Publications by authors named "Mohamed Khaled"

78 Publications

Epidemiological and therapeutic aspects of acetabular fractures in elderly.

Tunis Med 2021 Feb;99(2):259-263

Introduction: Management of acetabular fracture in the elderly patients is becoming an increasingly topic of debate. Data from different parts of the world specified particularities of their patients.

Aim: To describe patterns of these fractures in the Tunisian patients aged > 60, which can contribute to management and preventive plans.

Methods: We performed a retrospective review from 1997 to 2016 treated at the Charles Nicolle university hospital. Information regarding demographics, co morbidities, mechanism of injury, Injury Severity Score (ISS), types and levels of injury, treatment type, and mortality were collected.

Results: The mean age of our patients was 68,6 years (range 60-94 years). The male to female ratio was 3:85.Main causes were motor vehicle accident. Most of our patients were in good health. The associated lesions were very frequent and present in 64.7% of cases with a clear predominance of cranio-fascial trauma, with a median of the ISS score at 11. According to the Judet and Letournel classification, 18 elementary fractures and 16 complex fractures were reported with predominance of the anterior column-posterior hemitransverse fracture pattern. Posterior wall fracture in the elderly is often associated with comminution and / or marginal impaction and / or posterior dislocation of the hip. Fractures of the anterior segment are often associated with hip protrusion and / or quadrilateral plate involvement and / or the superomedial roof impaction or "Gull sign".

Conclusion: As our population continues to age, traumatic acetabular fractures will become more prevalent. Appropriate screening strategies, treatment and prevention plans will need to be developed to improve outcomes in this devastating injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

Mechanics of guided growth of the distal femur for correction of fixed knee flexion deformities: an extra-articular technique.

Arch Orthop Trauma Surg 2021 Apr 21. Epub 2021 Apr 21.

Department of Orthopaedic and Trauma Surgery, Assiut University Hospitals, Assiut, Egypt.

Introduction: Anterior distal femoral hemiepiphysiodesis using intra-articular plates for correction of pediatric fixed knee flexion deformities (FKFD) has two documented complications: postoperative knee pain and implant loosening. The aim of this study is to investigate the mechanical properties of a novel extra-articular technique for anterior distal femoral hemiepiphysiodesis in patients with FKFD and to compare them to the conventional technique.

Materials And Methods: Sixteen femoral sawbones were osteotomized at the level of the distal femoral physis and fixed by rail frames to allow linear distraction simulating longitudinal growth. Each sawbone was tested twice: first using the conventional technique with eight plates placed anteriorly just medial and lateral to the femoral sulcus (group A) and then with plates inserted in the proposed novel location at the most anterior part of the medial and lateral surfaces of the femoral condyles with screws in the coronal plane (group B). Gradual linear distraction was performed, and the resulting angular correction was measured. Strain gauges were attached to the plates, and the amount of strain (and equivalent stress) over the plates in response to linear distraction was recorded. The two groups were compared using the Wilcoxon signed-rank test.

Results: The amount of angular correction was statistically higher in group B (extra-articular plates) at 5, 10-, and 15-mm of distraction (p < 0.001). As regards stress over the plates, the maximum stress and the area under the curve (sum of all stresses measured throughout the distraction process) were significantly higher when the plates were inserted at the conventional position (group A) (p < 0.001).

Conclusions: During anterior distal femoral hemiepiphysiodesis, the fixation of the eight plates in the coronal plane at the anterior part of the femoral condyles may produce a greater amount of correction and a lower degree of stress over the implants as compared to the conventional technique.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00402-021-03911-2DOI Listing
April 2021

The Path of Most Resistance: A Rare Instance of Metastatic Pancreatic Adenocarcinoma Identified Within Skeletal Muscle.

Cureus 2021 Mar 17;13(3):e13947. Epub 2021 Mar 17.

Radiology, University of Florida College of Medicine, Jacksonville, USA.

Soft tissue neoplastic metastases, specifically to the skeletal muscle, are uncommon in comparison to metastases within the abdomen, thorax, or intracranial regions. Specifically, pancreatic adenocarcinoma with skeletal muscle metastasis is a rare clinical phenomenon and is hardly reported. There is a high mortality rate after the diagnosis of metastatic pancreatic adenocarcinoma, attributed to inadequate screening and advanced staging upon incidental discovery. Rarely, metastatic lesions manifest in the skeletal muscle and are hardly documented. Some of the factors that deter skeletal muscle tumor implantation include the deficiency of skeletal muscle mediators and genetic makeup of the primary tumor. Surgical resection of pancreatic adenocarcinoma with adjuvant chemotherapy demonstrates the best prognosis; however, surgical management is usually limited to patients without known metastatic disease. Alternative treatment options such as chemotherapy and radiotherapy are used in the palliative care setting. Here, we present the case of a patient with previously diagnosed and treated pancreatic adenocarcinoma in remission, with biopsy-proven metastases isolated within the skeletal muscle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.13947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051535PMC
March 2021

Design, synthesis and assessment of new series of quinazolinone derivatives as EGFR inhibitors along with their cytotoxic evaluation against MCF7 and A549 cancer cell lines.

Bioorg Med Chem Lett 2021 Jun 23;41:127987. Epub 2021 Mar 23.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt. Electronic address:

New acetamide (IV a-e) and 1,3-thiazolidinone derivatives (VII a-e) were designed, synthesized and assessed for their cytotoxic activity against MCF-7 and A549 cell lines along with their lead compounds (erlotinib and gefitinib). The newly designed compounds were prepared according to the adopted procedures in schemes 1 and 2 from their quinazolinone parents. 3D QSAR pharmacophore and docking molecular modeling protocols were conducted using Discovery Studio program, beside a full biological assay for these compounds. The cytotoxicity evaluation demonstrated that compounds IVb, IVc, VIIa, VIIb, VIId exhibited potent cytotoxic activities against both MCF-7 and A549 cell lines. Moreover, the molecular modeling studies corroborated to the affinity of the compounds towards EGFR. Consequently, these five compounds were then screened for their EGFR inhibition and evaluated as well for their toxicity to normal cells, which revealed that the acetamide derivative IVc and the thiazolidinone derivative VIIa were the most potent and least toxic. DNA flow cytometry analysis was conducted for compounds IVc and VIIa, which indicated that they both induced arrest at G2/M phase of the cell cycle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2021.127987DOI Listing
June 2021

Importance of left atrial mechanical function as a predictor of atrial fibrillation risk following cardiac surgery.

Int J Cardiovasc Imaging 2021 Feb 16. Epub 2021 Feb 16.

Cairo University, Giza, Egypt.

Postoperative atrial fibrillation (POAF) after cardiac surgery is a major health problem that is associated with a significant financial burden and increased early morbidity and mortality. We investigated the accuracy of new echocardiographic derived indices to predict patients at higher risk of developing POAF. 84 consecutive patients (age 57.9 ± 6.9, 32% female) hospitalized for isolated CABG underwent comprehensive echocardiographic evaluation before surgery. Left atrial (LA) function was quantified through the assessment of phasic LA volumes to calculate LATEF. Speckle tracking echocardiography STE was used to measure LA reservoir strain, conduit strain and booster strain. Patients who developed POAF had increased LA volumes and impaired LA functions assessed by both the volumetric phasic changes and STE. By univariable analysis, all LA function parameters significantly predicted POAF. Multivariate regression analysis showed that age (P = 0.03, OR 1.134, 95% CI 1.012-1.271) and LATEF (P = 0.001, OR 0.814, 95% CI 0.725-0.914) were strong independent factors for POAF with LATEF showing the highest predictive accuracy. After multivariable adjustment to include LA strain indices to the base model, LA contractile strain LACtS (23.93 ± 4.19 vs 37.0 ± 3.35, p < 0.001) was the best discriminated for the highest predictive accuracy (OR 0.429, 95% CI 0.26-0.708). The ROC Curve was calculated for the greatest performance for prediction of POAF (AUC LACtS: 0.992; LATEF: 0.899). Adding new left atrial mechanics parameters is a more sensitive, independent tool that provides an incremental predictive value to discriminate patients at more risk for POAF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10554-021-02163-wDOI Listing
February 2021

Development and validation of GC-MS method for determination of methcathinone and its main metabolite in mice plasma and brain tissue after SPE: Pharmacokinetic and distribution study.

J Pharm Biomed Anal 2021 Feb 25;194:113798. Epub 2020 Nov 25.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia; Department of Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address:

Only focusing on the plasma levels is inadequate for the full consideration of the physiological disposition of illicit drugs in vivo. Therefore, we conducted the inclusive study on the in vivo dynamic process of intraperitoneal administration of methcathinone (MET), a well-known member of the synthetic cathinone derivatives, which is structurally similar to amphetamine analogs. This study described a validated, selective and sensitive GC-MS method for the simultaneous quantification of MET and its main metabolite, ephedrine (EPD), in the plasma and brain tissue of mice, after solid phase extraction (SPE). Ephedrine-d3 was used as an internal standard (IS). The developed method was validated following US-FDA guidelines within a concentration range of 5-1000 ng/mL for both drugs (r2 > 0.998) in the mice plasma and brain. The recoveries of MET and EPD from the mice plasma and brain ranged from 108.5 to 112.1%. The intra- and inter-day RSDs were ≤ 11.0 %. The proposed method was applied, for the first time, to investigate the pharmacokinetic (PK) and distribution study of MET and EPD following intraperitoneal administration of MET (1.4 mg/kg) to Swiss albino mice. The results exhibited that the C and T of MET in mice plasma was 517.1 ng/mL and 15 min as compared to 3.6 ng/mL and 2 h of EPD. Moreover, MET rapidly passed the blood brain barrier with C of 1444.5 ng/mL achieved at 15 min, whereas, EPD monitored C of 43.6 ng/mL at 4 h in mice brain. The highest concentration of MET in the mice brain followed by plasma was reported, with a necessity to perform more detailed clinical investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2020.113798DOI Listing
February 2021

Potential of metabolites against SARS-CoV-2 main protease supported by docking studies.

Nat Prod Res 2020 Oct 30:1-5. Epub 2020 Oct 30.

Pharmacognosy Department, Faculty of Pharmacy, Deraya University, New Minia City, Egypt.

COVID 19; an infectious disease; firstly identified in December 2019 in Wuhan, China and has since spread globally, resulting in an ongoing pandemic. Searching for protease inhibitors is a challenging task in controlling COVID 19. Genus Ficus is known to be a rich source of phenolic compounds. Metabolic profiling of leaves methanolic extract of (Moraceae) revealed nine compounds (-) mainly phenolics. Docking studies concerning these compounds against SARS-CoV-2 main protease showed that quercetin 3,7-O-α-L-dirhamnoside ( and rutin ( possessed significant binding stability at the N3 binding site in different activity degrees, which is comparable with COVID-19 main protease inhibitor, darunavir. Our study suggests that compounds quercetin 3,7-O-α-L-dirhamnoside and rutin might be potential candidates for the development of therapies against SARSCoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2020.1839452DOI Listing
October 2020

The Effect of Epilepsy and Antiepileptic Drugs on Cortical Motor Excitability in Patients With Temporal Lobe Epilepsy.

Clin Neuropharmacol 2020 Nov/Dec;43(6):175-184

Department of Neurology and Psychiatry, Assiut University Hospital, Assiut, Egypt.

Objectives: Transcranial magnetic stimulation (TMS) has been used to assess cortical disinhibition/excitation with epilepsy and determine the degree of patients' response to antiepileptic drugs (AEDs). However, the results of studies are variable and conflicting. We assessed cortical motor excitability in adults with temporal lobe epilepsy (TLE).

Methods: The TMS parameters used for assessment were: resting (RMT) and active (AMT) motor thresholds, cortical silent period (CSP), and central motor conduction time (CMCT).

Results And Conclusions: This study included 40 adults (males, 22; females, 18) with TLE with impaired awareness or to bilateral tonic clonic seizures (mean age, 32.50 ± 3.38 years; duration of illness, 6.15 ± 2.02 years) and on treatment with AEDs (valproate, 15; carbamazepine, 15; levetiracetam, 10]. The majority (62.5%) were seizure-free for ≥1 year on AEDs before TMS testing. All had normal brain magnetic resonance imaging except two, who had mesial temporal sclerosis. Comparing the entire patients with controls, patients had significantly bihemispheric higher RMT and AMT particularly over the epileptic hemisphere and shorter CSP and CMCT in the epileptic hemisphere. Shorter CSP and CMCT were observed in patients on valproate or carbamazepine and those who were uncontrolled on medications but not with levetiracetam. Significant correlations were identified between RMT and AMT (P = 0.01) and between CSP and CMCT (P = 0.001). We conclude that chronic TLE had increased cortical disinhibition in the epileptic hemisphere which can spread outside the epileptogenic zone despite the apparent control on AEDs. The TMS studies using CSP and CMCT may help future prediction of pharmacoresistance and, therefore, the need of combined AEDs with multiple mechanisms of action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNF.0000000000000412DOI Listing
September 2020

Evaluation of N-phenyl-2-aminothiazoles for treatment of multi-drug resistant and intracellular Staphylococcus aureus infections.

Eur J Med Chem 2020 Sep 25;202:112497. Epub 2020 Jun 25.

Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al- Azhar University, Cairo, 11884, Egypt; University of Science and Technology, Nanoscience Program, Zewail City of Science and Technology, October Gardens, 6th October, Giza, 12578, Egypt. Electronic address:

The increasing emergence of antibiotic-resistant bacterial pathogens calls for additional urgency in the development of new antibacterial candidates. N-Phenyl-2-aminothiazoles are promising candidates that possess potent anti-MRSA activity and could potentially replenish the MRSA antibiotic pipeline. The initial screen of a series of compounds in this novel class against several bacterial strains revealed that the aminoguanidine analogues possessed promising activities and superior safety profiles. The determined MICs of these compounds were comparable to, if not better than, those of the control drugs (linezolid and vancomycin). Remarkably, compounds 3a, 3b, and 3e possessed potent activities against multidrug resistant staphylococcal isolates and several clinically important pathogens, such as vancomycin-resistant enterococci (VRE) and Streptococcus pneumoniae. In addition, the compounds were superior to vancomycin in the rapid killing of MRSA and the longer post-antibiotic effects. Furthermore, low concentrations of compounds 3a, 3b, and 3e reduced the intracellular burden of MRSA by greater than 90%. Initial in vitro PK/toxicity assessments revealed that compound 3e was highly tolerable and possessed a low metabolic clearance rate and a highly acceptable half-life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2020.112497DOI Listing
September 2020

Design, synthesis, and biological evaluation of new pyrazoloquinazoline derivatives as dual COX-2/5-LOX inhibitors.

Arch Pharm (Weinheim) 2020 Nov 21;353(11):e2000027. Epub 2020 Jul 21.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

A new series of pyrazoloquinazoline derivatives equipped with different chalcones was designed, synthesized, and identified through H nuclear magnetic resonance (NMR), C NMR, and infrared spectroscopic techniques. Our design strategy of the quinazolinone-privileged scaffold as a new scaffold was based on merging pharmacophores previously reported to exhibit cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LOX) inhibitory activity. All the newly synthesized derivatives were biologically evaluated for COX and 5-LOX inhibitory activity and COX-2 selectivity, using celecoxib and zileuton as reference drugs, as they exhibited promising anti-inflammatory activity. Compound 3j was found to be the most promising derivative, with IC values of 667 and 47 nM against COX-1 and COX-2, respectively, which are superior to that of celecoxib (IC value against COX-2 = 95 nM), showing an SI of 14.2 that was much better than celecoxib. Compounds 3f and 3h exhibited COX-1 inhibition, with IC values of 1,485 and 684 nM, respectively. The synthesized compounds showed a significant inhibitory activity against 5-LOX, with IC values ranging from 0.6 to 4.3 µM, where compounds 3f and 3h were found to be the most potent derivatives, with IC values of 0.6 and 1.0 µM, respectively, in comparison with that of zileuton (IC  = 0.8 µM). These promising derivatives, 3f, 3h, and 3j, were further investigated in vivo for anti-inflammatory, gastric ulcerogenic effects, and prostaglandin production (PGE2) in rat serum. The molecular docking studies concerning the binding sites of COX-2 and 5-LOX revealed similar orientation, compared with reported inhibitors, which encouraged us to design new leads targeting COX-2 and 5-LOX as dual inhibitors, as a new avenue in anti-inflammatory therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.202000027DOI Listing
November 2020

Transcriptome sequencing identifies a noncoding, deep intronic variant in CLCN7 causing autosomal recessive osteopetrosis.

Mol Genet Genomic Med 2020 10 21;8(10):e1405. Epub 2020 Jul 21.

Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY, USA.

Background: Over half of children with rare genetic diseases remain undiagnosed despite maximal clinical evaluation and DNA-based genetic testing. As part of an Undiagnosed Diseases Program applying transcriptome (RNA) sequencing to identify the causes of these unsolved cases, we studied a child with severe infantile osteopetrosis leading to cranial nerve palsies, bone deformities, and bone marrow failure, for whom whole-genome sequencing was nondiagnostic.

Methods: We performed transcriptome (RNA) sequencing of whole blood followed by analysis of aberrant transcript isoforms and osteoclast functional studies.

Results: We identified a pathogenic deep intronic variant in CLCN7 creating an unexpected, frameshifting pseudoexon causing complete loss of function. Functional studies, including osteoclastogenesis and bone resorption assays, confirmed normal osteoclast differentiation but loss of osteoclast function.

Conclusion: This is the first report of a pathogenic deep intronic variant in CLCN7, and our approach provides a model for systematic identification of noncoding variants causing osteopetrosis-a disease for which molecular-genetic diagnosis can be pivotal for potentially curative hematopoietic stem cell transplantation. Our work illustrates that cryptic splice variants may elude DNA-only sequencing and supports broad first-line use of transcriptome sequencing for children with undiagnosed diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549584PMC
October 2020

Epidemiology and Clinical Presentation of Children Hospitalized with SARS-CoV-2 Infection in Suburbs of Paris.

J Clin Med 2020 Jul 14;9(7). Epub 2020 Jul 14.

Service de Pédiatrie Générale, Centre Hospitalier de Rambouillet, 78120 Rambouillet, France.

Understanding the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and prognosis in children is a major issue. Children often present mild symptoms, and some severe forms require paediatric intensive care, with in some cases a fatal prognosis. Our aim was to identify the epidemiological characteristics, clinical presentation, and prognosis of children with coronavirus disease 2019 (Covid-19) hospitalized in Paris suburb hospitals. In this prospective, observational, multicentre study, we included children hospitalized in paediatric departments of Paris suburb hospitals from 23 March 2020 to 10 May 2020, during the national lockdown in France with confirmed SARS-CoV-2 infection (positive RNA test on a nasopharyngeal swab) or highly suspected infection (clinical, biological, and/or radiological data features suggestive for SARS-CoV-2 infection). A total of 192 children were included for confirmed ( = 157) or highly suspected ( = 35) SARS-CoV-2 infection. The median age was one year old (interquartile range 0.125-11) with a sex ratio 1.3:1. Fever was recorded in 147 (76.6%) children and considered poorly tolerated in 29 (15.1%). The symptoms ranged from rhinorrhoea (34.4%) and gastrointestinal (35.5%) to respiratory distress (25%). Only 10 (5.2%) children had anosmia and five (2.6%) had chest pain. An underlying condition was identified in almost 30% of the children in our study. Overall, 24 (12.5%) children were admitted to paediatric intensive care units, 12 required mechanical ventilation, and three died. For children in Paris suburbs, most cases of Covid-19 showed mild or moderate clinical expression. However, one-eighth of children were admitted to paediatric intensive care units and three died.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9072227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408757PMC
July 2020

Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors.

Bioorg Med Chem Lett 2020 08 12;30(16):127337. Epub 2020 Jun 12.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, 11562, Egypt. Electronic address:

A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f, 4d and 4a against PDE5 were similar to that of sildenafil (100%). These compounds exhibited potent relaxant effects on isolated rat cavernosum tissue with pEC values ranging from 8.31 to 5.16 µM. Pyrazolo[3,4-d]pyrimidin-7-one scaffolds have been rationally designed via consecutive molecular modelling studies prior to their synthesis and biological evaluation. In addition, the results of the pharmacophore-based virtual screening revealed that 1v0p_PVB might have promising activity as a PDE-5 inhibitor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2020.127337DOI Listing
August 2020

Design, synthesis, and cytotoxic screening of novel azole derivatives on hepatocellular carcinoma (HepG2 Cells).

Bioorg Chem 2020 08 3;101:103995. Epub 2020 Jun 3.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Novel azole derivatives 3-30 were designed, synthesized, and screened for their antitumor activity on HepG2 cell line. The cytotoxicity screening demonstrated that imidazolone 8 and triazoles 25 and 29 exhibited more potent cytotoxic activities by 1.21-, 4.75-, and 1.8-fold compared to Sorafenib (SOR). Furthermore, vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme inhibition assay declared that compounds 25 and 29 had inhibitory activity at the nanomolar concentration. Moreover, the tested compounds exhibited good β-tubulin (TUB) polymerization inhibition percentages. In addition, DNA flow cytometry analysis over HepG2 cells indicated that triazoles 25 and 29 demonstrated arrest at G and G/M phase of the cell cycle and induced apoptotic activity by increasing sub-G phase. Finally, mechanistic studies of the proapoptotic activities of compounds 8, 10, 11, 25, and 29 indicated that they induced upregulation of P53, Fas/Fas-ligand, and BAX/BCL-2 ratio expression that resulted in increasing the active caspase 3/7 percentages and trigger apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103995DOI Listing
August 2020

Loading characteristics of mechanical rib bolts determined through testing and numerical modeling.

Int J Min Sci Technol 2020 ;30(1):17-24

ITASCA Consulting Group, Minneapolis, MN 55401, USA.

Underground coal mines use mechanical bolts in addition to other types of bolts to control the rib deformation and to stabilize the yielded coal ribs. Limited research has been conducted to understand the performance of the mechanical bolts in coal ribs. Researchers from the National Institute for Occupational Safety and Health (NIOSH) conducted this work to understand the loading characteristics of mechanical bolts (stiffness and capacity) installed in coal ribs at five underground coal mines. Standard pull-out tests were performed in this study to define the loading characteristics of mechanical rib bolts. Different installation torques were applied to the tested bolts based on the strength of the coal seam. A typical tri-linear load-deformation response for mechanical bolts was obtained from these tests. It was found that the anchorage capacity depended mainly on the coal strength. Guidelines for modeling mechanical bolts have been developed using the tri-linear load-deformation response. The outcome of this research provides essential data for rib support design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274524PMC
January 2020

Movement Disorders Due to Selective Basal Ganglia Lesions with Uremia.

Can J Neurol Sci 2020 05;47(3):350-365

Department of Neurology and Psychiatry, Assiut University Hospital, Assiut, Egypt.

Background: Basal ganglia (BG) lesions are rarely reported in patients with uremia and may manifest by movement disorders. However, their exact incidence and pathogenesis have not been extensively studied. This study aimed to determine the frequency, types, risk variables (clinical, laboratory, and imaging), and manifestations of BG lesions with uremia and patients' neurologic outcomes.

Methods: This observational study included 70 adults (mean age: 45.87 ± 3.36 years; duration of uremia: 5.5 ± 1.5 years). They underwent extensive evaluations (clinical, laboratory, and neuroimaging) and had prospectively evaluated clinically every 3 months for 2 years. Repeated magnetic resonance imaging (MRI) brains were done to patients with movement disorders and correlated with their neurologic outcomes.

Results: BG lesions were found in 15 patients (21.4%) and 6 (8.6%) had movement disorders [Parkinsonism (n = 4), choreo-dystonia (n = 1) and dystonia (n = 1)] after the onset of uremia (mean = 10 months). There were no characteristic risk variables that distinguished patients with movement disorders from those without. Five developed movement disorders prior to the period of the study and one was de novo. The majority was females and had diabetes and higher frequencies of abnormal renal dysfunction, metabolic derangements, and white matter hyperintensities in MRIs. Movement disorders persisted in all patients despite the resolution of neuroimaging in three patients.

Conclusions: There is no clear threshold for renal failure to result in movement disorders due to BG lesions. The clinical outcome is variables depending on each patient's comorbidities and complications. Persistent neuronal damage (due to uremic toxins/metabolic/nutritional and ischemic/microvascular factors) has been suggested as the cause of poor neurologic outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/cjn.2020.29DOI Listing
May 2020

Synthesis and biological evaluation of pyrazolone analogues as potential anti-inflammatory agents targeting cyclooxygenases and 5-lipoxygenase.

Arch Pharm (Weinheim) 2020 Apr 7;353(4):e1900308. Epub 2020 Feb 7.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

New pyrazolone derivatives structurally related to celecoxib and FPL 62064 were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases (COXs) and 5-lipoxygenase (5-LOX) and their selectivity indices were calculated. The results showed that compounds 3f, 3h, 3l, and 3p have an excellent COX-2 selectivity index. Moreover, they showed potent 5-LOX inhibitory activity relative to celecoxib and zileuton, as positive controls. These promising candidates were further investigated for anti-inflammatory activity using the carrageenan-induced rat paw edema method and ulcerogenic liability. The results showed no ulceration, which implies their gastric safety profile. Moreover, these compounds were evaluated for prostaglandin (PGE2) production in rat serum. Molecular docking in the COX-2 and 5-LOX active sites was performed to rationalize their anti-inflammatory activities. Strong binding interactions and effective docking scores were identified. The results indicated that these derivatives are good leads for dual-acting COX-2/5-LOX inhibitors to be used as potent and safe anti-inflammatory agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.201900308DOI Listing
April 2020

New benzenesulfonamide scaffold-based cytotoxic agents: Design, synthesis, cell viability, apoptotic activity and radioactive tracing studies.

Bioorg Chem 2020 03 11;96:103577. Epub 2020 Jan 11.

Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, 12578 Cairo, Egypt. Electronic address:

A new series of thiazolidinone (5a-g), thiazinone (9a-g) and dithiazepinone (9a-g) heterocycles bearing a benzenesulfonamide scaffold was synthesized. Cytotoxicity of these derivatives was assessed against MCF-7, HepG2, HCT-116 and A549 cancer cell lines and activity was compared to the known cytotoxic agents doxorubicin and 5-FU where the most active compounds displayed better to nearly similar IC values to the reference compounds. For assessing selectivity, the most active derivatives against MCF-7, 5b, 5c and 5e, were also assessed against the normal breast cell line MCF-10 A where they demonstrated high selective cytotoxicity to cancerous cells over that to normal cells. Further, the effect of the most active compounds 5b-e on MCF-7 and HepG2 cell cycle phase distribution was assessed and the tested sulfonamide derivatives were found to induce accumulation of cells in the <2n phase. To further confirm apoptosis induction, caspase 8 and 9 levels in MCF-7 and HepG2 were evaluated before and after treatment with compounds 5b-e and were found to be significantly higher after exposure to the test agents. Since 5c was the most active, its effect on the cell cycle regulation was confirmed where it showed inhibition of the CDK2/cyclin E1. Finally, in vivo biodistribution study using radioiodinated-5c revealed a significant uptake and targeting ability into solid tumor in a xenograft mouse model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103577DOI Listing
March 2020

The effect of repetitive transcranial magnetic stimulation on cognitive impairment in Parkinson's disease with dementia: Pilot study.

Restor Neurol Neurosci 2020 ;38(1):55-66

Department of Neuropsychiatry, Assiut University Hospital, Assiut, Egypt.

Background: The exact mechanism of cognitive impairment in PD is not known. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible treatment for cognitive impairment and to treat the motor symptoms in Parkinson's disease (PD) where its effects seem additive to those of dopaminergic medications.

Objective: In this pilot study we investigated whether repeated sessions of rTMS have an effect on measures of cognitive impairment in patients with PD dementia.

Methods: 33 patients with PD dementia were randomly assigned sham or real rTMS (2000 pulses; 20 Hz; 90% RMT; 10 trains of 10 s with 25 s between each train) over the hand area of each motor cortex (5 min between hemispheres) for 10 days (5 days/week) followed by 5 booster sessions every month for 3 months. Assessments included the Unified Parkinson's Disease Rating Scale part III (UPDRS), Montreal Cognitive Assessment (MoCA); Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR); Memory and Executive Screening (MES) and Instrumental activity of Daily Living (IADL). Event related potentials (P300) and cortical excitability were measured before treatment and after the last session.

Results: There were no significant differences in the effects of rTMS between groups. Although rTMS improved motor function in the active group it had only a minor effect on two of the dementia rating scores (the MMSE and MoCA) but not the others (CDR and MES). There was also a reduction in the latency of the P300 in the active group.

Conclusions: rTMS over M1 is useful for motor function and may have a small positive effect on cognition. However, better approaches for the latter are necessary, may be require multisite rTMS to target both motor and frontal cortical region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/RNN-190956DOI Listing
February 2021

The EnteroBase user's guide, with case studies on transmissions, phylogeny, and core genomic diversity.

Genome Res 2020 01 6;30(1):138-152. Epub 2019 Dec 6.

EnteroBase is an integrated software environment that supports the identification of global population structures within several bacterial genera that include pathogens. Here, we provide an overview of how EnteroBase works, what it can do, and its future prospects. EnteroBase has currently assembled more than 300,000 genomes from Illumina short reads from , , , , , , and and genotyped those assemblies by core genome multilocus sequence typing (cgMLST). Hierarchical clustering of cgMLST sequence types allows mapping a new bacterial strain to predefined population structures at multiple levels of resolution within a few hours after uploading its short reads. Case Study 1 illustrates this process for local transmissions of serovar Agama between neighboring social groups of badgers and humans. EnteroBase also supports single nucleotide polymorphism (SNP) calls from both genomic assemblies and after extraction from metagenomic sequences, as illustrated by Case Study 2 which summarizes the microevolution of over the last 5000 years of pandemic plague. EnteroBase can also provide a global overview of the genomic diversity within an entire genus, as illustrated by Case Study 3, which presents a novel, global overview of the population structure of all of the species, subspecies, and clades within .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.251678.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961584PMC
January 2020

The usefulness of Veno-Arterial Extracorporeal Membranous Oxygenation in Patients with Cardiogenic Shock.

Open Access Maced J Med Sci 2019 Jun 15;7(11):1768-1773. Epub 2019 Jun 15.

Critical Care Department, Cairo University Hospitals, Cairo, Egypt.

Background: Venoarterial extracorporeal membranous oxygenation is a form of temporary mechanical circulatory support that gets as a salvage technique in patients with cardiogenic shock, we intended to evaluate the effect of (VA ECMO) support on hemodynamics and lactate levels in patients with cardiogenic shock.

Aim: The aim of our study is to detect the ability to introduce veno-arterial extracorporeal membranous oxygenation (VA ECMO) as a temporary extracorporeal life support system (ECLS) in our unit, demonstrate the role of ECMO in cardiogenic shock patients regarding improving hemodynamics and microcirculation, and demonstrate the complications and drawbacks in our first center experience regarding VA ECMO.

Material And Methods: This was a single-centre observational study that included 10 patients admitted with cardiogenic shock for which VA ECMO was used as mechanical circulatory support.

Results: The MAP increased after initiation of the support. It was 41.8 ± 9.3 mmHg and 59.5 ± 6.8 mmHg (P = 0.005). The use of VA ECMO support was associated with a statistically significant decrease in the base deficit (-10.6 ± 4.2 and -6.3 ± 7.4, P = 0.038). The serum lactate declined from 5.9 ± 3.5 mmoL/L to 0.6 ± 4.4 mmoL/L by the use of VA ECMO; a statistically significant change (P = 0.005).

Conclusions: We concluded that VA ECMO as mechanical support for patients with cardiogenic shock might improve mean arterial blood pressure, base deficit and lactate clearance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3889/oamjms.2019.547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614275PMC
June 2019

Outcome predictors of autologous hematopoietic stem cell transplantation in children with relapsed and refractory Hodgkin lymphoma: Single-center experience in a lower-middle-income country.

Pediatr Transplant 2019 09 4;23(6):e13531. Epub 2019 Jul 4.

Department of Pediatric Oncology and Stem Cell Transplantation Unit, Children Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.

Background: Children and adolescents with HL have excellent long-term survival exceeding 95% after combined modality treatment. However, about 20% will either relapse or have PRF. Salvage HDCT followed by AHSCT is considered to be the preferential treatment.

Objective: To describe the outcome (OS and EFS) and prognostic factors in pediatric patients with relapsed or refractory HL (r/rHL) who underwent AHSCT.

Methods: We retrospectively included 43 pediatric patients with r/rHL who underwent AHSCT from July 1, 2007, till December 31, 2016, at the Children's Cancer Hospital of Egypt. MAC regimen given was CMV.

Results: Of the whole cohort, 88.4% of patients achieved CR, while 11.6% had a positive PET scan prior to transplantation. The 3-year OS and EFS were 85% and 70.6%, respectively. The 3-year OS for patients > 10 years was 94% versus 65.5% for patients 10 years of age or younger (P = 0.046). There is strong tendency toward better 3-year OS for patients with negative PET scan as compared to those with positive PET scan before AHSCT, 89.4% vs 60%, respectively (P = 0.059). This tendency is also applicable when looking at the 3-year EFS for the two groups, 78.3% vs 40%, respectively (P = 0.069).

Conclusion: Poor predictors of OS were younger age and positive PET scan before AHSCT. The latter, along with single modality treatment before AHSCT, were poor predictors of EFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13531DOI Listing
September 2019

Qualitative and quantitative analysis of the uptake of lipoplexes by villous placenta explants.

Int J Pharm 2019 Aug 27;567:118479. Epub 2019 Jun 27.

Faculté de Pharmacie de Paris, Université Paris Descartes, 75006 Paris, France; Chemical and Biological Technologies for Health Unit (UTCBS), CNRS UMR8258, 75006 Paris, France; UTCBS, INSERM U1267, 75006 Paris, France.

Controlled distribution of a drug by its association to a nanocarrier is a promising approach for the treatment of pregnancy disorders such as preeclampsia. For this application, tracking both the nanocarrier and the drug is necessary to ensure the safety of both the mother and the foetus. This study reports a method to visualize and quantify the uptake of liposomal formulations in placental tissue using florescent labelling and appropriate analytical tools. Lipoplexes were labelled with a fluorescent lipid, DOPE-NBD while the encapsulated siRNA was fluorescently labelled with rhodamine. Lipoplexes were incubated with villous placenta explants, explants were imaged with confocal microscopy, then DOPE-NBD was extracted from the explant and quantified by HPLC. Qualitative evaluation by confocal microscopy showed the presence of lipoplexes and siRNA into the outer layer of the placental explants, the syncytiotrophoblast. For quantitative evaluation, an HPLC method for the quantification of fluorescent lipid DOPE-NBD in placental tissue was developed and validated. The developed method was applied to quantify the DOPE-NBD uptake in the placental tissue. Increased amounts of DOPE-NBD were detected in placental explants when increasing the incubation concentration of lipoplexes. This study provides a method to evaluate the interactions between liposomal formulation and the placental barrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2019.118479DOI Listing
August 2019

The Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Advancing Parkinson's Disease With Dysphagia: Double Blind Randomized Clinical Trial.

Neurorehabil Neural Repair 2019 06 10;33(6):442-452. Epub 2019 May 10.

2 UCL Queen Square Institute of Neurology, London, UK.

We investigate if rTMS has a therapeutic role in the treatment of dysphagia in patients with Parkinson's disease (PD). . Thirty-three patients with PD and dysphagia were randomly classified with ratio 1:2 to receive sham or real rTMS (2000 pulses; 20 Hz; 90% resting motor threshold; 10 trains of 10 seconds with 25 seconds between each train) over the hand area of each motor cortex (5 minutes between hemispheres) for 10 days (5 days per week) followed by 5 booster sessions every month for 3 months. Assessments included the Unified Parkinson's Disease Rating Scale part III (UPDRS), Instrumental Activities of Daily Living (IADL), and Arabic-Dysphagia Handicap Index (A-DHI) before, after the last session, and 3 months later. Video-fluoroscopy measures of pharyngeal transit time (PTT) and time to maximal hyoid elevation (H1-H2) were taken before and after the treatment sessions. . There were no significant differences between groups. There was a significant improvement on all rating scales (analysis of variance) after real rTMS with a significant time × group interaction. In particular, there was a significant and long-lasting (3 months) effect of time on all subitems of the A-DHI (functional, = .0001; physical, = .0001; emotional, = .02) but not in the sham group. This was associated with significant improvement in H1-H2 ( = .03) and PTT ( = .01) during solid swallows in the real rTMS but not the sham group. . Real rTMS improves dysphagia in PD as documented by A-DHI scores and by video-fluoroscopy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1545968319847968DOI Listing
June 2019

Outcome of orthotopic sigmoid versus ileal neobladder reconstruction.

Urol Ann 2019 Apr-Jun;11(2):204-210

Department of Urology, Faculty of Medicine, El-Fayoum University, El-Fayoum, Cairo, Egypt.

Introduction: Radical cystectomy with orthotopic urinary diversion is considered the gold standard for treatment of muscular invasive bladder cancer or high-risk nonmuscular invasive bladder cancer. The choice of orthotopic neobladder reconstruction depends on the clinical outcomes of it and should be planned with the patients, especially the risk of incontinence.

Methods: this study included 52 Egyptian patients underwent radical cystectomy and orthotopic neobladder reconstruction with sigmoid (25 patients) and ileal (27 patients) segments. Postoperative clinical outcomes between the sigmoid and ileal neobladder groups were compared.

Results: In the present study, 12 intraoperative complications (6 in each group) and 19 postoperative complications (17 in sigmoid and 15 in ileal group) occurred; however, there was no significant difference in the incidence of intraoperative and postoperative complications between both groups. There were no significant differences in the continence status and spontaneous voiding between both groups. There were no significant differences in maximal flow rate and voided volume between both groups. Night voiding frequency in the ileal neobladder patients was significantly smaller than sigmoid neobladder patients. Free flowery showed a significant difference of voiding time and volume in favor of sigmoid neobladder group. Maximum urethral pressure and urethral closing pressure were significantly higher in ileal neobladder group.

Conclusions: Both types of neobladder reconstruction resulted in comparatively satisfactory outcomes; however, the voiding function in sigmoid neobladder group appeared to be more favorable than that in ileal neobladder group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/UA.UA_137_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476219PMC
May 2019

Impact of Cognitive Dysfunction in the Middle East Depressed Patients: The ICMED Study.

Clin Pract Epidemiol Ment Health 2018 31;14:270-283. Epub 2018 Oct 31.

Psychiatric Departments, Sheikh Khalifa Medical City, Abu Dhabi, UAE.

Background: Major depressive disorder is a common condition with a high rate of recurrence, chronicity, and affecting economic burden, including disability in the workplace, which leads to negative consequences on both individuals and society.

Objectives: This study aimed to estimate the impact of cognitive dysfunction, as declared by the patient, on performing daily tasks/activities among patients with major depression disorder (MDD).

Methods: This investigation is based on multinational cross-sectional survey of 499 workers recruited from the Kingdom of Saudi Arabia (KSA) and United Arab Emirates (UAE). We assessed the severity of depression by Hamilton Depression Rating Scale (HDRS). Impact of Depression in the Workplace in Europe Audit (IDEA) survey and trial making test (TMT) parts A and B were used to assess the impact of cognitive dysfunction on performing daily tasks/activities in adult patients presented with MDD.

Results: A total of 499 persons were included in this study, aged 18-66 years, current workers and managers. Of them, 17.8% were normal (remitted), 22.4% were mildly depressed, 23.4% were moderately depressed, 8.6% were severely depressed, and 27.7% were very severely depressed at the time of the study according to HDRS. Common symptoms attributable to depression were low mode or sadness (89.8%), followed by insomnia (75.2%) and crying (70.9%). Of them, low mode or sadness was the most common factor affecting the work performance (90.2%). About 66.3% of participants diagnosed with depression by a doctor/medical professional. Awareness of the disease was recognizable by patients' managers in only 31.9% of the cases. Furthermore, 45.3% of cases had taken off work due to depression with mean duration of 38.7 (95% CI 37.7 to 39.7) days. The mean TMT parts A and B score were 69.2 (95% CI 66.3 to 72.2) and 126.6 (95% CI 121 to 132), respectively. Lastly, a significant positive correlation between the mean score for HDRS and TMT-A and B scores was observed.

Conclusion: Depression affects work productivity and work environment with negative consequences to countries' economy. Awareness of depression in the workplace in KSA and UAE is still suboptimal. The personal and societal burden of this issue cannot be neglected when we become aware of the proportion of affected people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1745017901814010270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407647PMC
October 2018

A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies.

Bioorg Chem 2019 03 5;84:399-409. Epub 2018 Dec 5.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

A new series of diamide functional compounds has been designed, synthesized and confirmed by spectroscopic methods and elemental analyses. All the synthesized compounds were evaluated for their antiproliferative activity on HepG2 cell line. Compounds 3k and 3l were proved to have potent anticancer activity equipotent or more potent than reference compound Combretastatin A-4. The results of DNA flow cytometry analysis demonstrated cell cycle arrest at G2/M phase. The extent of apoptosis induced by 3k and 3l was also determined. Moreover, the compounds produced a significant reduction in cellular microtubules for microtubule loss and potently inhibited the binding of [H]colchicine to tubulin. Compounds 3k and 3l were proved to upregulate expression of proteins triggering apoptosis, such as p53, Bax, and decreased Bcl-2 overexpression as well as increased the expression of effector caspase- 3/7.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2018.12.007DOI Listing
March 2019

Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine.

J Virol 2019 02 5;93(4). Epub 2019 Feb 5.

Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA

Ebolaviruses Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) cause human disease with high case fatality rates. Experimental monovalent vaccines, which all utilize the sole envelope glycoprotein (GP), do not protect against heterologous ebolaviruses. Human parainfluenza virus type 3-vectored vaccines offer benefits, including needle-free administration and induction of mucosal responses in the respiratory tract. Multiple approaches were taken to induce broad protection against the three ebolaviruses. While GP consensus-based antigens failed to elicit neutralizing antibodies, polyvalent vaccine immunization induced neutralizing responses to all three ebolaviruses and protected animals from death and disease caused by EBOV, SUDV, and BDBV. As immunization with a cocktail of antigenically related antigens can skew the responses and change the epitope hierarchy, we performed comparative analysis of antibody repertoire and Fc-mediated protective mechanisms in animals immunized with monovalent versus polyvalent vaccines. Compared to sera from guinea pigs receiving the monovalent vaccines, sera from guinea pigs receiving the trivalent vaccine bound and neutralized EBOV and SUDV at equivalent levels and BDBV at only a slightly reduced level. Peptide microarrays revealed a preponderance of binding to amino acids 389 to 403, 397 to 415, and 477 to 493, representing three linear epitopes in the mucin-like domain known to induce a protective antibody response. Competition binding assays with monoclonal antibodies isolated from human ebolavirus infection survivors demonstrated that the immune sera block the binding of antibodies specific for the GP glycan cap, the GP1-GP2 interface, the mucin-like domain, and the membrane-proximal external region. Thus, administration of a cocktail of three ebolavirus vaccines induces a desirable broad antibody response, without skewing of the response toward preferential recognition of a single virus. The symptoms of the disease caused by the ebolaviruses Ebola, Bundibugyo, and Sudan are similar, and their areas of endemicity overlap. However, because of the limited antigenic relatedness of the ebolavirus glycoprotein (GP) used in all candidate vaccines against these viruses, they protect only against homologous and not against heterologous ebolaviruses. Therefore, a broadly specific pan-ebolavirus vaccine is required, and this might be achieved by administration of a cocktail of vaccines. The effects of cocktail administration of ebolavirus vaccines on the antibody repertoire remain unknown. Here, an in-depth analysis of the antibody responses to administration of a cocktail of human parainfluenza virus type 3-vectored vaccines against individual ebolaviruses was performed, which included analysis of binding to GP, neutralization of individual ebolaviruses, epitope specificity, Fc-mediated functions, and protection against the three ebolaviruses. The results demonstrated potent and balanced responses against individual ebolaviruses and no significant reduction of the responses compared to that induced by individual vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.01845-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364037PMC
February 2019

Synthesis, Characterization and Cytotoxicity Evaluation of Some Novel Pyridine Derivatives.

Acta Chim Slov 2018 Dec;65(4):787-794

Reaction of isonicotinaldehyde with 2-cyanoacetohydrazide afforded (E)-2-cyano-N'-(pyridin-4-ylmethylene)acetohydrazide (1). Compound 1 was used as the precursor for the synthesis of novel pyridine derivatives by reaction with different arylidene malononitriles, malononitrile and acetylacetone to give pyridine derivatives 5a-e, 6 and 7, respectively. 4,4'-Bipyridine derivatives 9a-d were synthesized by a three-component reaction of isonicotinaldehyde, 2-cyanoacetohydrazide and activated nitriles 8a-d. Treatment of compound 9a with different aromatic aldehydes gave [1,2,4]triazolo[1,5-a]pyridine derivatives 11a-c. All reaction products were characterized by analytical and spectral data. For the novel compounds their bioactivity as antitumor agents was examined for in vitro cytotoxicity against HepG-2 and MCF-7. It was found that compounds 9a and 9b have high cytotoxic activity against both HepG-2 and MCF-7.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2018