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Therapeutic monitoring of Amikacin Regimen Associated Toxicity in Febrile neutropenic Pediatric Cancer Patients

Research Abstract

 

Aim of  work:

1-Evaluation of amikacin serum level in pediatric cancer patients with fever, neutropenia and impact of this level on the efficacy and toxicity of Amikacin.

2-Comparison between once versus twice daily regimens of amikacin will be done to know which regimen is most effective and less toxic.

Patients and methodology:

Inclusion Criteria:

1-Pediatric patients aged from 1-12 years.                                                           

2-patients with hematological malignancies admitted to South Egypt Cancer Institute,    Assiut University.                                                                                                                                  3-patients with normal renal and hearing function.

Exclusion Criteria:                                               

1-patients below one year.         

2-patients have renal or hearing dysfunction.                                                                                             

3-patients receive drugs which affect renal function.

Written informed consent was obtained from parents of the children. Patients with hematological malignancies admitted to South Egypt Cancer Institute, Assiut University to be treated empirically with intravenous amikacin for neutropenic fever, were participate in the study.

50 pediatric patients were randomly assigned to receive 15 mg/kg amikacin (amikacin salphate vail)   intravenously either once a day or divided in two equal doses every 12 h by 30 minute infusion, with maximum dose of 1 gm per day .

     Amikacin serum concentrations will analyzed at Pharmacokinetic Laboratory , South Egypt Cancer Institute.  Amikacin will be measured by means of homogeneous enzyme immunoassay using Viva Emit® assay (Siemens Healthcare Diagnostics, USA). Peak of amikacin concentrations will be obtained after one hour from starting intravenous infusion and concentrations will be obtained 8-12h after the last dose for all patients.                  

Renal function and hearing function will be assessed by measuring serum creatinine (Nephrotoxicity was defined as the increase of 0.5 mg/dl [50 lmol/L] from baseline value.)  and audiogram respectively before and after the treatment. Comparison between once versus twice daily regimens of amikacin will be done to know which regimen is most effective and less toxic.

 

Research Authors
Abdel-Azim Assi, Safaa A. and Aya Sayed
Research Date
Research Department
Research Journal
AS Pharmaceutical Sciences Journal

Effect of Ivabradine on Cognitive Functions of Rats with Scopolamine-induced Dementia

Research Abstract

Alzheimer’s disease is among the challenging diseases to social and healthcare systems because no treatment has been achieved yet. Although the ambiguous pathological mechanism underlying this disorder, ion channel dysfunction is one of the recently accepted possible mechanism. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in cellular excitability and synaptic transmission. Ivabradine (Iva), an HCN blocker, is acting on HCN channels, and is clinically used for angina and arrhythmia. The current study aimed to investigate the therapeutic effects of iva against scopolamine (sco) induced dementia. To test our hypothesis, Sco and Iva injected rats were tested for behavioural changes, followed by ELISA and histopathological analysis of the hippocampus. Induced dementia was confirmed by behavioural tests, inflammatory cytokines and oxidative stress tests and histopathological signs of neurodegeneration, multifocal deposition of congo red stained amyloid beta plaques and the decreased optical density of HCN1 immunoreactivity. Iva ameliorated the scopolamine-induced dysfunction, the hippocampus restored its normal healthy neurons, the amyloid plaques disappeared and the optical density of HCN1 immunoreactivity increased in hippocampal cells. The results suggested that blockage of HCN1 channels might underly the Iva therapeutic effect. Therefore, Iva might have beneficial effects on neurological disorders linked to HCN channelopathies.

Research Authors
Abdel-Azim Assi 1, Sara abdelnabi3, Abdelraheim Attaai2*, Rasha B. Abd-ellatief 1 1 Department of pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. Assi@aun.edu.eg. 1 Department of pharmacology, Faculty of Medicine, Assiut University,
Research Date
Research Department
Research Journal
Scientific Reports
Research Year
2022

Evaluation of The Possible Effect of Curcuminand Ginkgo biloba Extract Combination on Scopolamine-induced Cognitive Dysfunction in Rats

Research Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that shows multimodal symptoms such as progressive cognitive impairment along with changes in mood and behavior. The disease comprises various stages of severity, including pre-clinical AD, mild cognitive impairment (MCI), and AD dementia.

The present study is designed to explore the beneficial use of polyphenols from natural plants for management of AD, in comparison to conventional standard therapy. In addition, the potentiating effect of the herbal combination of ginkgo biloba and curcumin against scopolamine-induced AD-like alterations will be assessed. This will be accomplished by proposing six specific aims:

 

1- Demonstration of the effect of curcumin, GBE and their combination on cognitive performance (learning and memory) and on locomotor activity of scopolamine-demented rats (behavioral tests).

2- Evaluation of the effect of these compounds on oxidative stress in the hippocampus of these animals.

3- Investigation of the effect of these products on inflammatory biomarkers (cytokines) in the hippocampus of these animals.

4- Assessment of the accumulation of amyloid β-containing plaques in the hippocampus of animals treated with these compounds compared to non-treated animals.

5- Determination of the effect of these compounds on cholinesterase activity in the hippocampus of scopolamine-treated rats.

6- Examination of the histopathological changes in the hippocampus of treated animals compared to non-treated rats.

Research Authors
Abdel-AzimAssiو Magda Yosryو Mariam Amin Essmat Hamdan
Research Date
Research Department

Chronic exposure to tobacco smoke attenuates the sedative, analgesic and behavioral effects of cannabinoid and aminoalkylindole agonists (delta-9-tetrahydrocannabinol, CP55244 and WIN55212-2) in male mice and rats

Research Abstract

The CB1 cannabinoid receptor in brain mediates the behavioral effects of sedation, antinociception, short-term memory loss and muddled thinking. In animal studies, tobacco smoke as well as nicotine induce the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. This study examined the effects of prior exposure to tobacco smoke as well as nicotine on the behavioral effects of cannabinoid and aminoalkylindole agonists (delta-9-tetrahydrocannabinol, CP55244 and WIN55212-2) in male mice and rats. METHODS: Mice (male A/J strain, 5 weeks old ;N=70) and male Sprague-Dawley rats, 5 weeks old (N = 70) were exposed to tobacoo smoke in metabolic cages for 45 days. In addition, separate groups of animals (N=30) were injected daily with nicotine (the psychoactive component in tobacco, 1 mg/kg, i.p.) or vehicle for 45 days On test day, animals were injected with delta-9- tetrahydrocannabinol, CP55244 and WIN55212-2 (0.5, 2.0, or 5.0 mg/kg, i.p.) or vehicle The animals were evaluated regarding their performance in: 1. Open field method to test spontaneous locomotor activity. 2. Morris water maze test . 3. Radial-arm maze test. 4. Rota-rod test 5. Hot-plate and tail-Flick tests 6. Social interaction test. RESULTS: Chronic exposure to tobacco smoke and nicotine pretreatment
attenuated some of the behavioral effects induced by delta-9-tetrahydrocannabinol, CP55244 and WIN55212-2, which can be summarized as follows: (a) prior exposure to tobacoo smoke and nicotine attenuated the effect of the tested drugs on locomotor acvtivity, sedation but with no significant effect on social interaction. (b) prior exposure to tobacoo smoke and nicotine attenuated the effect of the tested drugs on pain and short-term memory. (c) Tobacoo smoke was somewhat more effective than nicotine in these tests, may be due to the presence of other active constituents in tobacoo smoke.
CONCLUSIONS: The ability of chronic tobacoo smoke and nicotine prior exposure to produce long-lasting changes that alter the effects of acute drug administration suggests that chronic tobacoo smoke and nicotine may induce neuroplastic changes that influence the subsequent response to cannabinoid drug exposure.

Research Authors
Abdel-Azim Assi, Nermin Assi and Allyn Howlett
Research Date
Research Department
Research File
Research Journal
the 2021 NIDA International Forum and the CPDD Annual Meeting.

The Antioxidant Effect of Selenium on Succinylcholine-related Myalgia After Adult Sinuscopies: Randomized Controlled Double-Blind Trial

Research Abstract

Background: Succinylcholine has a fast onset, short duration of action, and is considered the choice for rapid sequence intubation. However, it produces muscle stiffness and postoperative myalgia (POM) as adverse effects. We hypothesized that the antioxidant selenium might affect POM incidence and severity. Objectives: The study aimed to investigate the antioxidant effect of selenium (against free radicals’ release) in minimizing the frequency of succinylcholine-related POM, measured by the 4-point myalgia score. The severity of fasciculations and the postoperative analgesic profile were recorded. The correlation between fasciculations and POM was also observed. Study Design: A prospective randomized controlled double-blind clinical study. Setting: Assiut University Hospitals. Methods: The current study included 80 adult patients scheduled for sinuscopies and randomly assigned into 2 equal groups. Two hours before the induction of general anesthesia, patients in the control group received oral placebo tablets, while patients in the selenium group received oral selenium 200 µg. The primary outcome of this trial was the POM score at 24 hours. Secondary outcomes included the intensity of fasciculations, Numeric Rating Scale (NRS), rescue analgesic consumption, and adverse effects of the studied drugs. Results: Myalgia scores were significantly decreased after selenium administration throughout the follow-up period (P = 0.023). No significant difference was reported regarding the incidence or degree of fasciculations (P = 0.511). A mild correlation was noticed between fasciculations and POM with r = 0.176 and P < 0.061. The NRS values were significant between groups at 6 hours after the procedure. There were significant differences (P < 0.05) regarding postoperative supplement analgesia, time to the first rescue analgesia, and the mean total number of analgesic claims. Significant differences were recorded for potassium levels only 30 minutes and creatine kinase levels at 6 and 24 hours postoperatively. Limitations: This study was applied on a single surgical category and other types of surgical procedures may have an effect on outcomes. Additional larger sample size studies and various doses of selenium may help to validate our results. Selenium is quite a significant element of the enzymatic antioxidant process through glutathione peroxidase. We did not measure the glutathione peroxidase level in blood. Conclusions: Oral selenium effectively reduced the succinylcholine-induced postoperative myalgia. It prolonged the time to first required analgesia and decreased the analgesic consumption throughout the whole study period without affecting the hemodynamics or any serious adverse effects.

Research Authors
Mohamed F. Mostafa, MD1 , Ekram A. Osman, MD1 , Mahmoud M. Abo Elkasem, MSc1 , Mohamed Ismail Seddik, MD2 , and Ragaa Herdan, MD1
Research Date
Research Journal
Pain Physician
Research Pages
E743-E751
Research Rank
1
Research Vol
24(6)
Research Year
2021

Role of placental apoptosis in aflatoxin B1 induced fetal growth faltering

Research Authors
Khalid M. Mohany
Research Date
Research Department
Research Journal
BIOCHEM CAIRO 2014
Research Vol
BThe Annual Meeting of the Medical Biochemistry and Molecular Biology Department, Kasr Al Ainy Faculty of Medicine, Cairo University
Research Year
2014

Implementation of the Molecular Basis of Medicine Course at Unaizah College of Medicine (UCM), Qassim University, Saudi Arabia from Boonshoft School of Medicine (BSOM), Wright State University: Analysis of Student Performance in 2014–2015

Research Abstract

In 2013, BSOM and UCM in Saudi Arabia entered a partnership, one that would transfer the medical school curriculum from BSOM to UCM. All components of the curriculum including courses, learning materials, instructional methods (peer instruction sessions (PI), team based learning sessions), and examinations were transferred. In fall 2014, UCM initiated its first class of medical students who matriculated into the first year of the BSOM curriculum at UCM. One year 1 course, Molecular Basis of Medicine (MBM) is comprised of molecular biology, biochemistry, metabolism, and human genetics. Our goal was to compare directly final grades of the UCM and BSOM Med 1 students in MBM. Analysis of the grading showed that 92.7% of BSOM students (n=111) passed the course, compared to 91.6% of UCM students (n=70). When broken down by sex, 96.7 % of UCM men (n=30) passed, while 93% of BSOM men (n=57) passed. UCM women (n=40) had 87.8 % pass rate, compared to 92.6 % for BSOM women (n=54).The final course averages were 80.5% +/− 10 for UCM and 84.4% +/− 8.4 for BSOM students, suggesting that there is a similar outcome in the two countries using the same material. Women achieved scores of 78.3% +/− 11 at UCM while at BSOM, they scored at 83.6% +/− 8.7. Men averaged 82.1% +/− 10 at UCM and 85.1% +/− 8.0 at BSOM. However, the two institutions exhibited distinctly different results on exams; UCM students achieved 76.7 %+/− 9 average on exams, while BSOM students scored 82.6% +/− 8.9. Furthermore, UCM men achieved 79.6% +/− 10, while the women scored 74.5% +/− 9 as compared to BSOM men scoring 83.3 %+/− 9 and 81.9% +/− 9 for BSOM women. UCM faculty greatly enhanced student learning by initiating innovative teaching techniques for their students. UCM faculty devised PI based reviews prior to exams, assessed each examination result, and using guidelines established by the Saudi government and Qassim University, made adjustments to exams. The analyzed data to date suggest that there is no major difference in the final student grades for the first iteration of MBM between BSOM and UCM. The only observed difference between BSOM and UCM student achievement is that UCM students are stronger in the active learning portion of MBM and weaker in the examination portion of MBM than BSOM Med 1 students. In order to address this potential problem, the UCM faculty and administration have revamped the premed curriculum at Qassim University/UCM. More data analyses on MBM at both UCM and BSOM in the coming years will provide additional and more quantitative results on this unique partnership. The BSOM-UCM partnership is best exemplified by the MBM course, in which a team of dedicated team of faculty and administrators implemented a complete, well-established course from a fully accredited USA medical school in a new medical school in the Kingdom of Saudi Arabia despite being separated by 8000 miles in distance.

Research Authors
Lawrence J Prochaska,Fayig Elmigdadi,Heba Khader,Khalid Mohany,Walaa Fadda,Reham Aboukhalil,Daniel J Organisciak,John Paietta,Nicholas J Reo,Marvin J Miller,Gary J Onady,John Donnelly,Adil Altwairgi,Azzam Alkadi,Saleh Aldamegh,Dean Parmelee
Research Date
Research Department
Research Journal
The FASEB Journal
Research Pages
888.1-888.1
Research Publisher
The Federation of American Societies for Experimental Biology
Research Vol
30
Research Year
2016

The correlation between Aflatoxin B1 and Placental Apoptosis in Pregnant women with Intrauterine Growth Restriction

Research Abstract

Objective:  Egypt has one of the highest incidences of intrauterine fetal growth restriction (IUGR) around the world. In the current study, we tried to explore the effect of Aflatoxin B1 toxicity as a risk factor of IUGR and to determine the role of placental apoptotic indices in the pathogenesis of IUGR and their association with maternal risk factors as residency, working and exposure to smoking.

Materials and Methods:  A case-control study was done at Women Health Hospital; Assiut University, Egypt included 60 pregnant women with asymmetrical IUGR besides a control group of 40 normal pregnancies were selected. Maternal urine samples were obtained for measuring Aflatoxin B1 level by layer chromatography. Quantitative determination of human placental Bcl-2 and caspase-3 using a monoclonal antibody-based enzyme-linked immunosorbent assay kits were performed.

Results: The results showed that aflatoxin B1 positive cases in the IUGR group had significantly higher placental caspase-3 and lower placental Bcl-2 concentrations than those which were aflatoxin B1 negative (p<0.01). The levels of placental apoptotic indices were higher in working women who lived in urban areas and those exposed to cigarette smoke than non-working women who lived in rural areas and non-smokers.

Conclusions: Aflatoxin B1 may affect the fetal growth by increasing the placental apoptosis. These results may highlight the importance of aflatoxin B1 which may contribute to the complex etiology of IUGR. Placental apoptotic indices levels were significantly affected by maternal residency, working and exposure to smoking in pregnancies complicated with IUGR.

Research Authors
Ahmed M Abbas, Mona AH El-Baz, Omar M Shaaban, Khalid M Mohany, Thorya S El-Deeb, Amira M El-Noweihi
Research Date
Research Department
Research Journal
Thai Journal of Obstetrics and Gynaecology
Research Pages
104-116
Research Vol
24(2)
Research Website
https://doi.org/10.14456/tjog.2016.8
Research Year
2016
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