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      • SCOPUSSCIEKCI등재

        Chiari Type III : Experience of Outcome for 15 Cases

        Gabr, Mohamed,Elmataeshy, Mahmoud,Abdullah, Ahmed A. The Korean Neurosurgical Society 2022 Journal of Korean neurosurgical society Vol.65 No.6

        Objective : Chiari III malformations are extremely rare hindbrain malformations that are associated with a high early mortality rate, or severe neurologic deficits in the survivors. The treatment is early operative closure and cerebrospinal fluid diversion (CSF) shunting. Methods : We operated on 15 patients by repair and excision between July 2014 till June 2020 and retrospective data collection was done. Only one patient doesn't need ventriculoperitoneal (VP) shunt and the other 14 patients need a VP shunt. We described stepwise dissection and untethering of the cerebellum from the bony edge to regrowth and herniation of cerebellum again into this potential space and simple dural closure or repair with graft was done. Results : We started with VP in eight patients (53%) and the other seven patients (46.7%) started with excision and then six patients need VP shunt later on because four patients developed CSF leak and two patients developed increased high intracranial tension. Only four patients (26.7%) needed a blood transfusion. Conclusion : There are variations in the outcome and not all cases of Chiari malformation III will die and severe developmental delay is not a must. Proper management and repair carry a good prognosis.

      • SCOPUS

        Ethanol-induced PGE<sub>2</sub> up-regulates Aβ production through PKA/CREB signaling pathway

        Gabr, Amr Ahmed,Lee, Hyun Jik,Onphachanh, Xaykham,Jung, Young Hyun,Kim, Jun Sung,Chae, Chang Woo,Han, Ho Jae Elsevier/North Holland [etc.] 2017 Biochimica et biophysica acta Vol.1863 No.11

        <P><B>Abstract</B></P> <P>Ethanol abuse aggravates dementia-associated cognitive defects through the progression of Alzheimer's disease (AD) pathophysiology. Beta-site APP-cleaving enzyme 1 (BACE1) has been considered as a key regulator of AD pathogenesis by controlling amyloid beta peptide (Aβ) accumulation. In addition, previous studies reported that endoplasmic reticulum (ER) stress and neuroinflammation have been proposed in ethanol-induced neurodegeneration. Thus, we investigated the role of ER stress and PGE<SUB>2</SUB>, a neuroinflammation mediator, in the ethanol-stimulated BACE1 expression and Aβ production. Using the human-derived neuroblastoma cell line SK-N-MC, the results show that ethanol up-regulated BACE1 expression in a dose-dependent manner. Ethanol stimulated reactive oxygen species (ROS) production, which induced CHOP expression and eIF2α phosphorylation. PBA (an ER stress inhibitor) attenuated the ethanol-increased cyclooxygenase-2 (COX-2) expression and PGE<SUB>2</SUB> production. By using salubrinal (an eIF2α dephosphorylation inhibitor) or <I>EIF2A</I> siRNA, we found that eIF2α phosphorylation mediated the ethanol-induced COX-2 expression. In addition, COX-2-induced BACE1 up-regulation was abolished by NS-398 (a selective COX-2 inhibitor). And, PF-04418948 (an EP-2 receptor inhibitor) pretreatment reduced ethanol-induced PKA activation and CREB phosphorylation as well as ethanol-stimulated Aβ production. Furthermore, 14-22 amide (a PKA inhibitor) pretreatment or <I>CREB1</I> siRNA transfection suppressed the ethanol-induced BACE1 expression. In conclusion, ethanol-induced eIF2α phosphorylation stimulates COX-2 expression and PGE<SUB>2</SUB> production which induces the BACE1 expression and Aβ production via EP-2 receptor-dependent PKA/CREB pathway.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Ethanol induces BACE1 expression and Aβ production. </LI> <LI> Ethanol-produced ROS stimulates eIF2α phosphorylation and CHOP expression. </LI> <LI> ER stress enhanced by ethanol stimulates COX-2-mediated PGE2 production, which is critical for BACE1 expression. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • Free Paper Session : Liver 2 ; Management Of Bleeding Anorectal Varices In cirrhosis

        ( Mamdouh Gabr ) 대한소화기학회 2007 SIDDS Vol.9 No.-

        Background/Aims: Bleeding from anorectal varices (AVR) is a rare complication of portal hypertension in crirrhosis. Though rare, yet it`s usually massive and life threatening. No agreement has been reached on which could be the optimal therapeutic strategy for bleeding AVR. Therefore, this study was conducted to evaluate the efficacy and safety of endoscopic band ligation (EBL) in the treatment of 12 patients with lower gastrointestinal bleeding from ruptured AVR. Methods: Emergency colonoscopy was done within 24 hours of admission to confirm the diagnosis and thereafter EBL was done with a pneumatic band ligation device. A follow-up endoscopy was done one week after the initial haemostatic procedure searching for any complications. Results: Successful haemostasis was achieved in all patients (100%). The only complication observed was a clean base shallow post EBL ulcers in 6 patients (50%). Recurrent bleeding was observed in 2 patients (16.6%). Conclusions: The experience reported in the present study confirms the efficacy and safety of this haemostatic modality in the treatment of this rare and frequently fatal cause of lower gastrointestinal hemorrhage.

      • SCIESCOPUSKCI등재
      • KCI등재
      • KCI등재

        Mechanistic understanding of the effect of renal impairment on metformin oral absorption using computer simulations

        May Almukainzi,Ranih Gabr,Ghada Abdelhamid,Raimar Löbenberg 한국약제학회 2017 Journal of Pharmaceutical Investigation Vol.47 No.2

        The physiological parameters that describe the reasons behind metformin accumulation in renal failure patients are not fully understood. The effect of high creatinin level in these patients on the elimination of metformin is unknown. The objectives of this work were to (1) evaluate the utility of Physiologically based pharmacokinetic (PBPK) modeling to predict the plasma levels of metformin in healthy and renal impairment individuals (2) identify parameters that explain the observed plasma levels in renal impairment (3) investigate the correlation between creatinine levels and metformin elimination by MATE1 transporter assuming competitive inhibition on this transporter. All simulations were performed using a PBPK approach in GastroPlus™. The simulated data was compared to experimental data in healthy adults and renal failure patients, who received 850 mg metformin HCl. To investigate the effect of creatinin level on the elimination of metformin through MATE1 transporter, 0.35, 0.5, 1, 2, and 5 mg/dl of creatinine on the elimination of 10 μM metformin were investigated in human embryonic kidney (HEK293) and in MATE1 overexpressed HEK293 cell. Our model was able to predict metformin absorption in healthy and renal failure patients. The renal dysfunction model showed that a down-regulation of the MATE1 transporter in kidney and liver was necessary to explain the increase in drug concentration in these patients. However, the accumulation of creatinine in renal impairment patients could not be linked to the MATE1 down-regulation. Understanding the reasons for the increase in metformin blood concentrations can help in reducing the clinical studies and the side effects in these patients.

      • KCI등재

        Outcomes of Surgical Management of Metopic Synostosis : A Retrospective Study of 18 Cases

        Mohamed E. Elhawary,Mohammed Adawi,Mohamed Gabr 대한신경외과학회 2022 Journal of Korean neurosurgical society Vol.65 No.1

        Objective : To describe the surgical management and postoperative outcomes in infants with metopic synostosis. Methods : We conducted a 5 years retrospective chart review of patients who underwent surgical correction of metopic synostosis at two university hospitals in Egypt during the period between June 2014 and June 2019. The study is conducted to 18 children. The type of surgical procedures and postoperative outcomes were assessed in all patients. Results : Five cases (27.8%) underwent endoscopic-assisted suturectomy, 10 cases (55.6%) underwent craniofacial reconstruction, and three cases (16.6%) underwent open burring of the metopic ridge. Fifteen patients underwent one surgery and three patients (16.6%) who need second operation. Ten patients (55.6%) had class I Whitaker classification. Conclusion : Regardless of type of surgery, the outcomes of surgical correction of metopic synostosis are excellent with only a few patients require revision or develop major complications.

      • Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis

        Kim, D.I.,Lee, K.H.,Gabr, A.A.,Choi, G.E.,Kim, J.S.,Ko, S.H.,Han, H.J. Elsevier Biomedical Press 2016 Biochimica et biophysica acta, Molecular cell rese Vol.1863 No.11

        Mitochondrial dysfunction is known as one of causative factors in Alzheimer's disease (AD), inducing neuronal cell death. Mitochondria regulate their functions through changing their morphology. The present work was undertaken to investigate whether Amyloid β (Aβ) affects mitochondrial morphology in neuronal cells to induce apoptosis. Aβ treatment induced not only the fragmentation of mitochondria but also neuronal apoptosis in association with an increase in caspase-9 and -3 activity. Calcium influx induced by Aβ up-regulated the activation of Akt through CaMKII resulting in changes to the phosphorylation level of Drp1 in a time-dependent manner. Translocation of Drp1 from the cytosol to mitochondria was blocked by CB-124005 (an Akt inhibitor). Recruitment of Drp1 to mitochondria led to ROS generation and mitochondrial fission, accompanied by dysfunction of mitochondria such as loss of membrane potential and ATP production. ROS generation and mitochondrial dysfunction by Aβ were attenuated when treated with Mdivi-1, a selective Drp1 inhibitor. Furthermore, the sustained Akt activation induced not only the fragmentation of mitochondria but also the activation of mTOR, eventually suppressing autophagy. Inhibition of autophagic clearance of Aβ led to increased ROS levels and aggravating mitochondrial defects, which were blocked by Rapamycin (an mTOR inhibitor). In conclusion, sustained phosphorylation of Akt by Aβ directly activates Drp1 and inhibits autophagy through the mTOR pathway. Together, these changes elicit abundant mitochondrial fragmentation resulting in ROS-mediated neuronal apoptosis.

      • KCI등재

        Highway Sustainability Factors: Holistic and Social Network Analyses

        Mohamed O. Rageh,Alaa R. Gabr,Sherif M. El-Badawy,Emad E. Elbeltagi 대한토목학회 2023 KSCE Journal of Civil Engineering Vol.27 No.11

        This study provides a holistic list of factors that affect highway sustainability (HWS) and determines the most significant factors throughout the triple-bottom-line of sustainability. Previous studies analyzed many factors related to sustainability performance in highway projects during their life cycle, whereas the social sustainability aspects were commonly ignored. In addition, there is imperative to consider the Sustainable Development Goals (SDGs) of highway projects in local and global future visions. On the other hand, the infrastructure rating systems specified different thresholds to achieve sustainable highways. Thus, this study analyzed published articles, SDGs, and infrastructure rating systems to extract the most important factors affecting HWS. A content analysis was conducted to specify the most relevant publications in HWS, which are strongly related to the research keywords. According to the content analysis, 150 articles out of 6,422 were selected for further investigation. Social Network Analysis (SNA) analyzed and ranked 224 factors that were extracted from the aforementioned sources to determine the factors of utmost importance. We found that 78 factors out of 224 are of paramount influence on HWS. Finally, the evaluation of the most widely used infrastructure rating systems revealed a shortage in the common factors affecting the HWS.

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