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1.
Biomed Chromatogr ; 35(5): e5048, 2021 May.
Article in English | MEDLINE | ID: mdl-33314205

ABSTRACT

A robust and rapid UPLC-MS/MS method has been developed, optimized and validated for determination of amlodipine (AML), indapamide (IND) and perindopril (PRN) in human plasma. A positive electrospray ionization mode was used in a Xevo TQD LC-MS/MS instrument. A single sample preparation step using extraction technique was applied to extract the three analytes from plasma samples. There was no need to extract indapamide from blood samples in a further step. Extraction of the three drugs and internal standards was done using a solvent mixture composed of methyl tertiary butyl ether, dichloromethane and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC HSS C18 (100 × 2.1 mm, 1.7 µm) column. Ammonium acetate and methanol, pumped at a flow rate of 0.3 ml/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.2-15 ng/ml for AML, 0.5-50 ng/ml for IND and 0.5-120 ng/ml for PRN. Accuracy and precision were estimated and found to be within the acceptable ranges. The rapid chromatography permits analysis of many samples per batch, making the method suitable for clinical and pharmacokinetic investigations. The developed and validated method was applied to estimate AML, IND, and PRN in a fasting bioequivalence study in healthy human volunteers.


Subject(s)
Amlodipine , Antihypertensive Agents , Chromatography, High Pressure Liquid/methods , Indapamide , Perindopril , Tandem Mass Spectrometry/methods , Adult , Amlodipine/blood , Amlodipine/pharmacokinetics , Antihypertensive Agents/blood , Antihypertensive Agents/pharmacokinetics , Humans , Indapamide/blood , Indapamide/pharmacokinetics , Limit of Detection , Middle Aged , Perindopril/blood , Perindopril/pharmacokinetics , Specimen Handling , Therapeutic Equivalency
2.
Biomed Chromatogr ; 35(7): e5098, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33606892

ABSTRACT

A novel, simple and rapid UPLC-MS/MS method was developed and validated for determination of favipiravir (FAV) in human plasma. Lamivudine was used as an internal standard (IS). The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Precipitation with acetonitrile was used in sample preparation as it gives relatively cleaner plasma samples. The prepared samples were chromatographed using an Acquity UPLC® HSS C18 (100 × 2.1 mm, 1.8 µm) column. The mobile phase was composed of ammonium formate and methanol in a gradient mode that was pumped at a flow rate of 0.35 ml/min. The developed method was validated as per the FDA guidelines and linearity was in the range of 0.25-16 µg/ml for FAV. The intra- and inter-day precision and accuracy results were within the acceptable limits. A run time of 4.5 min and a low quantification limit of FAV allowed the application of the developed method for the determination of FAV in a bioequivalence study in healthy human volunteers.


Subject(s)
Amides/blood , Chromatography, High Pressure Liquid/methods , Pyrazines/blood , Tandem Mass Spectrometry/methods , Adult , Amides/chemistry , Amides/pharmacokinetics , Female , Humans , Limit of Detection , Male , Middle Aged , Pyrazines/chemistry , Pyrazines/pharmacokinetics , Reproducibility of Results , Therapeutic Equivalency , Young Adult
3.
Biomed Chromatogr ; 32(7): e4224, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29498757

ABSTRACT

A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 µm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers.


Subject(s)
Amlodipine/blood , Atorvastatin/blood , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Adolescent , Adult , Amlodipine/chemistry , Amlodipine/pharmacokinetics , Atorvastatin/chemistry , Atorvastatin/pharmacokinetics , Humans , Linear Models , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Therapeutic Equivalency , Young Adult
4.
Biomed Chromatogr ; 32(11): e4347, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30047564

ABSTRACT

A novel and sensitive LC-MS/MS method was developed, optimized and validated for quantification of sofosbuvir (SOF) and velpatasvir (VEL) in human plasma using ledipasvir as an internal standard (IS). Sample preparation was done using acetonitrile for precipitation of plasma proteins. Chromatographic analysis was done on an Acquity UPLC BEH C18 column using 0.1% formic acid and acetonitrile as a mobile phase. The Xevo TQD LC-MS/MS system was run with electrospray ionization mode. The developed method was optimized and then validated according to the US Food and Drug Administration guidelines. Linearity was found to be in the range of 0.25-3500 ng/mL for SOF and 1-1000 ng/mL for VEL. A short run time of 1.5 min allows swift analysis of many plasma samples per day. The developed method was successfully utilized for estimating both SOF and VEL in the plasma of healthy human volunteers participated in a bioequivalence study.


Subject(s)
Carbamates/blood , Chromatography, High Pressure Liquid/methods , Heterocyclic Compounds, 4 or More Rings/blood , Sofosbuvir/blood , Tandem Mass Spectrometry/methods , Adult , Carbamates/pharmacokinetics , Female , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Humans , Linear Models , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Sofosbuvir/pharmacokinetics , Therapeutic Equivalency , Young Adult
5.
Med Teach ; 38(10): 1017-1024, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27008548

ABSTRACT

BACKGROUND: The Faculty of Medicine at the American University of Beirut implemented a new medical curriculum, which included 90 team-based learning (TBL) sessions in years 1 and 2 of medical school. METHODS: A validated team performance scale (TPS) and peer evaluation of communication skills, professionalism and personal development were collected at different time points during the two years. Grades on the individual and group readiness assurance tests and an evaluation form were collected after every TBL session. RESULTS: Students generally positively evaluated most TBL sessions as promoters of critical thinking and appreciated the self-learning experience, though they preferred and had better individual grades on those that entailed preparation of didactic lectures. There was a sustained and cumulative improvement in teamwork skills over time. Similar improvement was noted with peer evaluations of communication skills, professionalism, and personal development over time. CONCLUSIONS: This is the first report about such a longitudinal follow-up of medical students who were exposed to a large number of TBL sessions over two years. The results support the suggestion that TBL improves medical students' team dynamics and their perceived self-learning, problem solving and communication skills, as well as their professionalism and personal development.


Subject(s)
Attitude , Education, Medical, Undergraduate/methods , Group Processes , Learning , Problem-Based Learning/methods , Students, Medical/psychology , Cooperative Behavior , Curriculum , Educational Measurement , Female , Humans , Lebanon , Male , Models, Educational , Peer Group , Schools, Medical
6.
Environ Toxicol Pharmacol ; 105: 104344, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38103810

ABSTRACT

Two hundred and twenty subjects were recruited while undergoing cardiac catheterization. AHRR cg05575921 methylation was shown to be significantly decreased in ever smokers compared to never smokers (Mean± SD = 64.2 ± 17.2 vs 80.1 ± 11.1 respectively; P < 0.0001). In addition, higher urinary levels of 2-OHNAP and 2-OHFLU were significantly associated with more AHRR cg05575921 hypomethylation, even after correcting for smoking (ß[95%CI]= -4.161[-7.553, -0.769]; P = 0.016 and -5.190[-9.761, -0.618]; P = 0.026, respectively) but not 1-OHPYR (ß[95%CI]= -3.545 [-10.935, 3.845]; P = 0.345). Additionally, hypomethylation of AHRR ROI was significantly associated with obstructive coronary artery disease (CAD) after adjusting for smoking, age, sex, diabetes and dyslipidemia (OR [95%CI] = 1.024[1.000 - 1.048]; P = 0.046). Results of this study necessitate further validation to potentially consider clinical incorporation of AHRR methylation status as an early predictive biomarker for the potential association between ambient air pollution and CAD.


Subject(s)
Air Pollution , Coronary Artery Disease , Hydrocarbons, Aromatic , Humans , Coronary Artery Disease/genetics , Biomarkers , DNA Methylation , Repressor Proteins/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics
7.
Drug Res (Stuttg) ; 73(6): 349-354, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37094796

ABSTRACT

Favipiravir is an antiviral drug used to treat influenza and is also being investigated for the treatment of SARS-CoV-2. Its pharmacokinetic profile varies depending on ethnic group. The present research examines the pharmacokinetic features of favipiravir in healthy male Egyptian volunteers. Another goal of this research is to determine the optimum dissolution testing conditions for immediate release tablets. In vitro dissolution testing was investigated for favipiravir tablets in three different pH media. The pharmacokinetic features of favipiravir were examined in 27 healthy male Egyptian volunteers. The parameter "AUC0-t" vs. percent dissolved was used to develop level C in vitro in vivo correlation (IVIVC) to set the optimum dissolution medium to achieve accurate dissolution profile for favipiravir (IR) tablets. The in vitro release results revealed significant difference among the three different dissolution media. The Pk parameters of twenty-seven human subjects showed mean value of Cpmax of 5966.45 ng/mL at median tmax of 0.75 h with AUC0-∞ equals 13325.54 ng.h/mL, showing half-life of 1.25 h. Level C IVIVC was developed successfully. It was concluded that Egyptian volunteers had comparable Pk values to American and Caucasian volunteers, however they were considerably different from Japanese subjects. AUC0-t vs. % dissolved was used to develop level C IVIVC to set the optimum dissolution medium. Phosphate buffer medium (pH 6.8) was found to be the optimum dissolution medium for in vitro dissolution testing for Favipiravir IR tablets.


Subject(s)
COVID-19 , Humans , Male , Egypt , Area Under Curve , SARS-CoV-2 , Tablets , Volunteers , Solubility , Healthy Volunteers
8.
PLoS One ; 18(10): e0287844, 2023.
Article in English | MEDLINE | ID: mdl-37874832

ABSTRACT

Cardiovascular diseases are increasing at an alarming rate worldwide, reaching epidemic proportions in countries of the Eastern Mediterranean Region, including Lebanon. Despite the growing number of patients suffering from cardiovascular diseases in Lebanon, there is scarce data on whether cardiac patients adhere to therapeutic dietary guidelines, drug prescriptions, and physical activity recommendations and whether such adherence differs according to sociodemographic, lifestyle, or psychosocial characteristics. A cross-sectional study was conducted among 367 Lebanese adult cardiovascular disease patients admitted for hospitalization at various hospital sites in Lebanon. Electronic medical records and a multi-component questionnaire were used to collect information on patients' characteristics. Dietary assessment was performed using a culture-specific validated food frequency questionnaire, and physical activity levels were assessed using the international physical activity questionnaire (IPAQ). Mental well-being was assessed based on the validated five-item well-being index (WHO-5), and drug adherence was evaluated using the Morisky medication adherence scale (MMAS-8). The majority of the patients were males (67.8%), overweight or obese (74%), smokers (62.1%), and unemployed or retired (54.5%). Almost 35% of the patients were lonely, and nearly one fourth were at a high risk of poor mental health. Approximately 43%, 70%, and 52% of the patients were found to have poor adherence to diet, drug, and physical activity recommendations, respectively. A lower sense of mental well-being was a significant predictor of low dietary and drug adherence. Surprisingly, overweight and obesity were associated with higher odds of dietary adherence. Male gender was positively associated with physical activity while loneliness was inversely associated with physical activity. This study showed that adherence to diet, drug, and physical activity recommendations was low in this patient population and identified several non-clinical characteristics that may affect adherence. These findings highlighted the need for considering patients' psychosocial characteristics in the treatment of patients with cardiovascular diseases.


Subject(s)
Cardiovascular Diseases , Adult , Humans , Male , Female , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Overweight/epidemiology , Lebanon/epidemiology , Cross-Sectional Studies , Diet , Obesity/epidemiology , Exercise
9.
Hum Resour Health ; 10: 15, 2012 Jul 10.
Article in English | MEDLINE | ID: mdl-22780903

ABSTRACT

BACKGROUND: We recently proposed that Lebanon could become a regional 'academic hub' through the repatriation of emigrated Lebanese physicians who would then provide clinical services in the Arab Gulf region on a locum tenens basis. The objectives of this study were to assess the willingness of Lebanese medical graduates practicing in the United States of America to relocate to Lebanon and the Arab Gulf region and to explore the factors associated with this willingness. METHODS: In 2009 we surveyed Lebanese medical graduates practicing medicine in the United States. The questionnaire included questions about their willingness to relocate to Lebanon and to the Arab Gulf region and the associated timeframes. The questionnaire also included questions about family factors. We linked responders' answers to their personal, educational, and practice characteristics provided by the American Medical Association Physicians' Dataset. We conducted both descriptive and regression analyses. RESULTS: A total of 286 physicians participated in the survey (57% response rate). A majority (61%) was willing to relocate to Lebanon (51% possibly, 10% definitely). A third (33%) were willing to relocate to the Arab Gulf region (31% possibly, 2% definitely). About half (54%) were willing to relocate to Lebanon as a base for clinical missions to the Arab Gulf region (49% possibly, 5% definitely). Willingness to relocate to Lebanon was independently associated with Lebanese citizenship and the birthplace of the spouse being Lebanon, and inversely associated with US citizenship. Willingness to relocate to the Arab Gulf region was independently associated with being board certified, and inversely associated with being married, the age of the oldest child, and practicing in direct patient care. Willingness to relocate to Lebanon as a base was not independently associated with any factor. CONCLUSIONS: The findings of this study support the feasibility of the proposal of Lebanon becoming a regional 'academic hub'. Future research should explore other factors important for the feasibility of the proposal as well as actual relocation.

10.
Sci Rep ; 12(1): 21563, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36513746

ABSTRACT

Urinary podocin and nephrin mRNAs (podocyturia), as candidate biomarkers of endothelial/podocyte injury, were measured by quantitative PCR in Type II diabetics with normal albumin excretion rates (AER) at baseline, at 3-4 years, and at 7 years. Development of cardiovascular disease (CVD) was collected as outcome. Visit 1 podocyturia was significantly higher in subjects who subsequently developed CVD versus those who did not. Visit 1 AER terciles exhibited similar time to CVD, in contrast with stepwise and substantial increases in CVD events predicted by Visit 1 podocyturia terciles. Covariate-adjusted hazard ratios were highest for podocin, intermediate for nephrin mRNAs, and lowest for AER. Podocyturia was also measured in patients with and without significant coronary obstruction, and in 480 normoalbuminuric subjects at the enrolment visit to the Multi-Ethnic Study of Atherosclerosis (MESA). Podocyturia > 3 × 106 copies was associated with presence of obstructive coronary artery disease. In the MESA population, Visit 1 podocyturia was significantly higher in men, subjects with elevated BMI, and those with Type II DM. Conclusions: Podocyturia may be an earlier predictor of cardiovascular events than moderate albuminuria; it is significantly higher in patients with obstructive coronary artery disease, and in subjects with established risk factors for CVD.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Coronary Artery Disease , Podocytes , Male , Humans , Biomarkers , Risk Factors
12.
BMJ Open ; 11(10): e050957, 2021 10 19.
Article in English | MEDLINE | ID: mdl-34667007

ABSTRACT

INTRODUCTION: Alterations in linear and non-linear parameters of beat-to-beat blood pressure variability (BPV) have been shown to predict disease prognosis and distinguish between risk categories in various pathological conditions, independently of average blood pressure levels. Obesity places subjects at elevated risk of vascular diseases, including hypertension, resulting in serious cardiac, respiratory and cerebral events. However, little is known about the status of vascular dynamics in obese and morbidly obese adults. METHODS AND ANALYSIS: In this present quasi-experimental longitudinal study, changes in beat-to-beat BPV, using continuous, non-invasive blood pressure monitoring, in obese subjects undergoing bariatric surgery are characterised. The capacity of linear and non-linear measures of BPV to detect differences between hypertensive, prehypertensive and normotensive obese subjects prebariatric and postbariatric surgery are tested. Additionally, potential correlations between beat-to-beat BPV and age, body mass index, gender and comorbidities will be investigated. In parallel, the impact of the unsteady fluctuations of beat-to-beat blood pressure on the dynamic stresses imparted by blood flow on blood vessel walls will be explored. We expect to find altered BPV profiles in hypertensive and prehypertensive subjects as compared with normotensive subjects. We also expect to see differential normalisation in BPV profiles between hypertensive, prehypertensive and normotensive subjects over time. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board at the American University of Beirut (IRB ID: BIO-2018-0040). Study results will be made available to the public through publications in peer-reviewed journals and conference papers and/or presentations.


Subject(s)
Bariatric Surgery , Hypertension , Obesity, Morbid , Adult , Blood Pressure , Humans , Longitudinal Studies , Obesity, Morbid/surgery , Weight Loss
13.
Environ Pollut ; 272: 115967, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33176945

ABSTRACT

In Lebanon, previous studies have indicated an onset of cardiovascular diseases 12 years earlier than in other parts of the world, suggesting the presence of additional risk factors specific to Lebanon. Measurements of airborne particles in Lebanon surpass the recommendations of the World Health Organization by over 150%. This study examined the association between obstructive coronary artery disease (CAD), assessed by a novel marker calculated from coronary catheterization, and markers of air pollution, specifically polycyclic aromatic hydrocarbons (PAHs), in a cohort of 258 patients seen at the American University of Beirut Medical Center since 2014. The concentrations of four types of hydroxylated polycyclic aromatic hydrocarbons (OHPAHs), 2-OHNAP, 2-OHFLU, 3-OHPHE, and 1-OHPYR, were measured in the urine samples of these patients using high performance liquid chromatography coupled with fluorescence detector. Results showed that the OHPAH concentrations were higher than what was reported in high-income countries and, most notably, the levels for non-smokers in this study were higher than those of smokers and some occupational workers in other countries. This implies that patients were exposed to high levels of PAHs, which originate from combustion sources. In particular, 1-OHPYR showed a significant association with presence of obstructive CAD, even after adjusting for covariates like age, sex, and diabetes. Smokers or not, this association has implications for public health and calls for urgent need to pass regulations to reduce the emissions of PAH sources, such as cars, diesel generators, and incinerators.


Subject(s)
Coronary Artery Disease , Polycyclic Aromatic Hydrocarbons , Biomarkers , Chromatography, High Pressure Liquid , Coronary Artery Disease/epidemiology , Humans , Lebanon
14.
Nephrol Dial Transplant ; 25(12): 3962-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20525974

ABSTRACT

BACKGROUND: Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years' detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. METHODS: Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents' consanguinity were recorded when feasible. RESULTS: The mean age at renal biopsy was 36.76 ± 20 years (range 1-84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). CONCLUSIONS: Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population.


Subject(s)
Christianity , Consanguinity , Islam , Kidney Diseases/ethnology , Kidney Diseases/epidemiology , Kidney/pathology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Biopsy , Child , Child, Preschool , Female , Glomerulonephritis/epidemiology , Glomerulonephritis/ethnology , Glomerulosclerosis, Focal Segmental/epidemiology , Glomerulosclerosis, Focal Segmental/ethnology , Health Surveys , Humans , Infant , Lebanon/epidemiology , Male , Middle Aged , Prevalence , Retrospective Studies , Young Adult
15.
BMC Health Serv Res ; 10: 167, 2010 Jun 16.
Article in English | MEDLINE | ID: mdl-20565706

ABSTRACT

BACKGROUND: Lebanon suffers from a large scale emigration of physicians coupled with an oversaturation of the physician job market. Lebanon is currently witnessing an expansion of its medical education capacity with the establishment of new private medical schools, raising the fears of a worsening market oversaturation. DISCUSSION: The neighboring Arabian Gulf countries are suffering from a serious shortage of clinicians and academicians. In spite of their enormous investments in educational, clinical and research collaborative initiatives with some of the most renowned North American medical schools and institutions, their ability to recruit and retain highly qualified clinicians and academicians remains a major challenge. Lebanese universities have the opportunity to establish triangular collaborations with the Gulf regional medical centers and their North American partners. They could achieve this goal by tapping into the globalized and high quality Lebanese physician workforce and consequently regionalize healthcare delivery in the Middle East. SUMMARY: By recruiting its globalized and high quality physician workforce to establish collaborations with the Gulf regional, Lebanon could become a regional "academic hub".


Subject(s)
Emigration and Immigration , Physicians/supply & distribution , Regional Health Planning , Education, Medical , Humans , International Cooperation , Lebanon , Schools, Medical
16.
J Med Educ Curric Dev ; 7: 2382120520953106, 2020.
Article in English | MEDLINE | ID: mdl-32923674

ABSTRACT

OBJECTIVE: The American University of Beirut Faculty of Medicine follows the American model of medical education. In 2013-2014, a carefully designed new curriculum replaced the previous, largely traditional curriculum, and aimed to improve student wellbeing, upgrade the learning environment, enhance student empathy, and counter the negative influences of the hidden curriculum. This longitudinal study assessed the effectiveness of the new curriculum in those domains over a period of 7 years. METHODS: Three cohorts of medical students anonymously filled a paper-based survey at the end of years 1, 2, 3, and 4 of the 4-year curriculum. These included the Class of 2016, the last batch of students who followed the old curriculum, and 2 cohorts that followed the new curriculum (Class of 2017 and Class of 2019). The perceived learning environment was assessed by the Dundee Ready Education Environment Measurement survey; the student's empathy was assessed by the Jefferson Scale of Physician Empathy-Student version; and the hidden curriculum was examined using a locally developed survey. RESULTS: The scores on the learning environment survey were significantly higher among the cohorts following the new curriculum relative to those following the old curriculum. Similar significant results appeared when looking at each of the subscales for the learning environment. The students' empathy scores were also significantly higher in both cohorts of the new curriculum when compared with the old curriculum. Nevertheless, there was a significant decrease in empathy in both third and fourth years relative to second year. The new curriculum also improved aspects of the students' perceptions and responses to the hidden curriculum. CONCLUSION: In conclusion, a well-planned and well-researched curricular intervention, based on sound educational theories, practices, and standards can indeed transform the learning environment, as well as the attitudes, values, and experiences of medical students.

17.
FASEB J ; 21(8): 1665-74, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17317725

ABSTRACT

Macrophage cyclooxygenase-2 (COX-2) plays an important role in prostaglandin E2 and thromboxane A2 production. Statins are inhibitors of HMG CoA (3-Hydroxy-3-methylglutaryl coenzyme A) reductases and cholesterol synthesis, which block the expression of several inflammatory proteins independent of their capacity to lower endogenous cholesterol. In the present study, we investigated the effect of simvastatin and mevastatin on COX-2 induction in human monocytic cell line U937 and analyzed the underlying mechanisms. Pretreatment of U937 cells with simvastatin or mevastatin for 24 h resulted in a significant reduction in the lipopolysaccharide (LPS)-dependent induction of prostaglandin E2, thromboxane A2 synthesis, and COX-2 expression. Mevalonate, the direct metabolite of HMG CoA reductase, and farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, intermediates of the mevalonate pathway, significantly reversed the inhibitory effect of statins on COX-2. An inhibitor of geranylgeranyl transferases, GGTI-286 mimicked the effect of statins on COX-2 expression. Cytonecrotic factor-1 increased LPS-dependent expression of COX-2. Treatment of cells with NSC 23766, an inhibitor of Rac, which we demonstrated to block Rac 2 activation, resulted in an inhibition of the LPS-dependent expression of COX-2. Whereas no effect was obtained with RhoA/C blocker, C3 exoenzyme. Gel retardation experiments and NFkappaB-p65 transcription factor assay showed that simvastatin and NSC 23766 decrease significantly NF-kappaB complex formation. In macrophages, the antiinflammatory effects of statins are mediated in part through the inhibition of COX-2 and prostanoids. Rac GTPase protein is identified as one of the targets of statins in this regulation.


Subject(s)
Cyclooxygenase 2/genetics , Gene Expression Regulation/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Membrane Proteins/genetics , Monocytes/metabolism , Humans , Lipopolysaccharides/pharmacology , Lovastatin/analogs & derivatives , Lovastatin/pharmacology , Mevalonic Acid/metabolism , NF-kappa B/metabolism , Simvastatin/pharmacology , U937 Cells , rac GTP-Binding Proteins/drug effects , RAC2 GTP-Binding Protein
18.
Clin Drug Investig ; 38(5): 439-448, 2018 May.
Article in English | MEDLINE | ID: mdl-29417463

ABSTRACT

BACKGROUND AND OBJECTIVES: The purpose of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence and to investigate the pharmacokinetic properties of two formulations of fixed dose combination (FDC) tablet of sofosbuvir (SOF) and ledipasvir (LED) (400/90 mg) in 36 healthy Egyptian volunteers. METHODS: The study was performed in single-dose, randomized-sequence, open-label, reference-replicated, 3-period crossover design (RTR, TRR, RRT), with a washout period of 2 weeks. A rapid and simple LC-MS/MS method was developed and validated for the simultaneous estimation of SOF and LED using eplerenone as an internal standard (IS). RESULTS: The results showed that the 90% confidence intervals (CIs) for natural log-transformed ratios of Cmax, AUClast and AUC∞ of SOF (89.95-115.31, 98.77-109.75 and 98.79-109.75) were within the RSABE acceptance limits. The 90% CIs for natural log-transformed ratios of Cmax and AUClast of LED (87.33-115.15 and 83.82-112.26) were within the FDA bioequivalence limits (80.00-125.00). In addition, the in vitro dissolution study was done and both formulations released > 85% of drug within 15 min in the proposed dissolution medium. CONCLUSIONS: In conclusion, bioequivalence between the two fixed-dose combination products was demonstrated for both active ingredients.


Subject(s)
Benzimidazoles/administration & dosage , Benzimidazoles/pharmacokinetics , Drugs, Generic/administration & dosage , Drugs, Generic/pharmacokinetics , Fluorenes/administration & dosage , Fluorenes/pharmacokinetics , Sofosbuvir/administration & dosage , Sofosbuvir/pharmacokinetics , Adolescent , Adult , Area Under Curve , Chromatography, Liquid , Cross-Over Studies , Drug Compounding , Drug Therapy, Combination , Egypt/epidemiology , Female , Healthy Volunteers , Humans , Male , Middle Aged , Reference Standards , Tablets , Tandem Mass Spectrometry , Therapeutic Equivalency , Young Adult
19.
Ethn Dis ; 17(2): 274-9, 2007.
Article in English | MEDLINE | ID: mdl-17682358

ABSTRACT

OBJECTIVES: In the absence of reliable, contemporary national data, the ACTION survey was designed to: a) provide preliminary data on stroke risk in the MEA (Middle East and Africa); b) describe the contribution of specific cardiovascular risk factors; 3) assess blood pressure (BP) control. DESIGN AND PATIENTS: This was a multi-center observational study in nine countries in the MEA region. From 2003 to 2005, 562 physicians from a variety of specialties recorded observations of cardiovascular risk factors in 4,747 hypertensive patients, aged 54-80 years. The 10-year absolute stroke risk was calculated using a scoring system based on the Framingham Heart Study observations, and comparisons made with an age-matched cohort. RESULTS: The mean 10-year stroke risk was estimated at 22.7% and was significantly higher for men (25.4%) than for women (19.5%) (P < .001) and for diabetics (28.2%) than for non-diabetics (19.4%) (P < .001). Compared with an age-matched Framingham cohort, the estimated stroke risk in our population was almost double, and was significantly higher for females (212%) than for males (192%) (P < .001). Hypertension, diabetes, left ventricular hypertrophy, and smoking were major contributing risk factors, as were physical inactivity and elevated cholesterol. Blood pressure was controlled in only 18% of the population and in 12% of diabetics. CONCLUSION: Physicians of all specialties were willing to participate in stroke risk assessment. The risk of stroke in hypertensive patients in the MEA region is high, and is higher than would be predicted using Framingham data, particularly for females. Hypertension appears to be poorly controlled in more than 80% of hypertensive patients in the MEA region.


Subject(s)
Hypertension/complications , Physicians , Stroke/etiology , Africa/ethnology , Aged , Female , Health Surveys , Humans , Male , Middle Aged , Middle East/ethnology , Risk Assessment , Risk Factors
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