In ovo injection of AZD6244 suppresses feather follicle development by the inhibition of ERK and Wnt/ß-catenin pathways in goose embryos (Anser cygnoides).

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value.2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and ß-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while ß-catenin protein was highly expressed in the middle stage of embryo development.3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/ß-catenin pathway protein expression.4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/ß-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, ß-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of ß-catenin and p-ERK were consistent with Western blot results.5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/ß-catenin pathways.

Comparison of Transversus Thoracis Muscle Plane Block and Pecto-Intercostal Fascial Plane Block for enhanced recovery after pediatric open-heart surgery.

BACKGROUND: Effective analgesia after cardiac surgery contributes to enhanced recovery. AIM: To compare the perioperative analgesic effectiveness of Transversus Thoracis Muscle Plane Block (TTPB) and Pecto-Intercostal-Fascial Plane Block (PIFB) for controlling post-sternotomy pain in the pediatric population for ultrafast track cardiac surgery. METHODS: Double-blind randomized study of 60 children, 2-12 years old, undergoing cardiac surgery via median sternotomy in whom a bilateral ultrasound-guided TTPB or TIBP block was performed preemptively. RESULTS: Epidemiologic data of both groups were comparable. TTPB group had a lower median Modified Objective Pain Score (MOPS) all over the time postoperatively. Fentanyl consumption was significantly lower in TTBP group compared with PIFB group, only 4/30 received supplemental fentanyl during surgery in the TTPB group vs. 11/30 in the PIFB group (p = 0.033). The median [interquartile] values of postoperative fentanyl consumption were significantly lower in the TTBP compared with PIFB group: 12.0 [10.0-12.0] vs. 15.0 [15.0-16.0] µg/kg (p < 0.001), respectively. First rescue analgesia was later in the TTPB group compared to the PIFB group with median times of 7.25 and 5.0 h, respectively (p < 0.001). Both groups had a comparable ICU length of stay (p = 0.919), with a median of 3 days. Furthermore, in the PIFB group, the incidence of non-sternal wound chest pain (53.3%) was significantly higher than in the TTPB group (3.3%) (p < 0.05). CONCLUSION: TTPB and PIFB are safe regional blocks that could enhance recovery after pediatric cardiac surgery. In our series, TTPB provided better and longer-lasting postoperative analgesia with less incidence of non-sternal wound pain than PIFB.

Clinicopathological correlations of renal pathology: A single center experience.

To evaluate the clinicopathological correlation of renal pathology and outline the frequencies of different renal diseases, beside assessment of lupus nephritis (LN), we studied 150 patients [72 (48%) males and mean age of 33.82 ± 15.4 years] who were subjected to native renal biopsy; 112 (72.8%) biopsied patients were diagnosed to have glomerulonephritis (GN). The most frequent clinical renal syndrome was nephrotic syndrome found in 55 (36.6%) patients, followed by nephritic syndrome in 38 (25.3%) patients, chronic kidney disease in 28 (18.6%) patients, acute kidney injury (AKI) in 17 (11.3 %) patients, and subnephrotic proteinuria (SNP) in 12 (8%) patients. Focal segmental glomerulosclerosis (FSGS) was the most common patterns in primary GN (16.6%), LN was the most common pathology in secondary GN (33.3%). LN represented 18.1% of nephrotic syndrome, 68.3% of nephritic syndrome, 35.2% of AKI, and 58% of SNP. FSGS was the most common pattern in obese patients (58%), membranoproliferative GN (MPGN) was the most common pattern in hepatitis-C virus +ve patients (66.6%) and mem- branous GN was the most common pattern in hepatitis-B virus +ve patients (66.6%). In conclusion, GN was the most common pathology in this study, FSGS and MPGN were the most common patterns in primary GN.

Frequency of the Original Kidney Disease and Its Effect on the Outcome of Kidney Transplant in the Urology-Nephrology Center Mansoura University.

OBJECTIVES: Renal allograft function and graft survival depends on many factors, including the source of the graft, immunologic matching between donor and recipient, incidence of acute rejection, and recurrence of the original kidney disease. This work aimed to evaluate the effects of the original kidney disease on patient and graft survival. MATERIALS AND METHODS: This was a retrospective, single-center study that included 2189 kidney transplant recipients who were transplanted at The Urology and Nephrology Centre, Mansoura University, between 1976 and 2010. Of 2189 recipients, 1350 patients with unknown original kidney disease were excluded, with the remaining 839 patients divided into 4 groups according to their original kidney disease. RESULTS: We found pretransplant dialysis and blood transfusion to be statistically significant among the 4 groups. Regarding induction immunosuppressive therapy, a statistical significance was found between the 4 groups regarding the presence and type of induction therapy, with no statistical significance regarding the type of maintenance immunosuppression. There was no statistical significance between the 4 groups regarding the incidence of acute and chronic rejection. We also found recurrence of original kidney disease to be statistically significant in the 4 groups, particularly in the group that included patients with glomerular disease, where the highest rate of recurrence was reported in patients with focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis, and patient and graft survival was also statistically significant. CONCLUSIONS: The original kidney disease has an effect on renal allograft function and graft and patient survival.

Effect of pretransplant hepatitis C virus on the development of new-onset diabetes mellitus after transplant in Egyptian living-donor renal allotransplant recipients at Mansoura Urology and Nephrology Center.

OBJECTIVES: New-onset diabetes mellitus after transplant is a common complication in renal allograft recipients. Recently, a high prevalence of diabetes mellitus has been reported in patients with chronic hepatitis C virus. The association between hepatitis C and diabetes mellitus is well demonstrated in the general population, but some controversy still exists. This work aimed to study the effect of pretransplant hepatitis C virus on the development of new-onset diabetes mellitus after transplant in Egyptian living-donor renal allotransplant recipients. MATERIALS AND METHODS: This retrospective single center study included 913 kidney transplant recipients who were transplanted at Mansoura Urology and Nephrology Center between 2000 and 2010. The patients were divided into 4 groups according to their hepatitis C virus serology and diabetic status. RESULTS: Pretransplant dialysis duration and number of blood transfusion units were statistically significant among both viremic and nonviremic groups. With respect to induction therapy, a highly statistical significance was observed between the 4 groups regarding presence and type of adjuvant therapy (P < .001). With respect to maintenance immunosuppression, high statistically significant results were observed regarding steroid and rapamycin between the 4 groups (P < .001) with lower significance regarding mycophenolate mofetil (P = .04) but no significance regarding azathioprine, cyclosporine, or tacrolimus therapy. Incidence of new-onset diabetes mellitus after transplant was statistically higher in the viremic than nonviremic group (P < .001). CONCLUSIONS: There was a positive correlation between incidence of new-onset diabetes mellitus after transplant and positive pretransplant hepatitis C virus status.

Endothelial nitric oxide synthase gene polymorphisms and the risk of diabetic nephropathy in type 2 diabetes mellitus.

Endothelial dysfunction plays an important role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy (DN). Endothelial nitric oxide synthase (eNOS) gene polymorphisms that affect eNOS activity are associated with endothelial dysfunction. The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients. A total of 400 type 2 diabetic patients were enrolled in this study. The DN group comprised 200 patients; the group of diabetics without nephropathy comprised another 200 patients. Genetic analysis for eNOS gene polymorphisms was done in all subjects. Measurement of nitric oxide levels was estimated. The C allele for -786T>C and the T allele for 894G>T were significantly more frequent in diabetics with nephropathy than in diabetics without nephropathy (p<0.001; odds ratio [OR] and 95% confidence interval [CI] for the C allele=1.64 [1.24-2.17] and p<0.001; OR and 95% CI=1.7 [1.27-2.26] for the T allele). The haplotypes CTa (with all the mutant alleles) and CTb were significantly more common in patients with DN (p=0.01 and 0.003, respectively). These results suggested that the eNOS polymorphisms might represent genetic determinants for developing DN in type 2 diabetic Egyptians.

New data on the occurrence of ochratoxin A in human sera from patients affected or not by renal diseases in Tunisia.

Ochratoxin A is often found in the sera of people exposed to this mycotoxin in their food (cereals such as barley, coffee, wines, fruit juices, spices, products of animal origin such as pig and poultry offal). Ochratoxin A is suspected of playing a role in the Balkan Endemic Nephropathy, a nephropathology described in Balkan areas where ochratoxin A is often found in cereals and in pork-derived products. In North Africa like Tunisia where high incidence of chronic interstitial nephropathies of unknown aetiology are pointed out, the involvement of ochratoxin A was suspected but contradictory studies on the degree of human exposure did not succeed in evidencing the role of ochratoxin A. In the present work, sera from 47 volunteers hospitalised for nephropathic damages including bladder tumours (21 people), and from 62 patients hospitalised for disorders other than nephropathic ones, were analysed for ochratoxin A contents. The determination of ochratoxin A in sera was done by a validated immunoaffinity-HPLC method. Sera from unaffected population exhibited percentages of 74.2%, 22.6% and 3.2% containing ranges of ochratoxin A as <0.10-0.5 microg/l, 0.51-1.0 microg/l and above 1.0 microg/l respectively. For patients affected with renal diseases, percentages were 59.5%, 25.5% and 14.9% on the same ranges of ochratoxin A levels respectively. The average ochratoxin A concentration for patients with urinary tract disease excluding cancer patients was 0.99+/-1.28 microg/l while that for the non-nephropathic patients was 0.53+/-1.00 microg/l. However the average levels in the cancer patients was only 0.26+/-0.20 microg/l. Those results are in line with most of previously published works and did not confirm very high ochratoxin A contents found in other reports from same regions.