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1.
Mo Med ; 120(2): 143-150, 2023.
Article in English | MEDLINE | ID: mdl-37091940

ABSTRACT

Physician-mentored patient rounds (PMPR) were used to assess diagnostic accuracy and treatment plans of preclinical medical students. During 4 PMPR sessions, students gathered patient history, observed a physical exam, analyzed diagnostic tests, and developed treatment plans for a patient with chronic obstructive pulmonary disease. Of 470 students, 99.4% correctly diagnosed the patient. Nearly 78% prescribed long-acting beta-agonists or long-acting muscarinic antagonists. Most included appropriate pharmacologic treatments. Only 47% included smoking cessation in their treatment.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Smoking Cessation , Students, Medical , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Muscarinic Antagonists/therapeutic use , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use
2.
BMC Med Educ ; 22(1): 218, 2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35354406

ABSTRACT

BACKGROUND: The coronavirus (COVID-19) pandemic required a transformation of medical education in Egypt. Public health measures necessitated a rapid shift from traditional face to face lectures to largely online platforms following campus closures. The aim of this study is to characterize medical student use and perception of online medical education in Egypt as well as exploring the efficacy of different e-learning modalities. Additionally, many barriers and opportunities as perceived by students are reviewed to inform future educational improvements. METHODS: A 29-item online survey was created on google forms and distributed by social media to medical students across 26 Egyptian medical schools. The survey was administered from August 20th, 2021, to September 5th, 2021. The survey consisted of a mixture of questions style. The medical students were asked about their experiences with online medical education during the COVID-19 pandemic as well as medical students' anxiety, perceived academic performance, and obstacles related to online education. RESULTS: Of the 4935 responses collected, 43.4% (n = 2140) of respondents were women; 56.6% (n = 2795) were men. Medical students from private medical schools were 13.0% (n = 644), whereas 87.0% (n = 4291) were from public medical schools. 54.6% of students reported that online education is not as effective as face-to-face education. There was a significant rise in hours spent by medical students on online medical education compared to before COVID-19 pandemic. More than half of students (63%) agreed that online recorded video tutorials (e.g., YouTube) were the most effective form of online medical education. CONCLUSION: The shift to online education has significantly impacted medical students in Egypt. Medical students reported various limitations and challenges of online medical education, which must be addressed considering the potential benefits of online platforms over traditional face to face learning. The results of this nationwide study provide a framework for potential areas to implement change to improve the accessibility and structure of online medical education in Egypt.


Subject(s)
COVID-19 , Education, Distance , Education, Medical , Students, Medical , COVID-19/epidemiology , Education, Distance/methods , Egypt/epidemiology , Female , Humans , Male , Pandemics , Schools, Medical
3.
J Am Osteopath Assoc ; 120(11): 749-760, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-32946547

ABSTRACT

CONTEXT: Competency-based medical education, developmental milestones for residency training, and the single graduate medical education (GME) accreditation system have emerged over the last decade, necessitating new ways to adequately prepare graduates to meet new standards in proficiency, including the 13 Core Entrustable Professional Activities (EPA) for Entering Residency. The American Association of Colleges of Osteopathic Medicine (AACOM) Entrustable Professional Activities (EPA) steering committee has implemented an information-gathering process to provide suggestions for supporting a variety of EPA-related implementation efforts at colleges of osteopathic medicine (COMs) across the country. OBJECTIVE: To review the status of EPA implementation at COMs nationally. METHODS: An explanatory mixed-methods design was used to guide information gathering and synthesis of a 41-question survey and interview feedback; the overarching premise of this design was to use qualitative data to build upon initial quantitative findings. This survey was delivered electronically through a link emailed to liaisons at each main, branch, and satellite campus of the 47 schools within the AACOM institutional database. After survey administration, follow-up structured interviews were conducted according to an 18-question script with a purposive sample of 16 institutions with EPA implementation levels ranging from "moderate implementation with reporting" to "full implementation with reporting." Post-interview, the interview notes were analyzed and results were aggregated for comparison with the original survey findings. RESULTS: Of the 47 schools surveyed, 42 responded (89.4%). To maintain uniformity in data coding and analysis, 36 of 47 (76.6%) of COMs with independently submitted survey responses were retained in the review. The majority of those respondents (23 of 36; 64%) indicated that their institution was above "somewhat knowledgeable" toward "expert" regarding knowledge of EPAs, but 23 (64%) also indicated "no confidence" or "somewhat confident" regarding EPA implementation. Postinterview results showed that the majority of schools were equally distributed across the "foundational implementation" (10; 28%), "slight implementation" (11; 31%), and "moderate implementation" (11, 31%) categories, with a few schools indicating "no implementation" (2; 5%) or "progressive implementation" (2; 5%). CONCLUSION: The results of this review indicate that most osteopathic medical schools are at the early stages of EPA implementation, with emphasis varying by program year in terms of the specific EPAs addressed. Many schools appear engaged in curricular change efforts that will support the advancement of EPA use within their institutions. Faculty development was identified as a continued critical need for a majority of institutions.


Subject(s)
Internship and Residency , Osteopathic Medicine , Clinical Competence , Competency-Based Education , Education, Medical, Graduate , Humans , Osteopathic Medicine/education , United States
4.
Mo Med ; 115(1): 35-36, 2018.
Article in English | MEDLINE | ID: mdl-30228680

ABSTRACT

The amount of scientific and medical information students are expected to master is ever increasing. This may draw attention away from the human aspect of medicine - the reason most enter medical school in the first place. Medical humanities may help students remain empathetic, self-aware and reflective as they work to become excellent physicians.


Subject(s)
Curriculum , Education, Medical/methods , Humanities/education , Students, Medical/psychology , Adult , Empathy , Female , Humans , Male , Osteopathic Medicine/education , Schools, Medical
5.
J Am Osteopath Assoc ; 118(3): 199-206, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29480920

ABSTRACT

CONTEXT: Thirteen entrustable professional activities (EPAs) for entering residency were created to aid medical educators as they prepare preclinical students for their residency and to assess student readiness for residency. The A.T. Still University Kirksville College of Osteopathic Medicine (ATSU-KCOM) developed a program called physician-mentored patient rounds (PMPR), which focuses on EPA 1 and EPA 2. OBJECTIVE: To determine whether PMPRs could be used to assess expected behaviors of EPA 1 (gather a history and perform a physical examination) and EPA 2 (prioritize a differential diagnosis after a clinical encounter). METHODS: The PMPR sessions at ATSU-KCOM take place over several weeks (30-minute sessions per week), during which students gather a patient's history (sessions 1 and 2), observe a physical examination by the physician mentor (session 2), analyze diagnostic test results (session 3), and formulate a treatment plan (session 4). The PMPRs in this study used a real patient with confirmed chronic obstructive pulmonary disease (COPD). This study did not include the session-4 treatment plan. Between sessions, students completed an assignment to further demonstrate their behaviors as expected in the EPAs. Student responses were analyzed and summarized for physician feedback in the subsequent PMPR session. Students' diagnostic accuracy was measured at the conclusion of each session. RESULTS: A total of 516 students were included in the study. The PMPR weekly attendance was high (453-475). Although history gathering in the large-group setting was disorderly, diagnostic accuracy over the 3-session period improved. After history taking, 411 students (86.5%) included COPD in the differential diagnosis. A smaller number, 235 students (49.5%), listed COPD as the most likely diagnosis. After the physical examination, 439 included COPD in the differential diagnosis, and 385 listed COPD as the most likely diagnosis. After analysis of diagnostic test results, 468 students listed COPD as the most likely diagnosis. CONCLUSION: Physician-mentored patient rounds seem to be an effective means to assess preclinical students' expected behaviors as described in EPA 1 and EPA 2.


Subject(s)
Clinical Competence , Internship and Residency , Mentors , Osteopathic Medicine/education , Teaching Rounds , Diagnosis, Differential , Diagnostic Tests, Routine , Humans , Medical History Taking , Physical Examination , Physician-Patient Relations , Pulmonary Disease, Chronic Obstructive/diagnosis
6.
J Am Osteopath Assoc ; 117(11): 712-718, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29084324

ABSTRACT

Entrustable professional activities (EPAs) are measurable units of observable professional practice that can be entrusted to an unsupervised trainee. They were first introduced as a method of operationalizing competency-based medical education in graduate medical education. The American Association of Medical Colleges subsequently used EPAs to establish the core skills that medical students must be able to perform before they enter residency training. A recently published guide provides descriptions, guidelines, and rationale for implementing and assessing the core EPAs from an osteopathic approach. These osteopathically informed EPAs can allow schools to more appropriately assess a learner's whole-person approach to a patient, in alignment with the philosophy of the profession. As the single accreditation system for graduate medical education moves forward, it will be critical to integrate EPAs into osteopathic medical education to demonstrate entrustment of medical school graduates. The authors describe the collaborative process used to establish the osteopathic considerations added to EPAs and explores the challenges and opportunities for undergraduate osteopathic medical education.


Subject(s)
Clinical Competence/standards , Education, Medical, Undergraduate/standards , Educational Measurement/methods , Osteopathic Medicine/education , Competency-Based Education , Internship and Residency , Osteopathic Medicine/standards , United States
7.
Acad Psychiatry ; 40(1): 55-62, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26108394

ABSTRACT

OBJECTIVE: The purposes of the current study are to examine factors modifying burnout and identify which of these factors place osteopathic medical students at risk for developing burnout. METHODS: The current study used a cross-sectional study design and an anonymous, web-based survey to assess burnout and depression in osteopathic medical students. The survey included Maslach Burnout Inventory, the Patient Health Questionnaire, the Stressors and their impact scale, students' sleeping and studying habits, and students' extracurricular involvement. RESULTS: In total, 1294 osteopathic medical students completed the survey. Burnout was present in 516 (39.9%) osteopathic medical students, and 1006 (77.0%) met criteria for depression. Females were 1.5 times more likely to be burned out in comparison to males. For the burnout subscales, males had lower emotional exhaustion, slightly higher depersonalization, and lower personal accomplishment. Lesbian/gay/bisexual/asexual students were 2.62 times more likely to be burned out compared with heterosexual students. Depression and academic, personal, and family stressors were all strongly linked to overall burnout. Finally, for modifiable factors, average hours of sleep, average hours spent studying, and club involvement appeared to be linked to burnout. CONCLUSIONS: The current study suggested that a variety of factors, including non-modifiable, situational, and modifiable, impact burnout in osteopathic medical students. Future research is necessary since burnout in physicians affects the quality of care provided to patients.


Subject(s)
Burnout, Professional/epidemiology , Osteopathic Medicine/education , Students, Medical/psychology , Adolescent , Adult , Anxiety Disorders/epidemiology , Burnout, Professional/psychology , Cross-Sectional Studies , Depression/epidemiology , Education, Medical, Undergraduate , Female , Humans , Internet , Job Satisfaction , Male , Middle Aged , Sex Factors , Stress, Psychological , Surveys and Questionnaires , United States , Young Adult
8.
Am Ann Deaf ; 160(1): 36-47, 2015.
Article in English | MEDLINE | ID: mdl-26004974

ABSTRACT

The study examined the effectiveness of a workshop on Deaf culture and basic medical American Sign Language for increasing osteopathic student physicians' confidence and knowledge when interacting with ASL-using patients. Students completed a pretest in which they provided basic demographic information, rated their confidence levels, took a video quiz on basic medical signs, and experienced a practical standardized encounter with a Deaf patient. They then attended a 4-hour workshop and, 2 weeks later, completed a posttest. Thirty-three students completed the pretest; 29 attended the workshop; 26 completed the posttest. Video quiz scores increased significantly from pretest to posttest, as did scores for the standardized patient encounter after completion of the workshop. Students also reported increased levels of confidence in interactions with the Deaf community. The results suggest that a single workshop was effective in increasing both confidence and short-term knowledge in interactions with Deaf patients.


Subject(s)
Cultural Competency , Deafness/psychology , Education, Medical, Undergraduate , Osteopathic Medicine/education , Sign Language , Students, Medical/psychology , Teaching/methods , Adolescent , Adult , Attitude of Health Personnel , Clinical Competence , Communication , Cross-Sectional Studies , Educational Measurement , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Physician-Patient Relations , Surveys and Questionnaires , Young Adult
9.
J Am Osteopath Assoc ; 114(10): 788-96, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25288714

ABSTRACT

CONTEXT: Limited research exists on the health issues faced by lesbian, gay, bisexual, and transgender (LGBT) patients, as viewed in the context of osteopathic medical education. A full understanding of current medical students' acceptance of, attitudes toward, and knowledge of these issues could lead to the development and incorporation of curricula focusing on the care of LGBT patients into colleges of osteopathic medicine (COMs). OBJECTIVE: To determine among osteopathic medical students the levels of acceptance of LGBT patients, attitudes toward treating this population, and medically relevant knowledge about their distinct health-related issues. METHODS: In August 2012, students at 6 COMs were sent an e-mail invitation that contained basic information about the study and a link providing access to an anonymous Web-based survey. Standard scales used in previous studies were compiled and individualized into 130 items for the purposes of the present study. RESULTS: Of the 4112 osteopathic medical students contacted, 1698 (41.3%) entered the survey and 1335 (32.5%) completed it. Two hundred respondents (15%) self-identified as having a sexual orientation on the lesbian, gay, or bisexual (LGB) spectrum. Although respondents generally had favorable levels of acceptance of LGBT patients and positive attitudes toward treatment of this population, self-identified LGB students had even greater acceptance of LGBT patients (P<.001) and more positive attitudes toward their treatment (P<.001). When medically relevant knowledge of issues related to the health of LGBT patients was assessed, 125 respondents (12.9%) obtained a passing score of 7 or higher, with LGB students scoring significantly higher than students whose self-identified sexual orientation was heterosexual only (P=.01). Differences in the levels of acceptance of (P=.008), treatment attitudes toward (P=.001), and relevant medical knowledge (P=.05) pertaining to LGBT patients were noted between respondents from the 6 COMs. CONCLUSION: The results suggest that even though osteopathic medical students had mostly positive personal attitudes and treatment attitudes toward LGBT patients, some disparities were still present. Also, students lacked adequate knowledge of the unique medical issues faced by the LGBT population. In the future, students should be given more training to effectively treat LGBT patients and their health-related issues.


Subject(s)
Attitude of Health Personnel , Sexuality , Students, Medical , Transgender Persons , Adolescent , Adult , Female , Humans , Male , Middle Aged , Osteopathic Medicine/education , Surveys and Questionnaires , Young Adult
10.
BMC Med Educ ; 14: 171, 2014 Aug 15.
Article in English | MEDLINE | ID: mdl-25128252

ABSTRACT

BACKGROUND: To investigate the relationship between sexual orientation and gender identity in regard to levels of depression; levels of perceived social support; comfort with disclosure of orientation; and the lesbian, gay, bisexual, and transgender (LGBT) campus climate. METHODS: E-mail invitations to participate in the current cross-sectional questionnaire-based study were sent to all thirty US osteopathic medical schools in August 2012; six schools responded and disseminated the survey to their students. Participating students completed an anonymous web-based survey, and informed consent was obtained when they accessed the survey. The survey was designed specifically for the current study but contained scales used with permission from previously published research. Analysis procedures included nonparametric tests, one-way analysis of variance and Pearson's correlations. RESULTS: Of the 4112 students invited to participate in the survey, 1334 (32.4%) completed it. Approximately 85% of respondents self-identified as heterosexual only. No respondents identified as transgender. In general, LGB students indicated higher levels of depression (P < .001), slightly lower levels of perceived social support (P < .001), and more discomfort with disclosure of sexual orientation (P < .001). A majority of students rated their campus climate as noninclusive. CONCLUSIONS: Results of the current study indicated a relationship between sexual orientation and depression, perceived social support, comfort with disclosure of orientation, and the LGBT campus climate in osteopathic medical students. In the future, osteopathic medical schools should consider closely examining their campus culture in order to create a more positive and inclusive environment for all its students.


Subject(s)
Sexual Behavior/statistics & numerical data , Students, Medical/statistics & numerical data , Adolescent , Adult , Bisexuality/psychology , Bisexuality/statistics & numerical data , Cross-Sectional Studies , Depression/epidemiology , Education, Medical/statistics & numerical data , Female , Homosexuality, Female/psychology , Homosexuality, Female/statistics & numerical data , Homosexuality, Male/psychology , Homosexuality, Male/statistics & numerical data , Humans , Male , Middle Aged , Schools, Medical/statistics & numerical data , Sexual Behavior/psychology , Social Support , Students, Medical/psychology , Surveys and Questionnaires , Transgender Persons/psychology , Transgender Persons/statistics & numerical data , United States/epidemiology , Workforce , Young Adult
11.
Exp Eye Res ; 85(4): 473-81, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17669400

ABSTRACT

Recent studies of the distribution and relative concentration of caveolin-1 in fractions of bovine lens epithelial and fiber cells have led to the novel concept that caveolin-1 may largely exist as a peripheral membrane protein in some cells. Caveolin-1 is typically viewed as a scaffolding protein for caveolae in plasma membrane. In this study, membrane from cultured bovine lens epithelial cells and bovine lens fiber cells were divided into urea soluble and insoluble fractions. Cytosolic lipid vesicles were also recovered from the lens epithelial cells. Lipid-raft domains were recovered from fiber cells following treatment with detergents and examined for caveolin and lipid content. Aliquots of all fractions were Western blotted for caveolin-1. Fluorescence microscopy and double immunofluorescence labeling were used to examine the distribution of caveolin-1 in cultured epithelial cells. Electron micrographs revealed an abundance of caveolae in plasma membrane of cultured lens epithelial cells. About 60% of the caveolin-1 in the epithelial-crude membrane was soluble in urea, a characteristic of peripheral membrane proteins. About 30% of the total was urea-insoluble membrane protein that likely supports the structure of caveolae. The remaining caveolin was part of cytosolic lipid vesicles. By contrast, most caveolin in the bovine lens fiber cell membrane was identified as intrinsic protein, being present at relatively low concentrations in caveolae-free lipid raft domains enriched in cholesterol and sphingomyelin. We estimate that these domains occupied 25-30% of the fiber cell membrane surface. Thus, the status of caveolin-1 in lens epithelial cells appears markedly different from that in fiber cells.


Subject(s)
Caveolin 1/analysis , Eye Proteins/analysis , Lens, Crystalline/chemistry , Animals , Cattle , Cell Fractionation/methods , Cell Membrane/chemistry , Cells, Cultured , Cytoplasmic Vesicles/chemistry , Epithelial Cells/chemistry , Fluorescent Antibody Technique/methods , Lens Capsule, Crystalline/chemistry , Lens Cortex, Crystalline/chemistry , Membrane Microdomains/chemistry , Sphingomyelins/analysis
12.
Exp Eye Res ; 82(2): 229-35, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16125174

ABSTRACT

Two-dimensional immunoblots of immunoprecipitated caveolin-1 from cultured bovine lens epithelial cells revealed four to five-22 kDa forms of caveolin-1 alpha with isoelectric points of between pH values 5.5 and 6.6. Fibre cell membrane recovered from fresh bovine lenses displayed an even greater number of multiforms, some with isoelectric point pH values as low as about 4. Caveolin-1 can be both phosphorylated and palmitoylated. None of the caveolin-1 alpha multiforms were labelled following culture of the lens epithelial cells with 32P-orthophosphate nor were they recognized by either caveolin-specific phosphotyrosine antibody or protein anti-phosphoserine antibody and treatment of lens fibre cell membrane with phosphatase did not alter the two-dimensional profile of immunoreactive caveolins. However, short-term incubation of BLEC with 3H-palmitate labelled some of the immunoprecipitated caveolin-1 multiforms. We suggest that the observed spectrum of caveolin multiforms could reflect variable palmitoylation of its three cysteine residues and result in populations of caveolin-1 alpha molecules with separate physical and functional properties.


Subject(s)
Caveolin 1/analysis , Epithelial Cells/chemistry , Lens, Crystalline/cytology , Animals , Blotting, Western/methods , Cattle , Caveolin 1/metabolism , Cell Membrane/chemistry , Cell Membrane/metabolism , Cells, Cultured , Epithelial Cells/metabolism , Hydrogen-Ion Concentration , Immunoprecipitation , Isoelectric Point , Isotope Labeling , Lens, Crystalline/metabolism , Palmitates/metabolism , Protein Isoforms/analysis
13.
Lipids ; 40(6): 635-40, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16149744

ABSTRACT

Treatment of animals or cells with the amphipathic tertiary amine U18666A {3beta-[2-(diethylamino) ethoxy]androst-5-en-17-one} provides models for several human diseases (e.g., cataracts, Niemann-Pick disease, and epilepsy). Although U18666A can inhibit several enzymes in the cholesterol synthesis pathway, we hypothesized that induction of these varied conditions was due to physical effects of the amine rather than to inhibition of specific proteins. To test this possibility we compared the capacity of U18666A and its enantiomer, ent-U18666A, to inhibit net sterol synthesis and induce apoptosis in cultured bovine lens epithelial cells. Nonenantiospecific actions dependent on the physical properties of these mirror image molecules would be identical, but effects dependent upon enantiospecific interactions would be different for the enantiomers. At the same concentrations, both forms of the compound equally inhibited sterol synthesis and induced apoptosis. These observations supported a generalized mechanism of enzyme inhibition such as perturbation of the microenvironment of endoplasmic enzymes and alteration of membrane order, perhaps of the mitochondrial membrane, to explain induction of apoptosis.


Subject(s)
Androstenes/chemistry , Androstenes/pharmacology , Apoptosis/drug effects , Sterols/biosynthesis , Animals , Cattle , Cells, Cultured , Lens, Crystalline/drug effects , Lens, Crystalline/metabolism , Lens, Crystalline/pathology , Stereoisomerism
14.
Mol Vis ; 11: 594-602, 2005 Aug 10.
Article in English | MEDLINE | ID: mdl-16110301

ABSTRACT

PURPOSE: Ubiquinone (Ub) is the only known endogenously synthesized lipid soluble antioxidant. It is synthesized from intermediates in the cholesterol metabolic pathway. Our goal was to identify the Ubs and determine the concentration and distribution of Ubs in the rat lens and the effect of treatment with simvastatin, a cholesterol synthesis inhibitor, on lens levels. METHODS: Intact lenses and separated lens fractions from young rats were homogenized in organic solvents, the Ubs recovered, and identified by HPLC analysis. Rats were fed Ub-10 to determine effects of supplementation on tissue levels. Sprague-Dawley (SD) and Chbb:Thom (CT) rats were treated with simvastatin, an inducer of cataracts in CT rats, to determine its effects on lens Ubs. RESULTS: Ubiquinone-9 (9 isoprenes in its hydrocarbon tail) was the main Ub in the rat lens. The intact lens contained about 3.0 microg Ub/g lens wet weight of which 80-90% was Ub-9 and the remainder Ub-10. No reduced Ubs were detected. Although the epithelial fraction contained the highest Ub concentration (about 8 microg/g), the cortex and nucleus combined accounted for about 90% of the lens' total content. Dietary supplementation with Ub-10 markedly increased the Ub-10 concentration in liver but not lens. Treatment with simvastatin decreased lens Ubs of both SD and CT rats by about 20%. CONCLUSIONS: The abundance of mitochondria in lens epithelium likely accounted for its high level of Ubs; but, finding most of the lens' total Ub in the cortex plus nucleus also suggests roles in maintaining the fiber cell membrane. The decrease in lens Ubs caused by simvastatin is interpreted to reflect a response to drug induced cellular stress rather than to inhibition of the cholesterol synthesis pathway.


Subject(s)
Antioxidants/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lens, Crystalline/drug effects , Lens, Crystalline/metabolism , Simvastatin/pharmacology , Ubiquinone/metabolism , Adolescent , Aged , Animals , Cattle , Chromatography, High Pressure Liquid , Humans , Mice , Middle Aged , Oxidation-Reduction , Rats , Rats, Mutant Strains , Rats, Sprague-Dawley
15.
J Lipid Res ; 45(7): 1232-41, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15102886

ABSTRACT

Induction of cataracts in experimental animals is a common toxic feature of oxidosqualene cyclase (OSC) inhibitors. U18666A has been shown to produce irreversible lens damage within a few weeks of treatment. Drug actions, besides reducing the availability of cholesterol, could contribute to cataract formation. Cholesterol added to cultures of lens epithelial cells could only partially overcome the growth-inhibiting effects of U18666A. In view of this finding and the fact that U18666A and other OSC inhibitors are highly lipophilic cationic tertiary amines, we tested the hypothesis that the cataractogenic effect of U18666A is related to direct perturbation of lens membrane structure and function. Based on changes in the anisotropy of fluorescent probes, U18666A incorporated into bovine lens lipid model membranes increased membrane structural order and, using small-angle x-ray diffraction, U18666A was shown to intercalate into the lens lipid model membranes and produce a broad condensing effect on membrane structure. Also, exposure of cultured lens epithelial cells and intact rat lenses to U18666A induced apoptosis. Induction of apoptosis may begin by intercalation of U18666A into cell membranes. By increasing membrane structural order, U18666A may also increase light scatter, thus directly contributing to lens opacification.


Subject(s)
Androstenes/pharmacology , Cataract/chemically induced , Intramolecular Transferases/antagonists & inhibitors , Lens, Crystalline/pathology , Membrane Lipids , Animals , Apoptosis/drug effects , Cataract/etiology , Cattle , Cells, Cultured , Enzyme Inhibitors/pharmacology , Epithelium/pathology , Lens, Crystalline/chemistry , Lens, Crystalline/drug effects , Mice , Phase Transition , Rats , Rats, Sprague-Dawley
16.
Exp Eye Res ; 78(1): 75-82, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14667829

ABSTRACT

The distribution of caveolin-1 in the lens and lens epithelial cells was determined to assess possible roles in cholesterol trafficking, cell to cell communication and signal transduction. Bovine lenses and cultured bovine lens epithelial cells (BLEC) were divided into subcellular fractions and the distribution of proteins recognized by three different caveolin-1 antibodies determined. The immunolocalization of caveolin-1 in the lens epithelium and in subconfluent and confluent cultured BLEC was probed by fluorescence microscopy and laser scanning confocal microscopy. EGF induced phosphorylation of caveolin-1 was detected by Western blotting with an anti-phosphotyrosine antibody to immunoprecipitated caveolin-1 from BLEC and human cancer cells. Monomeric caveolin-1 of about 26 kDa was detected in the epithelial cell membrane of cultured BLEC and fresh epithelia and in the plasma membrane fraction of lens cortical fiber cells. Caveolin-1 of cultured BLEC redistributed from the cytoplasm to plasma membrane as the cells proceeded from subconfluent to confluent states. The apparent abundance of caveolin-1 in cortical fiber cell plasma membrane is consistent with possible roles in distribution of lens membrane cholesterol and membrane structure. The presence of caveolin-1 in the plasma membrane of epithelial cells at - but not before - confluency is consistent with a role of caveolin-1 in cell to cell communications. EGF stimulated phosphorylation of caveolin-1 in human A431 cells but not lens cells.


Subject(s)
Caveolins/analysis , Crystallins/analysis , Lens, Crystalline/chemistry , Animals , Cattle , Caveolin 1 , Caveolins/metabolism , Cell Communication/physiology , Cell Fractionation/methods , Cells, Cultured , Crystallins/metabolism , Epidermal Growth Factor/pharmacology , Epithelial Cells/metabolism , Lens, Crystalline/cytology , Lens, Crystalline/metabolism , Microscopy, Confocal , Microscopy, Fluorescence , Phosphorylation/drug effects
17.
J Lipid Res ; 44(1): 198-211, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12518039

ABSTRACT

Simvastatin rapidly induced cataracts in young Chbb:Thom (CT) but not Sprague Dawley (SD) or Hilltop Wistar (HW) rats. Oral treatment for 14 but not 7 days committed CT rat lenses to cataract formation. The cholesterol to phospholipid molar ratio in lenses of treated CT rats was unchanged. Differences between strains in serum and ocular humor levels of simvastatin acid poorly correlated with susceptibility to cataracts. No significant differences were found between rat strains in the capacity of simvastatin acid to inhibit lens-basal sterol synthesis. Prolonged treatment with simvastatin comparably elevated HMG-CoA reductase protein and enzyme activity in lenses of both cataract resistant and sensitive strains. However, in contrast to SD and HW rats, where sterol synthesis was markedly increased, sterol synthesis in CT rat lenses remained at baseline. Discordant expression of sterol synthesis in CT rats may be due to inadequate upregulation of lens HMG-CoA synthase. HMG-CoA synthase protein levels, and to a much lesser extent mRNA levels, increased in lens cortex of SD but not CT rats. Because upregulation of the sterol pathway may result in increased formation of isoprene-derived anti-inflammatory substances, failure to upregulate the pathway in CT rat lenses may reflect an attenuated compensatory response to injury that resulted in cataracts.


Subject(s)
Cataract/chemically induced , Cataract/metabolism , Lens, Crystalline/drug effects , Lens, Crystalline/metabolism , Simvastatin/analogs & derivatives , Simvastatin/pharmacology , Sterols/metabolism , Animals , Apoptosis , Gene Expression , Hydroxymethylglutaryl CoA Reductases/metabolism , Kinetics , Organ Size , Rats , Rats, Inbred Strains , Simvastatin/analysis , Simvastatin/blood , Sterols/biosynthesis
18.
Biochem Biophys Res Commun ; 295(4): 1027-31, 2002 Jul 26.
Article in English | MEDLINE | ID: mdl-12127999

ABSTRACT

This study describes the use of magnetic Dynabeads to purify microsomes from a crude microsomal fraction. A 28 kDa membrane-associated protein is proposed to mediate the binding of progesterone and other steroid hormones to ocular lens membranes and the rapid-nongenomic actions of these steroids. The subcellular location of this membrane steroid binding protein (MSBP) was probed by capture of organelles containing MSBP by magnetic beads displaying an antibody to a cytoplasmic domain of the protein. The beads were exposed to a crude microsomal fraction from lens epithelia. Western blotting was used to identify captured organelles and confirm the presence of MSBP. Microsomes and trace fiber cell plasma membrane were captured. Microsomes contained the 28 kDa MSBP. Lens fiber cell membrane contained a 55 kDa immunoreactive protein. The role of this serendipitously recognized protein in binding of steroids is unknown.


Subject(s)
Immunomagnetic Separation/methods , Lens, Crystalline/cytology , Membrane Proteins/isolation & purification , Microsomes/metabolism , Animals , Blotting, Western , Cattle , Kinetics , Lens, Crystalline/metabolism , Protein Structure, Tertiary
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