Human platelet antigen 1, 2 and 5 gene polymorphisms in Egyptians and their potential association with susceptibility to immune thrombocytopenic purpura in Egyptian patients

Objectives: This study determined the incidence of HPA1, HPA2 and HPA5 polymorphisms in 120 Egyptian immune thrombocytopenic purpura (ITP) patients and 120 healthy Egyptian subjects.

Methods: Human platelet antigen (HPA) genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism.

Results: The frequency of HPA1 allele a and b was 78.75 and 21.25% in controls, 80.8 and 19.2% in ITP, respectively. HPA2 allele a and b frequency was 86.25 and 13.75% in controls and of 74.6 and 25.4% in patients, respectively. HPA5 allele a and b frequency was 87.5 and 12.5% in controls, in patients it was 85 and 15%, respectively. With the exception of HPA2, no other significant difference was encountered in HPA allele frequency between controls and ITP patients.

Discussion: Egyptian HPA profile is closely linked to Middle East and neighboring Arabs. The current study noted that in all the studied HPA systems 1, 2 and 5, the ‘a’ allele is more prevalent than the b allele; the most frequent genotype was the homozygous a/a genotype. HPA2b frequency, homo- and hetero-zygous HPA2b genotype frequencies were significantly higher in ITP patients compared to controls.

Conclusion: HPA 2b are 2.37 times more likely to develop ITP compared to those without this allele. The relatively high allele frequency of the HPA-1b in the Egyptian population suggests that this ethnic group has a higher risk of alloimmunization.     

Involvement of Mrp2 (Abcc2) in biliary excretion of moxifloxacin and its metabolites in the isolated perfused rat liver

Moxifloxacin is a novel antibacterial agent that undergoes extensive metabolism in the liver to the glucuronide M1 and the sulfate M2, which are eliminated via the bile. To investigate the role of the multidrug resistance-associated protein (Mrp2) as the hepatic transport system for moxifloxacin and its conjugates, livers of Wistar and Mrp2-deficient TR- rats were perfused with moxifloxacin (10 microM) in a single-pass system. Values for the hepatic extraction ratio (E) and clearance (Cl) were insignificantly higher in TR- rats than Wistar rats (0.193+/-0.050 vs 0.245+/-0.050 for E; 6.85+/-1.96 vs 8.73+/-1.82 mL min(-1) for Cl), whereas biliary excretion and efflux into perfusate over 60 min were significantly lower in the mutant rat strain. Cumulative biliary excretion of M1, M2 and moxifloxacin was significantly reduced to 0.027%, 19.1%, and 29.6% in the TR- rats compared with Wistar rats, indicating that the biliary elimination of M1 is mediated exclusively by Mrp2, whereas that of M2 and moxifloxacin seems to depend mostly on Mrp2 and, to a smaller extent, a further unidentified canalicular transporter. Moxifloxacin stimulates bile flow by up to 11% in Wistar rats, but not in TR- rats, further supporting an efficient transport of this drug and its glucuronidated and sulfated metabolites by Mrp2. Moxifloxacin (10 microM) also reversibly inhibited the Mrp2-mediated biliary elimination of bromsulphthalein in Wistar rats by 34%, indicating competition with the elimination of Mrp2-specific substrates. In conclusion, we found that Mrp2 mediates the biliary elimination of moxifloxacin and its glucuronidated and sulfated metabolites in rats. MRP2 may therefore play a key role in the transport of moxifloxacin and its conjugates into bile in humans.     

Therapeutic properties in Tunisian hot springs: first evidence of phenolic compounds in the cyanobacterium <Emphasis Type="Italic">Leptolyngbya</Emphasis> sp. biomass,capsular polysaccharides and releasing polysaccharides

Background

In Tunisia, the use of hot spring waters for both health and recreation is a tradition dating back to Roman times. In fact, thermal baths, usually called “Hammam” are recommended as a therapeutic and prophylactic measure against many types of illness and toxicity. While the chemical concentration of thermal water is admittedly associated with its therapeutic effects, the inclusion in spa waters of efficient bioproduct additives produced by photosynthetic microorganisms and that act against oxidative stress may comprise a significant supplementary value for thermal centers. The aim of this study was to investigate the antioxidant potential of the Tunisian thermophilic cyanobacterium Leptolyngbya sp. and to determine its phytochemical constituents and phenolic profile.

Methods

BME (Biomass Methanolic Extract), CME (Capsular polysaccharides Methanolic Extract) and RME (Releasing polysaccharides Methanolic Extract) of Leptolyngbya sp. were examined for their antioxidant activities by means of DPPH, hydroxyl radical scavenging and ferrous ion chelating assays. Their total phenols, flavonoids, carotenoids, Mycosporine-like amino acids (MAAs) and vitamin C contents, as well as their phenolic profiles were also determined.

Results

BME has the highest content of phenols (139?±?1.2 mg/g), flavonoids (34.9?±?0.32 mg CEQ/g), carotenoids (2.03?±?0.56 mg/g) and vitamin C (15.7?±?1.55 mg/g), while the highest MAAs content (0.42?±?0.03 mg/g) was observed in CME. BME presented both the highest DPPH and hydroxyl radical scavenging ability with an IC₅₀ of 0.07 and 0.38 mg/ml, respectively. The highest ferrous chelating capacity was detected in CME with an IC₅₀?=?0.59 mg/ml. Phenolic profiles revealed the presence of 25 phenolic compounds with the existence of hydroxytyrosol, oleuropein, resveratrol and pinoresinol.

Conclusion

The study demonstrated that the cyanobacterium Leptolyngbya sp. possesses abundant natural antioxidant products which may have prophylactic and therapeutic effects on many types of illness and toxicity. The present findings not only explain and reinforce the rationale behind traditional therapeutic practices in Tunisia in the exploitation of the country’s hot springs, but support the addition of Leptolyngbya to thermal waters as a means to enhance the value and reputation of the curative nature of Tunisian thermal waters.

     

The many faces of peroxisomal disorders: Lessons from a large Arab cohort

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the “gold standard” very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases.     

Bactériémies à bactéries multirésistantes chez les greffés de cellules souches-hématopoïétiques

Background:

Bacteremia become fearsome in hematopoietic stem cell transplant (HSCT) recipients with the emergence of multidrug-resistant (MDR) strains.

Aim:

Our purpose was to investigate the prevalence of MDR bacteremia in HSCT recipients at the Tunisian National Bone Marrow Transplant Center, associated factors and attributable mortality rate.

Methods:

Our retrospective study (January 2010-December 2017) included all MDR bacteremia in the Hematology department. MDR rods were: extended spectrum beta-lactamase producing Enterobacterales (ESBL-E), P. aeruginosa and A. baumannii resistant to at least three families of antibiotics, methicillin-resistant S. aureus (MRSA) and vancomycin resistant E. faecium (VRE).

Results:

The prevalence of MDR bacteremia among HSCT recipients was 5.9% (48/816) with a stable trend over time (rs=0.18). Neutropenia, prior hospitalization, prior antibiotherapy and prior colonization with MDR pathogens were observed in 59%, 58%, 48% and 31% of cases, respectively. Imipenem was the most prescribed first-line antibiotic (50%). The attributable mortality rate was 13%. MDR bacteria (n=48) belonged to ESBL-E (60%), P. aeruginosa (19%), A. baumannii (13%), MRSA (4%) and VRE (4%). For ESBL-E and P. aeruginosa, the rates of antibiotic resistance were respectively, 17% and 44% to imipenem, 31% and 56% to amikacin and 15% and 0% to colistin. Strains of A. baumannii were susceptible only to colistin. The MRSA (n=2) were resistant to ciprofloxacin and gentamicin and susceptible to glycopeptides. The VRE (n=2) were susceptible to linezolid and tigecycline.

Conclusion:

Low prevalence of MDR bacteremia in HSCT recipients but high attributable mortality rate, requiring reinforcement of hygiene measures.     

Chances of Renal Recovery or Liver Transplantation After Hospitalization for Alcoholic Liver Disease Requiring Dialysis

Digestive Diseases and Sciences - Acute kidney injury in the setting of alcoholic liver disease portends a poor prognosis without liver transplant. Using a tertiary care population, we aimed to...     

Markers of endothelial dysfunction and leucocyte activation in Saudi and non-Saudi haplotypes of sickle cell disease

Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling. Studies are underway to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCD patients.     

Comparative study of palatal rugae shape in two samples of Egyptian and Saudi children

This study was performed to investigate differences in the shape of the individual palatal rugae in two population samples of Arabian children from Egypt and Saudi Arabia, and develop discriminant function to identify the populations based on rugae shape. A total of 152 stone casts (80 from Egyptian and 72 from Saudi children), equally distributed between genders aged 6–8 years were examined for rugae shape (straight, wavy, curved, circular, unification and cross-link) and their incidence was recorded. Association between rugae shape and gender as well as rugae shape and population were tested using chi-square and discriminant function analyses using SPSS 13 statistical package. Curved and wavy were the most prevalent rugae shape in both groups, followed by straight rugae. Circular, converged and diverged unifications were few in number, while cross-link rugae were not observed in Saudi children. No significant gender differences were observed. Chi-square analysis for association between rugae shape and population groups showed significant differences in curved, wavy, cross-link, converged and diverged unification. Three rugae shapes; wavy, diverging unification and cross-link contributed to the discriminant function which enabled population identification. It was concluded that palatal rugae shape revealed significant differences between the two Egyptian and Saudi populations and also confirmed previous reports of lack of gender dimorphism. Discriminant function analysis allowed differentiation of the populations and it is inferred that discrete variables such as rugae shape are better suited for that purpose than continuous variables such as rugae length.