Genetic variation within and among five natural populations of endangered Sclerocarya birrea (A. Rich) subsp. Birrea in Sudan

Knowledge of genetic diversity is important for successful conservation and domestication of species. In order to determine genetic diversity within and among Sclerocarya birrea (A. Rich.) Htochst. subsp. birrea populations in Sudan, random amplified polymorphic DNA (RAPD) markers were used. Leaf materials from 75 seedlings from five populations (Rashad, Alfaid, Alkhwi, Aldamazin and Baw) of this species were used to compare the genetic diversity. A total of 37 bands were generated using four primers. Genetic variation within the populations as estimated by Shannon information index ranged from 0.343 to 0.272 with an overall diversity of 0.306. Analysis of molecular variance revealed that 46% of the variation was attributed to differences among the populations and 54% within the populations (P < 0.001). The gene flow among population was small (Nm = 0.297). UPGMA cluster and principal coordinate analyses (PCA) indicated Alfaid as the most distinct population. Since genetic variation was found to occur among and within the populations of S. birrea (A. Rich.) Hochst. Subsp. birrea, conservation of these populations would help in the maintenance of the species.Key words: Sclerocarya birrea subsp. birrea, genetic variation, conservation, random amplified polymorphicDNA (RAPD), Sudan

Possible association of interleukin-1beta (-511C/T) and interleukin-6 (-174G/C) gene polymorphisms with atherosclerosis in end stage renal disease Egyptian patients on maintenance haemodialysis

In end stage renal disease, inflammation is considered a critical regulator of atherosclerotic plaque formation and progression, to which many dialysis and non-dialysis-related factors may contribute. Since circulating inflammatory cytokine levels vary inter-individually, one may speculate that genetic factors, such as polymorphisms in genes encoding them, may be involved in determining the individual inflammatory reaction in response to a given insult. The present work aimed to study interleukin-1B (-511C/T), and interleukin-6 (-174G/C) gene polymorphisms and their possible association with atherosclerosis in Egyptian patients with end stage renal disease on maintenance haemodialysis. The present study was conducted on 100 Egyptian subjects, the control group (n= 30) and the patient group (n= 70) with end stage renal disease on maintenance haemodialysis which were further subdivided into two subgroups with (n= 33) and without atherosclerosis (n= 37) as evidenced by CIMT, ECG ischaemic changes, cerebrovascular insufficiency (CVI), and peripheral vascular insufficiency (PVI). All studied subjects were subjected to detailed history taking, routine laboratory investigations and molecular studies including detection of IL-1B (-511C/T) and IL-6 (-174G/C) gene polymorphisms using the Polymerase chain reaction/ Restriction fragment length polymorphism (PCR/RFLP) technique. The genotype distribution and allele frequency of IL-1B (-511C/T) and IL-6 (-174G/C) showed no statistical significant difference among the studied groups. To conclude the development of atherosclerosis among Egyptian patients on maintenance haemodialysis cannot be attributed to these two gene polymorphisms

Impact of different levels of dietary myo-inositol on the growth performance, histological structure of gonads and liver of red tilapia reared in brackish water

A 120 day growth trial was conducted to evaluate the dietary inositol using diets (25.7% crude protein pelleted diet). These diets were formulated to contain graded levels of supplemental myo-inositol (MI) (0, 300, 400 and 500 mg/kg). Four conical bottom fiberglass tanks (500 L.) were used and stocked with fifty red tilapia in each tank with initial weight (average weight) of 1.82 g ± 0.03). Fishes were fed twice daily at a rate of 8% of live body weight for 6 days a week. Significantly, the best value of average final body weight was observed at 500 mg/kg inositol (MI) followed by 400 mg/kg diets (p.0.05). Female red tilapia which fed on diets that contained 400 and 500 mg/kg inositol showed many types of atresia, each one had its specific feature such as degeneration of the nucleus, liquification of cytoplasm and yolk. Also, hypertrophy of the follicular cell acted as phagocytic cells which invaded the oocyte from out side. The testis of red tilapia fed diets supplemented with 300 and 400 mg/kg was not affected by dietary treatments and the results revealed normal development of active spermatogenesis process at maturation, nearly ripe and spawning stages, while the testis of fish fed diets supplemented with 500mg/kg showed resorption of spermatozoa and thick lobules boundary tissue. The liver of fish fed diets that contained 300 mg/kg (MI) revealed that hepatocytes had distracted membrane and faintly stained cytoplasm. Pycnotic nuclei are common. With increased dose of (MI) to 400 mg/kg the pyenotic nuclei and cytoplasmic vacuolation was obtained. With increased dose of (MI) to 500 mg/kg diets, lipid infiltration, lipid metabolic disturbance resulted in the accumulation of lipid in liver, decreased hepaticlipoprotein output and intestinal lipodystrophy. The recommended dose is 400 mg/kg diets to obtain normal males. Also, the results explained the mechanism of inositol action through reproduction dysfunctions and recruitment failure which occurred at dose more than 400 mg/kg (MI) and the recruitment caused a reduction in population size

Cure of post Kala-azar dermal leishmaniasis with paromomycin/sodium stibogluconate combination: a proof of concept

Background: Post kala-azar dermal leishmaniasis (PKDL) is  a  recognized  dermatologic  complication  of  successfully  treated  visceral  leishmaniasis  (VL). PKDL lesions are suspected to be important reservoirs for VL transmission in Sudan. Prolonged treatment schedules, feeling of general well-being and the social stigmata of PKDL prevent most patients seeking treatment. The mainstay of treatment is cardiotoxic sodium stibogluconate (SSG) for 60-120 days. Recently, liposomal amphotericin B (Ambisome®) and immunochemotherapy gave promising results. Ambisome® is expensive and difficult to prepare under field conditions. Paromomycin/SSG combination has been shown to be safe, efficacious and can save time in VL treatment. This study aims to prove that Paromomycin/SSG combination can cure and reduce PKDL treatment duration.Methods:We are reporting nine cases of patients with PKDL lesions of ≥6 months duration who were diagnosed by clinical signs, histopathological/immunohistochemical and PCR.Results: Patients’ mean age was 11.7 ± 4.3 years. A third of the patients (3/9; 33.3%) who failed previous SSG treatment of 2-3 months duration responded completely to 40 days of paromomycin/SSG combination. The majority of patients (5/9; 55.6%) responded completely to 30 days of the combination. One patient (1/9; 11.1%) relapsed following 30 days paromomycin/SSG combination.Conclusion:It was concluded that paromomycin/SSG combination for 30 days is time-saving, safe and efficacious for PKDL treatment.

Safety and immunogenicity of an autoclaved Leishmania major vaccine

Objective: To test the safety and immunogenicity of two doses of autoclaved L.major (ALM) vaccine mixed with BCG.Setting: Kala-azar endemic area of eastern Sudan.Design: This was a randomised, double blind and BCG controlled phase I/II study.Subjects: Eighty healthy volunteers (forty children and forty adults) with no past history of kala-azar, no reactivity to leishmanin antigen and with a reciprocal direct agglutination test (DAT) titre o

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy

Silencing CD36 gene expression results in the inhibition of latent-TGF-β1 activation and suppression of silica-induced lung fibrosis in the rat

<p>Abstract</p> <p>Background</p> <p>The biologically active form of transforming growth factor-β1 (TGF-β1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-β1 (L-TGF-β1) to active TGF-β1. To clarify the role of CD36 in the development of silica-induced lung fibrosis, a rat silicosis model was used to observe both the inhibition of L-TGF-β1 activation and the antifibrotic effect obtained by lentiviral vector silencing of CD36 expression.</p> <p>Methods</p> <p>The rat silicosis model was induced by intratracheal injection of 10 mg silica per rat and CD36 expression was silenced by administration of a lentiviral vector (Lv-shCD36). The inhibition of L-TGF-β1 activation was examined using a CCL-64 mink lung epithelial growth inhibition assay, while determination of hydroxyproline content along with pathological and immunohistochemical examinations were used for observation of the inhibition of silica-induced lung fibrosis.</p> <p>Results</p> <p>The lentiviral vector (Lv-shCD36) silenced expression of CD36 in alveolar macrophages (AMs) obtained from bronchoalveolar lavage fluid (BALF) and the activation of L-TGF-β1 in the BALF was inhibited by Lv-shCD36. The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups. The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups. The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups.</p> <p>Conclusion</p> <p>These results indicate that silencing expression of CD36 can result in the inhibition of L-TGF-β1 activation in a rat silicosis model, thus further preventing the development of silica-induced lung fibrosis.</p