Action mechanisms and biocontrol of Purpureocillium lilacinum against green mould caused by Penicillium digitatum in orange fruit.

AIMS: The present study evaluated, for the first time, the inhibitory effects of the filtrate of Purpureocillium lilacinum against Penicillium digitatum. METHODS AND RESULTS: No direct contact between P. lilacinum and P. digitatum was observed during the dual culture test and the inhibition zone was 6·1 mm. The filtrate of P. lilacinum completely inhibited P. digitatum growth and spore germination at the concentration of 64%. The filtrate increased the permeability of the cell membrane and the content of MDA in P. digitatum. The ergosterol content in P. digitatum was strongly inhibited at 32% by 81·1%. The green mould incidence and severity in filtrate-treated fruit at 64% were 71·7 and 80·7% lower than in the control, respectively. The filtrate enhanced the activity of PAL, PPO and POD enzymes in orange fruit. The POD and PAL gene expression levels were significantly upregulated in the fruit treated with the filtrate. CONCLUSIONS: This study indicated that the antifungal mechanism of P. lilacinum filtrate against P. digitatum is mainly by the damage of the fungal cell membrane and its components. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides the pioneer evidence on the application of P. lilacinum filtrate as a novel biocontrol agent for orange green mould.

The prevalence of factor VIII and IX inhibitors among Saudi patients with hemophilia: Results from the Saudi national hemophilia screening program.

Hemophilia A and B are X-linked diseases that predominantly affect male patients. Patients can develop coagulation factor inhibitors, which exponentially increases the treatment cost. However, the prevalence of factor VIII and IX inhibitors in Saudi Arabia is unclear.This study aimed to determine the Saudi prevalence of factor VIII and IX inhibitors.This 4-year, 7-center, cross-sectional study evaluated the Saudi prevalences of hemophilia A and B. We collected the patients' clinical data, evaluated their disease, and tested for factor inhibitors.We included 202 patients with hemophilia (median age at diagnosis: 0.13 years, range: birth-34.8 years). The patients included 198 male patients (98%), 148 patients with hemophilia A (73.3%), and 54 patients with hemophilia B (26.7%). The patients exhibited severe factor VIII activity (<1%; 121 patients; 5.2%), moderate activity (1-5%; 7 patients; 4.9%), and mild activity (14 patients; 9.9%). Among the patients with care-related data, most patients were treated for episodic bleeding (76.8%) or received prophylaxis (22.6%); 1 patient received both treatments. Among the patients with source-related data, the factor replacements were derived from plasma (48.4%), recombinant concentrates (22.9%), both sources (14.6%), or fresh frozen plasma (14.1%). Factor VIII inhibitors were observed in 43 (29.3%) of the 147 patients, and only 1 of the 54 patients developed factor IX inhibitors. Most patients who developed inhibitors had severe hemophilia (40/44; 90.9%), and inhibitors were also common among patients who received recombinant products (14/43; 32.6%).The Saudi prevalence of factor inhibitors was similar to those among other ethnic populations.

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure.

BM failure (BMF) is a major and frequent complication of dyskeratosis congenita (DKC). Allogeneic hematopoietic SCT (allo-HSCT) represents the only curative treatment for BMF associated with this condition. Transplant-related morbidity/mortality is common especially after myeloablative conditioning regimens. Herein, we report nine cases of patients with DKC who received an allo-SCT at five different member centers within the Eastern Mediterranean Blood and Marrow Transplantation Registry. Between October 1992 and February 2011, nine DKC patients (male, 7 and female, 2), with a median age at transplantation of 19.1 (4.9-31.1) years, underwent an allo-HSCT from HLA-matched, morphologically normal-related donors (100%). Preparative regimens varied according to different centers, but was reduced intensity conditioning (RIC) in eight patients. Graft source was unstimulated BM in five cases (56%) and G-CSF-mobilized PBSCs in four (44%) cases. The median stem cell dose was 6.79 (2.06-12.4) × 10(6) cells/kg body weight. GVHD prophylaxis consisted of CsA in all nine cases; MTX or mycophenolate mofetil were added in five (56%) and two (22%) cases, respectively. Anti-thymocyte globulin was administered at various doses and scheduled in four (44%) cases. Median time-to-neutrophil engraftment was 21 (17-27) days. In one case, late graft failure was noted at 10.4 months post allo-HSCT. Only one patient developed grade II acute GVHD (11%). Extensive chronic GVHD was reported in one case, whereas limited chronic GVHD occurred in another four cases. At a median follow-up of 61 (0.8-212) months, seven (78%) patients were still alive and transfusion independent. One patient died of metastatic gastric adenocarcinoma and graft failure was the cause of death in another patient. This study suggests that RIC preparative regimens are successful in inducing hematopoietic cell engraftment in patients with BMF from DKC. Owing to the limited sample size, the use of registry data and heterogeneity of preparative as well as GVHD prophylaxis regimens reported in this series, we are unable to recommend a particular regimen to be considered as the standard for patients with this disease.

HER2 over expression in malignant palpable breast lumps of pre and postmenopausal women attending RICK

Back ground: Human Epidermal growth factor Receptor 2 (HER-2/neu) over expression in breast cancer is associated with poor outcome and decrease disease free survival (DFS). The aim of this study was to evaluate the over expression of HER2/neu among premenopausal and postmenopausal females presented with malignant palpable breast lumps to Radio Isotope Center Khartoum (RICK). Methods: The study was a case-control conducted among patients attending Radiation Isotopes Centre Khartoum (RICK). A total of 328 women were randomly selected. Data were collected by a pre coded; pre tested questionnaire. Tissue biopsies of breast lumps had been analyzed using immunohistochemical techniques for HERR-2/neu over expression and its relation to other prognostic factors was evaluated. Results: HER-2/neu + vein first pregnancy at 23 years; were 32 (41) in the cases; 6 (35) in the controls of premenopausal women; and 21(44) in the cases; 5 (38) in the controls of postmenopausal women. HER-2/neu + veexpression in relation to age at menarche 12 years was 39 (51) in the cases; 7(39) in the controls of premenopausal women; and 36 (56) in the cases; 7 (45) in the controls of postmenopausal women. HER-2/neu+ vein relation to Body Mass Index 29 kg/m2 showed 7 (37) in the cases; 2 (33) in the controls of premenopausal women (x2=0.024); and 8(38) in the cases; 2(40) in the controls of postmenopausal women (x2= 0.006). HER-2/neu+ veexpression in relation to history of abortion or miscarriage (ever) was found to be 21 (39) in the cases; 4 (33) in the controls of premenopausal women; and 18 (44) in the cases; 3 (33) in the controls among postmenopausal women. HER-2/neu+ veexpression in relation to the history of breast cancer in a first degree relatives was 3 (25) in the cases; 1(50) in the controls of premenopausal women; and 4 (22) in the cases; 2 (28) in the controls of postmenopausal women. HER-2/neu+ veexpression in relation to the use of oral contraceptives was 3 (37) in the cases; 1(50) in the controls among premenopausal women; and 3 (27) in the cases; 1 (50) in the controls of postmenopausal women. Conclusion: The study confirmed an etiological association between HER2/neu+ve and HER2/neu - ve and age at first pregnancy . 23 years; age of menarche at _ 12 years; abortion or miscarriage in premenopausal and post menopausal Sudanese women; while an etiological association was confirmed between HER2/neu+ve and HER2/neu -ve; and BMI in pre menopausal women; and the family history of cancer in post menopausal women

Mutations in SECISBP2 result in abnormal thyroid hormone metabolism.

Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins. Mice lacking tRNA(Sec) die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans. Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. We identified three of seven siblings with clinical evidence of abnormal thyroid hormone metabolism. Their fibroblasts showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. Systematic linkage analysis of genes involved in DIO2 synthesis and degradation led to the identification of an inherited Sec incorporation defect, caused by a homozygous missense mutation in SECISBP2 (also called SBP2). An unrelated child with a similar phenotype was compound heterozygous with respect to mutations in SECISBP2. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.