Publications by authors named "Ahmed Gaballah"

19 Publications

  • Page 1 of 1

Biomaterial-Based Nanocomposite for Osteogenic Repurposing of Doxycycline.

Int J Nanomedicine 2021 12;16:1103-1126. Epub 2021 Feb 12.

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.

Background: Besides its antimicrobial action, doxycycline (DX) has lately been repurposed as a small-molecule drug for osteogenic purposes. However, osteogenic DX application is impeded by its dose-dependent cytotoxicity. Further, high-dose DX impairs cell differentiation and mineralization.

Purpose: Integrating DX into a biomaterial-based delivery system that can control its release would not only ameliorate its cytotoxic actions but also augment its osteogenic activity. In this work, we managed to engineer novel composite DX-hydroxyapatite-polycaprolactone nanoparticles (DX/HAp/PCL) to modify DX osteogenic potential.

Methods: Employing a 2-factorial design, we first optimized HApN for surface-area attributes to maximize DX loading. Composite DX/HAp/PCL were then realized using a simple emulsification technique, characterized using various in vitro methods, and evaluated for in vitro osteogenesis.

Results: The developed HApN exhibited a favorable crystalline structure, Ca:P elemental ratio (1.67), mesoporous nature, and large surface area. DX/HAp/PCL achieved the highest reported entrapment efficiency (94.77%±1.23%) of DX in PCL-based particles. The developed composite system achieved controlled release of the water-soluble DX over 24 days. Moreover, the novel composite nanosystem managed to significantly ameliorate DX cytotoxicity on bone-marrow stem cells, as well as enhance its overall proliferation potential. Alkaline phosphatase and mineralization assays revealed superior osteodifferentiation potential of the composite system. Quantification of gene expression demonstrated that while DX solution was able to drive bone-marrow stem cells down the osteogenic lineage into immature osteoblasts after 10-day culture, the innovative composite system allowed maturation of osteodifferentiated cells. To the best of our knowledge, this is the first work to elaborate the impact of DX on the expression of osteogenic genes: , OSP, and BSP. Further, the osteogenicity of a DX-loaded particulate-delivery system has not been previously investigated.

Conclusion: Our findings indicate that repurposing low-dose DX in complementary biomaterial-based nanosystems can offer a prominent osteogenic candidate for bone-regeneration purposes.
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http://dx.doi.org/10.2147/IJN.S298297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887185PMC
March 2021

Hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles for enhanced osteogenesis.

Mater Sci Eng C Mater Biol Appl 2021 Feb 8;119:111599. Epub 2020 Oct 8.

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address:

Hydroxyapatite nanoparticles (HApN) are largely employed as osteogenic inorganic material. Inorganic/polymeric hybrid nanostructures can provide versatile bioactivity for superior osteogenicity, particularly as nanoparticles. Herein, we present hybrid biomaterial-based hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) realized using simple preparation techniques to augment HApN osteogenicity. Using wet chemical precipitation, we optimized HApN crystalline properties utilizing a 2-factorial design. Optimized HApN exhibited typical Ca/P elemental ratio with high reaction yield. Surface area analysis revealed their mesoporous nature and high surface area. Hybrid HAp/PCL NPs prepared using direct emulsification-solvent evaporation maintained HApN crystallinity with no observed chemical interactions. To the best of our knowledge, we are the first to elaborate the biocompatibility and osteogenicity of nanoparticulate hybrid HAp/PCL. Hybrid HAp/PCL NPs outperformed HApN regarding mesenchymal cell proliferation and osteodifferentiation with reduction of possible cytotoxicity. Unlike HApN, hybrid HAp/PCL NPs presented moderate expression of early osteogenic markers, Runx-2 and osteopontin and significantly elevated expression of the late osteogenic marker, bone sialoprotein after 10-day culture. Our results indicate that hybrid bioactive HAp/PCL NPs could offer a more prominent osteogenic potential than plain HApN for bone regenerative applications as a standalone nanoplatform or as part of complex engineered systems.
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http://dx.doi.org/10.1016/j.msec.2020.111599DOI Listing
February 2021

lnc-HOTAIR predicts hepatocellular carcinoma in chronic hepatitis C genotype 4 following direct-acting antivirals therapy.

Mol Carcinog 2020 12 19;59(12):1382-1391. Epub 2020 Oct 19.

Department of Clinical Pharmacy, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt.

Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.
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http://dx.doi.org/10.1002/mc.23263DOI Listing
December 2020

Molecular strain typing of multidrug-resistant Klebsiella pneumoniae: capsular wzi gene sequencing versus multiple locus variable number tandem repeat analysis.

Diagn Microbiol Infect Dis 2020 Nov 12;98(3):115139. Epub 2020 Jul 12.

Department of Microbiology, Medical Research Institute, Alexandria University, Egypt. Electronic address:

This study compared genotyping of Klebsiella pneumoniae isolates by 2 molecular methods. Genotyping of 50 multidrug-resistant (MDR) and 10 non-MDR K. pneumoniae subsp. pneumoniae isolates from 2 hospitals was done using multiple locus variable number tandem repeat analysis (MLVA) and capsular typing by wzi gene sequencing. Genotyping of the isolates by the 2 methods showed 100% typeability. Agreement on clustering of the isolates by the 2 methods was 82.6%. Typing by MLVA, however, was more discriminatory (97%) than by wzi gene sequencing (92%). All the 23 K. pneumoniae subsp. pneumoniae isolates randomly selected for wzi gene sequencing showed sequence identity to previously published wzi sequences, which enabled prediction of the K-types of 16 of them. The 2 methods revealed the relatedness of (8/15) isolates from 1 of the 2 hospitals. MLVA may be considered a cheaper and more discriminatory molecular typing method suitable for genotyping of K. pneumoniae isolates in developing countries.
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http://dx.doi.org/10.1016/j.diagmicrobio.2020.115139DOI Listing
November 2020

Molecular Characterization of Giardia intestinalis Detected in Humans and Water Samples in Egypt.

Acta Parasitol 2020 Jun 2;65(2):482-489. Epub 2020 Mar 2.

National Blood Transfusion Services, Ministry of Health, Damanhour, Egypt.

Background: Giardia intestinalis is a common cause of gastrointestinal illness especially in children of developing countries. Giardia assemblages A and B are the major human infective genotypes.

Objective: The present study aimed to investigate the role of water supply in the epidemiology of giardiasis via genotyping G. intestinalis detected in diarrheic children and in water samples in Egyptian rural areas.

Methods: Stool samples of 100 diarrheic children, 40 drinking water samples and 10 raw water samples of canals were examined microscopically for Giardia. DNA was extracted from microscopically positive faecal samples and from all of the collected water samples. Amplification of Giardia tpi gene was performed by a nested PCR using assemblage A- and assemblage B-specific primers. Giardia gdh gene was amplified by a heminested PCR. Giardia genotypes were determined by restriction fragment polymorphism (RFLP) analysis of the amplified products. Sequencing of the amplified products was performed in two faecal and two water samples RESULTS: Giardia intestinalis was detected in 24 children, in none of the drinking water samples and in all canal water samples. Giardia sub-assemblage AII was identified in all stool and raw water samples. The RFLP pattern was confirmed in sequenced samples.

Conclusion: The presence of the same Giardia sub-assemblage in diarrheic children and in raw water samples shows by molecular evidence the potential for waterborne dissemination of Giardia in Egypt. Further studies are needed to monitor cyst levels and infectivity of the genotype detected in water for risk assessment and management.
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http://dx.doi.org/10.2478/s11686-020-00176-4DOI Listing
June 2020

Relation between microRNA-21, transforming growth factor β and response to treatment among chronic hepatitis C patients.

J Med Virol 2019 12 11;91(12):2166-2173. Epub 2019 Aug 11.

Department of Internal Medicine, National Research Center, Cairo, Egypt.

Background: Persistence of hepatitis C virus (HCV) infection and response to antiviral therapy has been shown to be associated with inappropriate levels of cytokines and microRNAs (miRNAs). miRNA levels have been reported to fluctuate during treatment. Thus they could be useful predictors for responses to treatment among HCV infected patients, thereby reducing ineffective treatments.

Aim: The current study aimed to investigate the relation between miRNA-21 expression profiles, transforming growth factor β (TGF-β) serum levels and response to treatment with the new direct antiviral drugs (sofosbuvir + daclatasvir ± ribavirin), among HCV infected Egyptian patients.

Subjects And Methods: This prospective study was conducted on 50 HCV infected patients (before and after treatment) and 20 healthy volunteers. miRNA expression profiles were determined by real-time polymerase chain reaction and TGF-β1 serum levels were measured by using enzyme-linked immunosorbent assay.

Results: There was a significant increase in serum albumin, platelets count and a significant decrease in liver enzymes, serum bilirubin, and prothrombin time after treatment. Significant reduction of viral load among HCV patients after receiving the treatment was reported. Concomitantly, there was an increase in the relative quantity of miRNA-21 (P = .001*) and serum levels of TGF-β1 ( P = .337) among HCV patients after receiving treatment.

Conclusion: Nearly all responders to direct antiviral drugs showed increased levels of both miRNA-21 and TGF-β1. This may indicate an interplay between TGF-β1 and miRNA-21 during remission or progression of viral infection. Thus miRNA-21 could be used as promising serum biomarker, for assessment of antiviral treatment efficacy and improvement of fibrosis among chronically infected HCV patients.
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http://dx.doi.org/10.1002/jmv.25559DOI Listing
December 2019

Tumor microenvironmental plasmacytoid dendritic cells contribute to breast cancer lymph node metastasis via CXCR4/SDF-1 axis.

Breast Cancer Res Treat 2019 Apr 10;174(3):679-691. Epub 2019 Jan 10.

Department of Zoology, Faculty of Science, Cairo University, 12613, Giza, Egypt.

Purpose: Plasmacytoid dendritic cells (PDCs) infiltration into breast cancer tissues is associated with poor prognosis. Also, CXCR4 shows compelling evidences to be exploited by cancer cells to migrate to distant sites. The present study investigated lymph node metastasis in the light of PDCs infiltration and the potential cross talk with CXCR4/SDF-1 chemokine axis.

Methods: We assessed circulating PDCs proportions drained from the axillary tributaries, and the in situ expression of both CD303 and CXCR4 in breast cancer patients with positive lymph nodes (pLN) and negative lymph nodes (nLN) using immunohistochemistry and flow cytometry. We also analyzed the expression of SDF-1 in lymph nodes of pLN and nLN patients. We studied the effect of the secretome of PDCs of pLN and nLN patients on the expression of CXCR4 and activation of NF-κB in human breast cancer cell lines SKBR3 and MCF-7. TNF-α mRNA expression level in PDCs from both groups was determined by qPCR.

Results: Our findings indicate increased infiltration of PDCs in breast cancer tissues of pLN patients than nLN patients, which correlates with CXCR4 cells percentage. Interestingly, SDF-1 is highly immunostained in lymph nodes of pLN patients compared to nLN patients. Our in vitro experiments demonstrate an upregulation of NF-κB expression and CXCR4 cells upon stimulation with PDCs secretome of pLN patients than those of nLN patients. Also, PDCs isolated from pLN patients exhibited a higher TNF-α mRNA expression than nLN patients. Treatment of MCF-7 cell lines with TNF-α significantly upregulates CXCR4 expression.

Conclusions: Our findings suggest a potential role for microenvironmental PDCs in breast cancer lymph node metastasis via CXCR4/SDF-1 axis.
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http://dx.doi.org/10.1007/s10549-019-05129-8DOI Listing
April 2019

Emergence of bla and bla among VIM-producing Pseudomonas aeruginosa clinical isolates in Alexandria, Egypt.

Acta Microbiol Immunol Hung 2019 Mar 7;66(1):131-142. Epub 2018 Nov 7.

1 Department of Microbiology, Medical Research Institute, Alexandria University , Alexandria, Egypt.

Thirty-three Pseudomonas aeruginosa isolates, resistant to one or more β-lactams, were included in this study. Identification of tested strains was confirmed using MALDI-TOF/MS. Phenotypic and genotypic β-lactamase patterns were investigated. Most of the isolates were resistant to carbapenems (32 out of 33) and to the extended-spectrum cephalosporins (ESC) (30 out of 33). Phenotypically, the production of extended-spectrum beta-lactamase (ESBL), metallo-β-lactamases (MBL), and carbapenemases was detected in 10, 23, and 9 isolates, respectively. However, AmpC hyperproduction was not phenotypically detected among all isolates. Genotypically, ESBL and MBL encoding genes were detected in 23 and 27 isolates, respectively. Altogether 27 strains were detected as bla positive and 16 strains carried bla gene. To the best of our knowledge, this is the first report of P. aeruginosa clinical isolates harboring bla together with bla in Egypt, where 5 of our 30 ESC-resistant isolates showed this genotype. Our results confirmed that resistance of P. aeruginosa isolates to β-lactam antibiotics is mediated via multiple β-lactamases belonging to different molecular classes. To the best of our knowledge, this is the first report of bla among P. aeruginosa clinical isolates from Egypt. Ten isolates harbored bla and five of them co-harbored bla together with bla, bla, and bla
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http://dx.doi.org/10.1556/030.65.2018.044DOI Listing
March 2019

MicroRNA-21 as a predictor and prognostic factor for trastuzumab therapy in human epidermal growth factor receptor 2-positive metastatic breast cancer.

J Cell Biochem 2019 03 23;120(3):3459-3466. Epub 2018 Sep 23.

Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Breast cancer is the second most common cancer diagnosed worldwide. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents about 20% to 30% of all breast cancers. Trastuzumab is used in the treatment of HER2-positive breast cancer. MicroRNA-21 (miR-21) is an oncomiR that acts by inhibiting many tumor-suppressor genes. We analyzed the relative expression levels of serum miR-21 in 20 HER2-positive metastatic breast cancer patients before and after 3 months of treatment with trastuzumab. miR-21 levels decreased with a high significant difference after trastuzumab therapy (P = 0.001). Although miR-21 expression levels were lower in responders than in nonresponders, the difference was not statistically significant ( P = 0.6). Our results demonstrated a significant negative correlation between its basal expression, expression levels after treatment, and time to progression ( P = 0.03 and 0.01, respectively). These results make miR-21 a potential prognostic factor for HER2-positive metastatic breast cancer patients. Additionally, it can be an interesting potential target in therapy using antisense oligonucleotides for miR-21.
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http://dx.doi.org/10.1002/jcb.27620DOI Listing
March 2019

Chemotherapy-Induced Peripheral Neuropathy in Egyptian Patients: Single Institution Retrospective Analysis

Asian Pac J Cancer Prev 2018 Aug 24;19(8):2223-2227. Epub 2018 Aug 24.

Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Email:

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity that requires treatment modification or cessation and worsens patients’ quality of life. Its incidence is 30–40%. Occurrence and severity depend on treatment- and patient-related factors. The symptoms are self-limiting with recovery rate about 50%. Methods: This retrospective analysis took place in our chemotherapy unit. We included patients treated between January 2014 and December 2015. Results: 250 patients were eligible. 53 received paclitaxel, 78 received docetaxel, 64 received cisplatin and 55 received oxaliplatin. Mean age was 50.11 years. Frequency of CIPN was 46.8% (Grade I 70.9%, GII 24.7%, GIII 4.4%). It was 74% with oxaliplatin, 73.5% with paclitaxel, 35.9% with cisplatin and 17.9% with docetaxel. After median of 6 months 24% of patients recovered completely. No significant correlation between occurrence of CIPN and age (p = 0.781), while was significant with cisplatin (p = 0.043). Diabetic patients had higher incidence (p = 0.007). With cisplatin, median cumulative dose of 450 mg/m2 and ≥ 6 cycles had higher incidence of CIPN (p 0.006 and 0.010; respectively). With oxaliplatin, none was correlated with CIPN frequence. With paclitaxel, CIPN was more frequent if ≥ 4 cycles were received (p = 0.005). With docetaxel, > 4 cycles or cumulative dose ≥ 360 mg/m2 had higher occurrence of GII CIPN (p < 0.001 for both). Conclusion: CIPN is common problem that affects patients’ quality of life and leads to treatment interruption. There are many factors affecting its incidence and severity.
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http://dx.doi.org/10.22034/APJCP.2018.19.8.2223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171376PMC
August 2018

Pre-treatment Peripheral Neutrophil-Lymphocyte Ratio as a Prognostic Marker in Gastric Cancer.

J Gastrointest Cancer 2019 Dec;50(4):763-768

Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt.

Background: Gastric cancer is the fifth cancer worldwide. Inflammatory response increases metastasis through apoptosis inhibition and angiogenesis augmentation. The neutrophil-lymphocyte ratio (NLR), which is a balance between pro-cancer inflammatory and anti-cancer immune responses, was proved as prognostic marker. Peripheral NLR is a good reflection of tumor microenvironment.

Methods: We retrospectively collected data of gastric and gastro-esophageal cancer patients treated from January 2015 till December 2016. Sixty-one patients were included. Pre-treatment NLR was calculated. We extracted the different clinic-epidemiological and pathological data. Event-free and overall survivals were plotted using Kaplan-Meier curves.

Results: The median age was 55. Male to female ratio was 1:1. Forty-seven patients were smokers. Most of the patients (93.4%) had good performance status (ECOG 0-2). Forty-six patients had gastric and 15 had gastro-esophageal cancer. 50.8% had diffuse gastric type. Grade III represented 49.2% and grade II 46%. Twelve patients had ascites at diagnosis. Stage at presentation was 1.6%, 4.9%, 27.9%, 50.8%, and 14.8% for stage I, II, III, IV, and unknown respectively. The median NLR was 2.4. The NLR showed no significant correlation with different clinic-epidemiologic and pathological variables except presence of ascites; p = 0.046. Median event-free survival (EFS) and overall survival (OS) were 6 and 8 months respectively. High NLR was significantly associated with worse survival; EFS, 5 months vs 8 months (95% CI, p = 0.001). OS, 6 months vs 9 months (95% CI, p = 0.013).

Conclusion: Gastric cancer is an aggressive and fatal disease. NLR can be used as a prognostic marker.
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http://dx.doi.org/10.1007/s12029-018-0144-xDOI Listing
December 2019

Comparison between Sigma metrics in four accredited Egyptian medical laboratories in some biochemical tests: an initiative towards sigma calculation harmonization.

Biochem Med (Zagreb) 2018 Jun;28(2):020711

Private laboratory, Helwan University, Alexandria, Egypt.

Introduction: Analytical quality is an essential requirement for best practice in any medical laboratory. Lack of a harmonized approach for sigma calculation is considered an obstacle in the objective comparability of analytical performance among laboratories adopting sigma metrics. It is urgently needed that all laboratory professionals interested in the analytical quality to work hard towards harmonization protocol for sigma calculation in order to properly select their analytical goals. This study aims at harmonization of Sigma metrics calculation in four accredited Egyptian laboratories.

Materials And Methods: This observational cross sectional study compared the sigma levels for certain biochemical parameters in the four participating laboratories.

Results: Coefficient of variation (CV) and bias were determined for some biochemical analytes, data assayed by different automated analysers in the four different accredited laboratories. The sigma level for the four medical laboratories was calculated for each biomedical parameter with changed sigma level after total allowable error (Tea) unification among participating laboratories.

Conclusion: Each laboratory should select the TEa goal based on clear standardized criteria of selection without any subjective preferences as either under or over estimation of Sigma metrics will affect the patient centred care negatively if laboratories use quality control procedures wrongly based on incorrect Sigma metrics calculation with subsequent misleading medical decisions.
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http://dx.doi.org/10.11613/BM.2018.020711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039160PMC
June 2018

Comparison of 2 different antibody assay methods, Elecsys Anti-HCVII (Roche) and Vidas Anti-HCV (Biomerieux), for the detection of antibody to hepatitis C virus in Egypt.

Diagn Microbiol Infect Dis 2018 Oct 21;92(2):107-111. Epub 2018 May 21.

Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Egypt. Electronic address:

The measurement of antibodies against hepatitis C virus (HCV) is important to screen HCV infection. The aim of this study is to investigate the reliability of 2 commercially available anti-HCV antibody kits used in routine laboratory testing in Egypt. One thousand nine hundred and thirty-one serum samples were analyzed using 2 anti-HCV test systems: Cobas e 411® Elecsys Anti-HCVII and Vidas® Anti-HCV Biomerieux. Discrepant samples were tested using the recombinant immunoblot assay Innogenetics® INNO-LIA HCV Score. Overall agreement of the 2 tests was 94%. Following discrepant sample testing by LIA, sensitivity and specificity using Vidas were 94% and 99%, respectively, while those for Cobas were 97% and 96%, respectively. This study demonstrates superior specificity by Vidas and higher sensitivity by Cobas. Both methods are suitable for laboratory and/or blood screening programs. The concomitant use of a supplementary or confirmatory assay is necessary to compare the accuracy of HCV serological assays.
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http://dx.doi.org/10.1016/j.diagmicrobio.2018.05.013DOI Listing
October 2018

Early onset breast cancer: differences in risk factors, tumor phenotype, and genotype between North African and South European women.

Breast Cancer Res Treat 2017 Nov 5;166(2):631-639. Epub 2017 Aug 5.

Department of Cancer Genetics, University of Montpellier and University Hospital (CHU), Montpellier, France.

Purpose: This report compares the risk factors, the tumor phenotypes, and the BRCA1/BRCA2 genotype of early onset breast cancer (EOBC) patients between Southern Europe and North Africa.

Methods: Four hundred and fifty six women with invasive EOBC (≤40 years) were prospectively included from four centers in France (n = 270) and four centers in North Africa (Algeria, Egypt, Morocco, Tunisia; n = 186). Life style, tumor phenotype, familial history, BRCA1/BRCA2 genotype were compared between the two populations.

Results: We found an older age at menarche, a higher number of childbearing, a more frequent breastfeeding, a higher body mass index, a lower use of oral contraceptives in North African women compared to French women. TNM stage at diagnosis was higher in North African women than in French women. North African women had a lower incidence of triple negative and proliferative (Ki 67 index > 20%) tumors. There was a lower rate of BRCA1 mutation in North Africa (7 vs. 15%, P = 0.02). Three putative BRCA1/2 founder mutations were identified in North Africa.

Conclusions: In EOBC, we found significant differences in risk factors, phenotype and a higher incidence of BRCA1 mutations in Southern Europe as compared to North Africa. The worst prognosis previously reported for EOBC in North Africa is more likely due to a higher stage at diagnosis than to a more aggressive phenotype, since triple negative tumors are more common in Southern Europe and advanced tumors in North Africa.
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http://dx.doi.org/10.1007/s10549-017-4434-yDOI Listing
November 2017

Six-week physical rehabilitation protocol for anterior shoulder dislocation in athletes.

J Exerc Rehabil 2017 Jun 30;13(3):353-358. Epub 2017 Jun 30.

Department of Kinesiology and Health Science, Utah State University, Logan, UT, USA.

Anterior shoulder dislocations are common in young athletes. The mechanism for the first or primary shoulder dislocation may involve a collision or a fall typically with the arm in an abducted and externally rotated position. The aim of this study was to design a physical rehabilitation program using the elastic band and resistive exercise to improve joint strength and range of motion in individuals diagnosed with a first-time shoulder dislocation. Twelve physically active males with a first-time acute shoulder dislocation were asked to volunteer. Participants began a physical rehabilitation program 2 weeks after the shoulder dislocation, which was confirmed by a referring physician. The rehabilitation program was 6 weeks in duration and required the participants to engage in progressive resistive loads/duration using elastic bands and weights 5 days per week. Pretest and posttest measures included shoulder strength and range of motion. All outcome measures were compared between the injured and uninjured shoulder, which served as the control condition in this study. There were statistically significant differences between the injured and uninjured shoulder for measures of strength and range of motion during pretests (<0.01) but not post-tests (<0.53). Finally, there were no differences between shoulders in regards to the volume measure suggesting that any changes in muscle atrophy or swelling were not detected. The physical rehabilitation program proposed in this study was effective at improving strength and range of motion in the injured shoulder as evidenced by the similarity in posttest values between the injured and uninjured shoulder.
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http://dx.doi.org/10.12965/jer.1734976.488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498094PMC
June 2017

Co-solvents as stabilizing agents during heterologous overexpression in Escherichia coli - application to chlamydial penicillin-binding protein 6.

PLoS One 2015 7;10(4):e0122110. Epub 2015 Apr 7.

Institute for Pharmaceutical Microbiology, University of Bonn, Bonn, Germany.

Heterologous overexpression of foreign proteins in Escherichia coli often leads to insoluble aggregates of misfolded inactive proteins, so-called inclusion bodies. To solve this problem use of chaperones or in vitro refolding procedures are the means of choice. These methods are time consuming and cost intensive, due to additional purification steps to get rid of the chaperons or the process of refolding itself. We describe an easy to use lab-scale method to avoid formation of inclusion bodies. The method systematically combines use of co-solvents, usually applied for in vitro stabilization of biologicals in biopharmaceutical formulation, and periplasmic expression and can be completed in one week using standard equipment in any life science laboratory. Demonstrating the unique power of our method, we overproduced and purified for the first time an active chlamydial penicillin-binding protein, demonstrated its function as penicillin sensitive DD-carboxypeptidase and took a major leap towards understanding the "chlamydial anomaly."
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122110PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388811PMC
December 2015

Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae.

Front Cell Infect Microbiol 2014 26;4:19. Epub 2014 Feb 26.

Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn Bonn, Germany.

For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly. D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L-alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin.
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http://dx.doi.org/10.3389/fcimb.2014.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935232PMC
September 2014

Functional analysis of the cytoskeleton protein MreB from Chlamydophila pneumoniae.

PLoS One 2011 5;6(10):e25129. Epub 2011 Oct 5.

University of Bonn, Institute for Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Section, Bonn, Germany.

In rod-shaped bacteria, the bacterial actin ortholog MreB is considered to organize the incorporation of cell wall precursors into the side-wall, whereas the tubulin homologue FtsZ is known to tether incorporation of cell wall building blocks at the developing septum. For intracellular bacteria, there is no need to compensate osmotic pressure by means of a cell wall, and peptidoglycan has not been reliably detected in Chlamydiaceae. Surprisingly, a nearly complete pathway for the biosynthesis of the cell wall building block lipid II has been found in the genomes of Chlamydiaceae. In a previous study, we discussed the hypothesis that conservation of lipid II biosynthesis in cell wall-lacking bacteria may reflect the intimate molecular linkage of cell wall biosynthesis and cell division and thus an essential role of the precursor in cell division. Here, we investigate why spherical-shaped chlamydiae harbor MreB which is almost exclusively found in elongated bacteria (i.e. rods, vibrios, spirilla) whereas they lack the otherwise essential division protein FtsZ. We demonstrate that chlamydial MreB polymerizes in vitro and that polymerization is not inhibited by the blocking agent A22. As observed for MreB from Bacillus subtilis, chlamydial MreB does not require ATP for polymerization but is capable of ATP hydrolysis in phosphate release assays. Co-pelleting and bacterial two-hybrid experiments indicate that MreB from Chlamydophila (Chlamydia) pneumoniae interacts with MurF, MraY and MurG, three key components in lipid II biosynthesis. In addition, MreB polymerization is improved in the presence of MurF. Our findings suggest that MreB is involved in tethering biosynthesis of lipid II and as such may be necessary for maintaining a functional divisome machinery in Chlamydiaceae.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025129PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187750PMC
February 2012

N-acetyl cysteine: could it be an effective adjuvant therapy in ICSI cycles? A preliminary study.

Reprod Biomed Online 2010 Jun 6;20(6):789-96. Epub 2010 Mar 6.

Al-Banoon Fertility Center, Zagazig, Egypt; Departments of Obstetrics and Gynecology, Zagazig University School of Medicine, Zagazig, Egypt.

This randomized controlled trial tested the hypothesis that addition of N-acetyl cysteine (NAC) can increase the probability of pregnancy in intracytoplasmic sperm injection (ICSI) cycles using the long agonist protocol. Women undergoing ICSI cycles due to male factor were randomly assigned to receive either long protocol (group A, 38 women) or long protocol plus NAC (group B, 38 women). Clinical pregnancy was the primary outcome. Granulosa cell apoptosis, fertilization rate, number of grade-one embryos and ongoing pregnancy were the secondary outcomes. Clinical pregnancy rate was insignificantly higher in NAC group (52.6%) than control (47.4%). Early and late apoptosis were also insignificantly lower in group B than in group A. Irrespective of the used protocol, there was significant negative correlation between both early and late apoptosis and fertilization rate (both P<0.001) and the number of good-quality embryos (P=0.007 and P<0.001, respectively). Pregnant patients had significantly lower early and late apoptosis than those who didn't achieve pregnancy (P<0.001). In conclusion, NAC supplementation did not significantly increase the probability of pregnancy in ICSI cycles using long agonist protocol. It appears that granulosa cell apoptosis may be an important prognosticator for ICSI cycle outcome.
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http://dx.doi.org/10.1016/j.rbmo.2010.03.001DOI Listing
June 2010