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Preparation, <i>In-vitro, Ex-vivo</i>, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based <i>In Situ</i> Gel
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Background:

Lasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.

Objective:

This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.

Method:

Two successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by Kumar et al. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (Cmax), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5.

Result:

The results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, Tmax, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066 ± 242 ng/ml, 0.75 ± 0.05 h, 19616.86 ± 589 ng. h/ml, and 7975.67 ± 239 ng/ml, 1.0 ± 0.05 h, 17912.36 ± 537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09 ± 125 ng/ml, 2 ± 0.2 h, and 8852.27 ± 266 ng. h/ml, respectively. It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p < 0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula.

Conclusion:

NEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.

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Publication Date
Wed Jan 01 2020
Journal Name
Biochemical And Cellular Archives
EFFECT OF CHALCONE ON THE FORMATION OF BIOFILMS AND EXPRESSION OF VIRULENCE GENES IN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
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MRSA is one of the major pathogens in hospitals and the community, which have the ability to produce biofilm as a virulence factor, the impact of chalcone on biofilm formation, the synergism effect of chalcone and antibiotic in both in vitro and in vivo experiments, the gene expression of virulence genes (srtA, fnbA, fnbB) before and after treatment of it on MRSA biofilm cells in vitro, all these were the prime aims of this study. Chalcone at MBIC (20 μg/ml), significantly reduced the biofilm formation to 21.45% and at sub MBIC (15 μg/ml) to 36.58 %. While, Chalcone at MIC(5 μg/ml) reduced MRSA planktonic cells to 49.61%. Susceptibility of MRSA isolates against eight antibiotics showed that all isolates were sensitive to vancomycin and n

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Scopus
Publication Date
Tue Jun 15 2021
Journal Name
Al-academy
The authority of identification and alienation of existence in the theater of the oppressed: عبلة عباس خضير التميمي
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This research is represented by exploring the experience of "the theater of the oppressed" by (Augusto Boal) as an experiment that represents a different aesthetic pattern in the presentation of theatrical performance which is in contrast with the Aristotelian and Brechtian patterns, and as a result of the increasing problems of the individual in societies according to his needs and an attempt to express the suffering of human and the loss of his rights in general.
The research also tries to uncover the power of identification and the alienation of existence in the theater of the oppressed as that power, with its diversity of legal, legitimate, religious, political, economic and social capabilities has become a burden instead of being

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Publication Date
Sat Jun 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Freedom of movement of capital and its impact on the effectiveness of monetary policy In Iraq (2005-2016)
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The interest in the issue of capital movement as an economic phenomenon has increased because of its effects and effects and its ability to influence the economic balance and the effectiveness of monetary policy. All countries seek to attract capital and benefit from it because of its effects and results such as supporting economic development process and optimal allocation of economic resources. The problem of the financing gap that most countries suffer from, and others, but sometimes the movement of capital creates challenges for monetary policy makers in achieving their goals.

   After 2003, the Iraqi economy witnessed an openness and economic liberalization unlike previous years, which

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Publication Date
Sat Apr 15 2023
Journal Name
Iraqi Journal Of Science
Processing and interpretation of 3D seismic data of an oil field in central of Iraq using AVO techniques
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In this research, a qualitative seismic processing and interpretation is made up
through using 3D-seismic reflection data of East-Baghdad oil field in the central part
of Iraq. We used the new technique, this technique is used for the direct hydrocarbons
indicators (DHI) called Amplitude Versus Offset or Angle (AVO or AVA) technique.
For this purposes a cube of 3D seismic data (Pre-stack) was chosen in addition to the
available data of wells Z-2 and Z-24. These data were processed and interpreted by
utilizing the programs of the HRS-9* software where we have studied and analyzed
the AVO within Zubair Formation. Many AVO processing operations were carried
out which include AVO processing (Pre-conditioning for gathe

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Publication Date
Thu Sep 30 2021
Journal Name
Iraqi Journal Of Science
Detection of Serum Levels of IL-17 and CCL-5 in a Sample of Iraqi Pulmonary Tuberculosis Patients
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      Cytokines and chemokines are small-secreted proteins involved in many aspects of cell development, differentiation, and activation functions. A prominent characteristic of these molecules is their effect on the immune system in relation to the development of cell trafficking and immune tissues and organs. Furthermore, they play an important role in initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis-infected lungs. We aimed to evaluate the levels of interleukin -17 (IL-17) and the chemotactic chemokine (C-C motif) ligand 5 (CCL5) in the sera of pulmonary tuberculosis (PTB) patients. About 90 subjects were included, involving 5

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Publication Date
Sun Oct 06 2013
Journal Name
Journal Of Educational And Psychological Researches
Awareness of children 's rights from the perspective of parents and educators kindergarten in the city of Baghdad
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The subject of children's rights in the modern era of the priorities of educators , because the child in the community is the future , which is held by the hope which is the basis for society in the renaissance and progress so quickly communities to prove these rights through its various institutions and issued legislation and held numerous conferences and taking specialists the field of childhood Aatron aspects of this rights and Aasalunha including a benefit for children until tomorrow for the rights of children , psychological and social health and educational . Therefore, the current study focused on the awareness of parents and educators of children's rights as individuals most closely satisfying their needs and rights. The

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Publication Date
Wed Jul 01 2020
Journal Name
Indian Journal Of Forensic Medicine And Toxicology,
Effects of alcoholic extracts of cinnamomum zeylanicum and origanum majorana on expression of hly gene in escherichia coli
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Scopus (2)
Scopus
Publication Date
Thu Feb 01 2024
Journal Name
Iop Conference Series: Earth And Environmental Science
Processing and re-interpretation of gravity bouguer map of a selected area in the W-NW of Iraq
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Abstract<p>Geophysical data interpretation is crucial in characterizing the subsurface structure. The Bouguer gravity map analysis of the W-NW region of Iraq serves as the basis for the current geophysical research. The Bouguer gravity data were processed using the Power Spectrum Analysis method. Four depth slices have been acquired after the PSA process, which are: 390 m, 1300 m, 3040 m, and 12600 m depth. The gravity anomaly depth maps show that shallow-depth anomalies are mainly related to the sedimentary cover layers and structures, while the gravity anomaly of the deeper depth slice of 12600 m is more presented to the basement rocks and mantle uplift. The 2D modeling technique was used for </p> ... Show More
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Publication Date
Fri Nov 29 2013
Journal Name
Arabian Journal Of Geosciences
Cd, Ni, and Pb distribution and pollution assessment in roadside dust from Baghdad City and Western Iraqi Desert
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Publication Date
Sat Dec 31 2022
Journal Name
Al-kindy College Medical Journal
Thyroidectomy in elderly ; is it safe?
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Background: The prevalence of thyroid nodules rise with age and different data available about the risks of thyroid surgery in old age people. In general, old age could be a predictor of perioperative mortality and morbidity. The aim of this study is to prove if there is increased risk accompanying thyroidectomy in elderly patients.

Subjects and Methods: Prospective study of one surgeon of study sample undergoing thyroid surgery at Al-Kindy teaching hospital and Saint Raphael hospital .This study was including two groups; group (A) involved patients 65 years and older, group (B) involved patients below 65 years old who were subjected to thyroidectomy. Taking in consideration hist

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