Post-transplant cyclophosphamide and bortezomib inhibit dendritic cell maturation and function and alter their IκB and NFκB

Impairing dendritic cell (DC) function to prevent graft versus host disease (GvHD) is an appealing concept. DC antigen presentation is NF-κB pathway-dependent and bortezomib might therefore play a role in preventing alloreactivity. We obtained DC from the blood of patients enrolled in a phase I study using post-transplant cyclophosphamide and bortezomib for prevention of GvHD. Control samples were obtained from patients receiving standard GvHD prevention regimen. Pre-treatment samples were also collected from enrolled patients. DC isolated on days + 1, + 4, and + 7 showed progressive decrease in the expression of maturation markers in comparison to control. In a DC–CD4 + mixed lymphocyte reaction (MLR) where DC isolated from the recipient blood before graft infusion were the stimulator cells, T cell proliferation measured by bromodeoxyuridine (BrdU) integration was decreased in samples obtained on days + 14 and + 21 in comparison to control group. Finally, measured by real-time PCR, the expression of IκB progressively increased while the expression of NF-κB decreased in DC on days + 1, + 4, and + 7, in comparison to pre-treatment paired controls. We conclude that our data further justify exploring the role of bortezomib in GvHD prevention and propose a novel mechanism of action of bortezomib in DC.     

Prevalence and risk factors of parasitic diseases among Saudi children: An updated review

Intestinal parasite infection (IPI) is a declining global health problem. However, in certain parts of the world, the misconception that certain diseases are avoided owing to the existence of prevention strategies, medication and the frequency of awareness campaigns remains underestimated. Recent studies in Saudi Arabia have reported high prevalence rates for IPI; however, the prevalence in Saudi Arabia varies from city to city and from age group to age group. Moreover, the most prevalent causative species vary in different areas of Saudi Arabia due to differences in the characteristics of emerging populations. The prevalence of IPI has also been correlated with multiple risk factors, such as age, gender, health awareness, health habits and socioeconomic status. Therefore, more attention should be given to IPIs in Saudi Arabia and the risk factors should be better addressed to monitor and reduce the spread of parasite infections, particularly among younger children.     

Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease

AIM:To study the association of apolipoprotein E(APOE) polymorphisms with the susceptibility ofinflammatory bowel disease(IBD) in Saudi patients.METHODS:APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis(n = 84) or Crohn's disease(n = 94) and matched controls(n = 200) using polymerase chain reaction and reverse-hybridization techniques.RESULTS:The frequencies of the APOE ε2 allele and ε2/ε3 and ε2/ε4 genotypes were significantly higher in IBD patients than in controls(P 0.05),suggesting that the ε2 allele and its heterozygous genotypes may increase the susceptibility to IBD.On the contrary,the frequencies of the ε3 allele and ε3/ε3 genotype were lower in IBD patients as compared to controls,suggesting a protective effect of APOE ε3 for IBD.The prevalence of the ε4 allele was also higher in the patient group compared to controls,suggesting that the ε4 allele may also increase the risk of IBD.Our results also indicated that the APOE ε4 allele was associated with an early age of IBD onset.No effect of gender or type of IBD(familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study.CONCLUSION:APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients,though further studies with a large-size population are warranted.     

Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)

ABSTRACT: BACKGROUND: Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the "NCD" and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions. Materials and methods Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation. RESULTS: NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver. CONCLUSION: The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin.     

Possession by 'Jinn' as a cause of epilepsy (Saraa): a study from Saudi Arabia

PurposeEpilepsy has been linked to divine, demonic and supernatural powers throughout its long history.This study was conducted to explore if misconceptions such as possession by demons (Jinns) are still believed to be a cause of epilepsy among educated Saudis today.MethodThis study was conducted among university-educated school teachers and undergraduate students. The findings are based on a structured questionnaire enquiring about familiarity with epilepsy, sources of knowledge, and depth of knowledge about specific aspects of epilepsy.ResultsResponses from 398 participants were included in the analysis of the results. Most participants had witnessed epileptic seizures. 2/3 of the participants reported that they had learned about epilepsy from friends and relatives. 172 (43.1%) members believed that epilepsy is a psychiatric disease. 62 (40.3%) of the school teachers and 123 (50.4%) of the students in the study considered possession as a cause of epilepsy. The majority of the cohort believed medical treatment for the condition exists despite the fact that a significant number believed that faith healers and traditional medicine can be of help in the treatment of epilepsy.ConclusionJinn possession is still believed to be a cause of epilepsy in Saudi society, even among fairly well-educated people. This finding emphasizes the urgent need for public education campaigns at all levels of education.     

Effect of fire smoke on some biochemical parameters in firefighters of Saudi Arabia

Background

Lead exposure is common in automobile battery manufacture and repair, radiator repair, secondary smelters and welding units. Urinary Aminolevulinic acid has validity as a surrogate measure of blood lead level among workers occupationally exposed to lead. This study had therefore assessed the magnitude of lead exposure in battery repair workers of three transport service enterprises.

Methods

To this effect, a cross-sectional study was carried out on lead exposure among storage battery repair workers between November 2004 and May 2005 from Anbasa, Comet and Walia transport service enterprises, Addis Ababa, Ethiopia. Subjective information from the workers was obtained by making use of structured questionnaire. Other information was obtained from walkthrough evaluation of the repair units. Aminolevulinic acid levels in urine were used as an index of the exposure. This was coupled to measurements of other relevant parameters in blood and urine collected from adult subjects working in the repair units as well as age matched control subjects that were not occupationally exposed to lead. Aminolevulinic acid was determined by spectrophotometry, while creatinine clearance, serum creatinine, urea and uric acid levels were determined using AMS Autolab analyzer.

Results

Urinary aminolevulinic acid levels were found to be significantly higher in exposed group (16 μg/ml ± 2.0) compared to the non-exposed ones (7 μg/ml ± 1.0) (p < 0.001). Alcohol taking exposed subjects exhibited a significant increase in urinary aminolevulinic acid levels than non-alcohol taking ones (p < 0.05). Moreover, urinary aminolevulinic acid levels of exposed subjects increased with age (p < 0.001) as well as duration of employment (p < 0.001). Whereas serum uric acid levels of exposed subjects was significantly higher than non-exposed ones (p < 0.05), no statistically significant difference had been found in renal indices and other measured parameters between exposed and non-exposed subjects. From the questionnaire responses and walkthrough observations, it was also known that all the repair units did not implement effective preventive and control measures for workplace lead exposure.

Conclusion

Taken together, these findings indicated that workers in lead acid battery repair units of the transport service enterprises are not protected from possibly high lead exposure. Thus, strict enforcement of appropriate and cost effective preventive and control measures is required by all the enterprises.     

Acute Renal Failure in the State of Qatar: Presentation and Outcome

Despite major improvements in health care, acute renal failure is still one of the main prognostic factors in terms of patient mortality and long-term morbidity. This cohort prospective study to evaluate the patterns and outcomes of renal failure in Qatar was performed between January and June 2005. Of the 213 patients followed prospectively from referral to the end of their hospitalization, 66.7% were males and 33.3% females. Their overall mean age was 60 years; the majority were referred from critical care units. Comorbidity was present in 87% of all patients. Volume depletion, hypotension, and sepsis were the main predisposing factors for renal failure. Eighty three patients (39%) needed renal replacement treatment and 130 (61%) were treated conservatively. The majority of critical care patients needed dialysis. Overall mortality was 23.9%, 7% needed chronic dialysis, and 69.1% were discharged with normal or mild renal impairment. This study showed that acute renal failure was a major factor affecting patient mortality in Qatar. Early treatment of predisposing factors may improve overall patient outcomes.