) and 3.01 (CI = 1.54–5.98), respectively.SignificanceThese genotyping data are consistent with the hypothesis that tobacco-specific-N-nitrosamines (TSN) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major contributors to the development of lung AD and that CYP1A2 gene product plays an important role in the metabolic activation of NNK. This study suggests that SNPs of CYP1A2 could be considered as promising biomarkers in the aetiology of lung AD in smokers.     

Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin

AimsThis study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties.Main methodsAPOE null mice at 6 and 15 weeks of age were treated with melatonin at a dose of 0.1 mg/kg/day or 10 mg/kg/day. We evaluated both histopathological alterations in endothelial and vascular smooth muscle cells by CyPA and rolling mononuclear cell expression during the early phase of atherosclerosis development.Key findingsOur study showed that CyPA expression increases and may modulate inflammatory cell adhesion and interleukin-6 expression inducing vascular smooth muscle cell migration and inflammatory cell extravasation in a time-dependent manner. Moreover, we observed an indirect atheroprotective effect of melatonin on vascular injury; it inhibited CyPA mediated inflammatory cell extravasation and oxidative stress.SignificanceThe melatonin treatment may represent a new atheroprotective approach that contributes to reducing the early phase of atherosclerosis involving the rolling of monocytes, their passage to subendothelial space and inhibition of CyPA expression.     

Évaluation par la TEMP–TDM des lésions classées indéterminées en scintigraphie osseuse chez les patients de cancérologie

The aim of the present study was to investigate the contribution of the single photon emission computed tomography/computed tomography (SPECT/CT) in cancer patients and to evaluate its ability to correctly classify indeterminate lesions on planar bone scintigraphy (PBS).MethodsFrom November 2006 to August 2007, all patients with confirmed malignancy, whose PBS showed indeterminate lesions, underwent without delay a SPECT/CT. The study included 120 patients (67 men, 53 women), with a mean age of 69 ± 12 years (range 42–96 years). The patients with obvious metastases, important pains or who did not accept the examination were excluded from the study. The location of the lesions was described either as precise, probable or indeterminate. The lesions were classified either as definitely malignant, definitely benign or indeterminate.ResultsBreast, prostate, lung and kidney neoplasms represented approximately 80% of all cancers. The PBS highlighted 267 lesions of location either as precise (n = 29), probable (n = 129) or indeterminate (n = 109), classified either as definitely malignant (n = 28), definitely benign (n = 27) or indeterminate (n = 212). The SPECT/CT revealed 440 lesions, of location either as precise (n = 353), likely (n = 39) or indeterminate (n = 48), classified either as definitely malignant (n = 84), definitely benign (n = 305) or indeterminate (n = 51). Thoracic and lumbar spine and pelvis were the locations of 79% of the scintigraphic lesions and of 88% of the osseous metastases. SPECT/CT modified the final report of 80 patients, by excluding from metastases (n = 2), by showing metastases (n = 23) and by showing the benign character of indeterminate lesions (n = 55). Moreover, 69 patients out of 120 (> 57%) had an evolution confirmed with 35 true positives, 31 true negatives, one false negative and two patients with indeterminate lesions on SPECT/CT, without osseous metastasis.ConclusionThe assessment of the indeterminate scintigraphic lesions of oncologic patients benefits from the SPECT/CT. The lesion-based analysis showed that the SPECT/CT detected more lesions (+64%) and correctly classified 88% of the detected lesions. The patient-based analysis highlighted that SPECT/CT modified the final report for more than 66% of the patients. The follow-up showed that SPECT/CT correctly classified for more than 95% of the patients.     

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

IntroductionObesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD).Methods22 severe obese subjects (Median Body Mass Index (BMI): 44.5 kg/m²) were included in a dietary intervention study of 6 month, consisting of a very low calorie formula diet phase (VLCD: 800 kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR).ResultsMean body weight reduction by VLCD accounted to 21.7 kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (r_S = −0.642, p = 0.001) and HOMA (r_S = −0.419, p = 0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p = 0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p = 0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (r_S = −0.650, p = 0.022) during intervention.ConclusionAnti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.     

CHEK2 gene alterations in the forkhead-associated domain, 1100delC and del5395 do not modify the risk of sporadic pancreatic cancer

Checkpoint kinase 2 gene (CHEK2) alterations increase risk of several cancer types. We analyzed selected CHEK2 alterations in 270 Czech pancreatic cancer patients and in 683 healthy controls. The pancreatic cancer risk was higher in individuals who inherited rare alterations in CHEK2 region involving forkhead-associated domain other than I157T (OR = 5.14; 95% CI = 0.94–28.23) but the observed association was non-significant (p = 0.057). The most frequent I157T mutation did not alter the pancreatic cancer risk and neither the followed deletion of 5395 bp nor c.1100delC were found in any of pancreatic cases. We conclude that the I157T, other alterations in its proximity, del5395 and c.1100delC in CHEK2 do not predispose to pancreatic cancer risk in the Czech population.     

Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa

BackgroundThe Eastern Cape Province of South Africa, which includes the former Transkei has high rates of squamous cell oesophageal cancer (OC), thought to be caused mainly by nutritional deficiencies and fungal contamination of staple maize. A hospital-based case-control study was conducted at three of the major referral hospitals in this region to measure, among other suspected risk factors, the relative importance of tobacco smoking and alcohol consumption for the disease in this population.MethodsIncident cases (n = 670) of OC and controls (n = 1188) were interviewed using a structured questionnaire which included questions on tobacco and alcohol-related consumption. Odds ratios (ORs) with 95% confidence intervals for each of the risk factors were calculated using unconditional multiple logistic regression models.ResultsA monotonic dose-response was observed across the categories of each tobacco-related variable in both sexes. Males and females currently smoking a total of >14 g of tobacco per day were observed to have over 4-times the odds of developing OC (males OR = 4.36, 95% CI 2.24–8.48; females OR = 4.56, 95% CI 1.46–14.30), with pipe smoking showing the strongest effect. Similar trends were observed for the alcohol-related variables. The quantity of ethanol consumed was the most important factor in OC development rather than any individual type of alcoholic beverage, especially in smokers. Males and females consuming >53 g of ethanol per day had approximately 5-times greater odds in comparison to non-drinkers (males OR = 4.72, 95% CI 2.64–8.41; females OR = 5.24, 95% CI 3.34–8.23) and 8.5 greater odds in those who smoked >14 g tobacco daily. The attributable fractions for smoking and alcohol consumption were 58% and 48% respectively, 64% for both factors combined.ConclusionTobacco and alcohol use are major risk factors for OC development in this region.ImpactThis study provides evidence for further reinforcement of cessation of smoking and alcohol consumption to curb OC development.     

Effects of l-glutamine supplementation alone or with antioxidants on hydrogen peroxide-induced injury in human intestinal epithelial cells

Background and aimsIn situations of oxidative stress, l-glutamine (Gln) exhibits protective effects which may be potentiated by its combination with antioxidants. The aim of this study was to compare the effects of a Gln-antioxidants formula vs Gln alone in intestinal epithelial cell lines Caco-2 and HCT-8 submitted to hydrogen peroxide-induced oxidative injury.MethodsCells were cultured during 24 h with 0, 1, 2, 4, 8 or 16 mM Gln or isomolar Gln combined to cysteine, vitamine C, vitamine E, β-carotene, Zn and Se (Gln-AOX). After 24 h, membrane integrity was assessed by means of LDH leakage, the level of oxidative stress by analysis of 8-isoprostane concentration and cell viability by colorimetric-MTT assay.ResultsLDH activity decreased (P < 0,05) with a dose-dependent manner in both cell types with Gln-AOX whereas Gln decreased LDH release only in the Caco-2 line at 1 mM. For both cell lines, release of 8-isoprostane was not blunted by any treatment and increased paradoxically with 16 mM Gln (P < 0.05). Cell viability was higher (P < 0.05) using Gln-AOX vs Gln at 4, 8 and 16 mM in both cell lines.ConclusionsThese results suggest that Gln-AOX is more efficient than Gln alone to preserve cell membrane integrity and viability in intestinal cell lines submitted to oxidative injury.     

Exogenous and endogenous stages of Eimeria perforans naturally infected domestic rabbit (Oryctolagus cuniculus) in Saudi Arabia: Light microscopic study

Exogenous and endogenous stages of Eimeria perforans naturally infected rabbits in Saudi Arabia were described. The prevalence of infection was 75%. Oocysts were ovoid to elliptical and measured 16 × 10 μm. The four dizoic sporocysts were ovoid and measured 7 × 5 μm. Endogenous stages were restricted to the duodenum. Meronts, microgamonts, macrogamonts and young oocysts were recorded and described.     

Influence of premolar extraction or non-extraction orthodontic therapy on the angular changes of mandibular third molars

AimTo compare the angular changes of the third molars relative to the occlusal plane and to the second molar long axis in extraction group and compare these changes with a non extraction group.Materials and methodsThe study included pre and post treatment panoramic radiograph records of 90 subjects treated by first premolar extractions and 90 subjects who had been treated with non extraction orthodontic therapy (n = 90). Two angular variables were measured. Firstly, the angle between the long axis of the third molar and the occlusal plane (M3–OP) and secondly, the angle between the long axis of the third molar and the long axis of the second molar (M3–M2). Data were analyzed by paired and student’s t-test.ResultThe analyzed data to assess the changes in the third molar angulation from pretreatment to post treatment did not vary significantly in both the groups (p < 0.05). Both the groups showed decreased angular values. The M3–OP angular difference was (−7.3 ± 2.45) in extraction group as compared to (−5.85 ± 1.77) in non extraction group. The M3–M2 angular difference of (−4.26 ± 3.11) in extraction group and (−2.98 ± 1.74) in non-extraction group was observed.ConclusionExtraction of premolars did not demonstrate considerable changes on the angulation of the third molars. The factors other than premolar extractions may influence the angulation of the third molars.