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2.
Am J Physiol Cell Physiol ; 306(9): C794-804, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24553187

RESUMEN

Excess enzyme-mediated protein O-GlcNAcylation is known to occur with diabetes mellitus. A characteristic of diabetic cardiomyopathy is the development of myocardial fibrosis. The role that enhanced protein O-GlcNAcylation plays in modulating the phenotype of cardiac fibroblasts (CF) is unknown. To address this issue, rat CF were cultured in normal glucose (NG; 5 mM glucose) or high-glucose (HG; 25 mM) media for 48 h. Results demonstrate that CF cultured in HG have higher levels (~50%) of overall protein O-GlcNAcylation vs. NG cells. Key regulators of collagen synthesis such as transforming-growth factor-ß1 (TGF-ß1), SMADs 2/3, and SMAD 7 protein levels, including those of arginase I and II, were altered, leading to increases in collagen levels. The nuclear transcription factor Sp1 and arginase II evidence excess O-GlcNAcylation in HG cells. Expression in CF of an adenovirus coding for the enzyme N-acetylglucosaminidase, which removes O-GlcNAc moieties from proteins, decreased Sp1 and arginase II O-GlcNAcylation and restored HG-induced perturbations in CF back to NG levels. These findings may have important pathophysiological implications for the development of diabetes-induced cardiac fibrosis.


Asunto(s)
Colágeno/biosíntesis , Cardiomiopatías Diabéticas/metabolismo , Fibroblastos/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Procesamiento Proteico-Postraduccional , Acetilglucosaminidasa/genética , Acetilglucosaminidasa/metabolismo , Animales , Arginasa/metabolismo , Células Cultivadas , Cardiomiopatías Diabéticas/patología , Fibroblastos/patología , Glicosilación , Masculino , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Transcripción Sp1/metabolismo , Factores de Tiempo , Transfección , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba
3.
Am J Pharm Educ ; 88(9): 101260, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39128793

RESUMEN

OBJECTIVE: To describe the development of an innovative prepharmacy underrepresented mentorship program (PUMP) to provide guidance and support to prepharmacy students who are committed to serving underrepresented communities with health disparities. METHODS: Three virtual PUMP workshops were designed and delivered per admissions cycle for prepharmacy students who were applying to any school of pharmacy and self-identified as interested in serving underrepresented communities. Faculty, current pharmacy students, staff, and school leadership provided guidance and support on the application and interview process and how to select a program once offered admission. Data collection included the number of students who attended each workshop and were accepted to and matriculated at the school of pharmacy. Preworkshop and postworkshop surveys provided insight into communities that attendees were committed to serving, perceptions of the workshops, and intent to matriculate, if accepted. RESULTS: During the first three admissions cycles, 189 prepharmacy students participated in 8 PUMP workshops. A favorable trend was observed with an increased number of participants annually and an increased number of attendees who matriculated (an average of 34% over 3 cycles). Attendees were committed to addressing health disparities in various communities including but not limited to Southeast Asian; Latinx; Native American; lesbian, gay, bisexual, transgender, queer/questioning, intersex, or asexual; Black/African American; Refugee; and Pacific Islanders. Most attendees (96%) reported that attending PUMP workshop(s) positively changed their impression of the school. CONCLUSION: A pilot prepharmacy mentorship program was developed and implemented. A growth in program participation and matriculation of students over 3 cycles who self-identified as committed to serving underrepresented communities was observed.


Asunto(s)
Educación en Farmacia , Mentores , Grupos Minoritarios , Estudiantes de Farmacia , Humanos , Educación en Farmacia/métodos , Masculino , Femenino , Facultades de Farmacia , Desarrollo de Programa , Encuestas y Cuestionarios , Criterios de Admisión Escolar
4.
Public Health Pract (Oxf) ; 7: 100512, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38846106

RESUMEN

Objectives: Research on links between social, geographic, and cultural determinants of health has been thwarted by inadequate measures of culture. The purpose of this study was to improve the measurement of community culture, defined as shared patterns of attitudes and behaviors among people within a neighborhood that distinguish it from others, and to examine dimensions of culture, independent of socioeconomic and demographic factors, and their relationships with health. Study design: A survey research design with correlational analyses was used. Methods: A survey packet including the Community Culture Survey - Revised (CCS-R), demographic, health, and other individual-level measures was administered through convenience sampling across the United States (US) and to a sample in Thailand from 2016 to 2018. US county-level variables were obtained from zip codes. Results: 1930 participants from 49 US states (n = 1592) and Thailand (n = 338) completed all CCS-R items, from which 12 subscales were derived: Social Support & Connectedness, Responsibility for Self & Others, Family Ties & Duties, Social Distress, Urban Diversity, Discontinuity, Church-Engaged, External Resource-Seeking, Locally Owned Business-Active, Power Deference, Next Generation Focus, and Self-Reliance. Neighborhood culture subscale scores varied more by geography than by participant's demographics. All subscales predicted one or more health indicator, and some of these relationships were significant after adjusting for participant age and county-level socioeconomic variables. Most of the significant differences on subscales by race/ethnicity were no longer significant after adjusting for participant's age and county-level socioeconomic variables. Most rural/urban and regional differences in culture within the US persisted after these adjustments. Based on correlational analyses, Social Support & Connectedness and Responsibility for Self & Others were the best predictors of participants' overall health and quality of life, and Responsibility for Self & Others was the best predictor (inversely) of the CDC's measures of social vulnerability. Conclusions: Neighborhood culture is measurable, multi-dimensional, distinct from race/ethnicity, and related to health even after controlling for age and socioeconomic factors. The CCS-R is useful for advancing research and practice addressing the complex interactions between individuals, their neighborhood communities, and health outcomes.

5.
Am J Physiol Cell Physiol ; 304(3): C248-56, 2013 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-23151801

RESUMEN

Sorcin localizes in cellular membranes and has been demonstrated to modulate cytosolic Ca(2+) handling in cardiac myocytes. Sorcin also localizes in mitochondria; however, the effect of sorcin on mitochondrial Ca(2+) handling is unknown. Using mitochondrial pericam, we measured mitochondrial Ca(2+) concentration and fluxes in intact neonatal cardiac myocytes overexpressing sorcin. Our results showed that sorcin increases basal and caffeine-stimulated mitochondrial Ca(2+) concentration. This effect was associated with faster Ca(2+) uptake and release. The effect of sorcin was specific for mitochondria, since similar results were obtained with digitonin-permeabilized cells, where cytosolic Ca(2+) flux was disrupted. Furthermore, mitochondria of cardiac myocytes in which sorcin was overexpressed were more Ca(2+)-tolerant. Experiments analyzing apoptotic signaling demonstrated that sorcin prevented 2-deoxyglucose-induced cytochrome c release. Furthermore, sorcin prevented hyperglycemia-induced cytochrome c release and caspase activation. In contrast, antisense sorcin induced caspase-3 activation. Thus, sorcin antiapoptotic properties may be due to modulation of mitochondrial Ca(2+) handling in cardiac myocytes.


Asunto(s)
Apoptosis/fisiología , Proteínas de Unión al Calcio/metabolismo , Calcio/metabolismo , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Cafeína/farmacología , Caspasa 3/metabolismo , Citocromos c/metabolismo , Mitocondrias/efectos de los fármacos , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Ratas
6.
Cureus ; 15(8): e42970, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37671214

RESUMEN

Cervical cancer is the second most common cancer among women under 50 years of age in Pakistan. The current study was designed to assess the level of awareness through educational outreach presentations about cervical cancer, Papanicolaou (Pap) smear test, and human papillomavirus (HPV) vaccination in Karachi, Pakistan. Women from different urban hospitals were enrolled. Participants participated in a 45-minute presentation on cervical cancer awareness led by student pharmacists from Nazeer Hussain University, Karachi. A pre-and post-test was administered to assess the impact of the intervention. Descriptive statistics were used to summarize the findings, and a t-test was used for matched comparison, and a p-value <0.05 for statistical significance. A total of 150 women participated in the study. The study found that Pakistani women living in urban settings were less knowledgeable about the causes of cervical cancer and prevention. After the presentation, we observed a 45% increase in knowledge, and 31% of participants said they would obtain a Pap smear test in the next six months. Supervised pharmacy student-led presentations on cervical cancer educational awareness that significantly impacted women participants. Pharmacists can play a key role in reducing cervical cancer deaths through increased awareness, education, prevention, and immunization.

7.
Am J Physiol Regul Integr Comp Physiol ; 303(7): R689-99, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-22874425

RESUMEN

We examined the role that enzymatic protein O-GlcNAcylation plays in the development of diabetic cardiomyopathy in a mouse model of Type 2 diabetes mellitus (DM2). Mice injected with low-dose streptozotocin and fed a high-fat diet developed mild hyperglycemia and obesity consistent with DM2. Studies were performed from 1 to 6 mo after initiating the DM2 protocol. After 1 mo, DM2 mice showed increased body weight, impaired fasting blood glucose, and hyperinsulinemia. Echocardiographic evaluation revealed left ventricular diastolic dysfunction by 2 mo and O-GlcNAcylation of several cardiac proteins and of nuclear transcription factor Sp1. By 4 mo, systolic dysfunction was observed and sarcoplasmic reticulum Ca(2+) ATPase expression decreased by 50%. Fibrosis was not observed at any timepoint in DM2 mice. Levels of the rate-limiting enzyme of the hexosamine biosynthetic pathway, glutamine:fructose-6-phosphate amidotransferase (GFAT) were increased as early as 2 mo. Fatty acids, which are elevated in DM2 mice, can possibly be linked to excessive protein O-GlcNAcylation levels, as cultured cardiac myocytes in normal glucose treated with oleic acid showed increased O-GlcNAcylation and GFAT levels. These data indicate that the early onset of diastolic dysfunction followed by the loss of systolic function, in the absence of cardiac hypertrophy or fibrosis, is associated with increased cardiac protein O-GlcNAcylation and increased O-GlcNAcylation levels of key calcium-handling proteins. A link between excessive protein O-GlcNAcylation and cardiac dysfunction is further supported by results showing that reducing O-GlcNAcylation by O-GlcNAcase overexpression improved cardiac function in the diabetic mouse. In addition, fatty acids play a role in stimulating excess O-GlcNAcylation. The nature and time course of changes observed in cardiac function suggest that protein O-GlcNAcylation plays a mechanistic role in the triggering of diabetic cardiomyopathy in DM2.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatías Diabéticas/metabolismo , Progresión de la Enfermedad , Miocitos Cardíacos/metabolismo , Proteínas/metabolismo , Animales , Células Cultivadas , Diabetes Mellitus Experimental/inducido químicamente , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Ecocardiografía , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/metabolismo , Glicosilación , Ratones , Ratones Endogámicos C57BL , N-Acetilglucosaminiltransferasas/metabolismo , Estreptozocina/efectos adversos , Disfunción Ventricular Izquierda , beta-N-Acetilhexosaminidasas/metabolismo
8.
AIMS Public Health ; 9(3): 552-558, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330281

RESUMEN

The objective of this study was to assess the rate of effectiveness of cervical cancer awareness outreach among Vietnamese women in San Diego, USA. In collaboration with different community partners, educational seminars were hosted by student pharmacists in the Vietnamese community. We hypothesized that the seminars would increase cervical cancer awareness and encourage a positive outlook on obtaining annual Pap smears and HPV vaccines. The study design included pre- and post-intervention assessment surveys in either Vietnamese or English language. The surveys were administered to Vietnamese women who participated in the seminars. Eight seminars were hosted at local health fairs in San Diego. A total of 120 Vietnamese women participated in the seminars. Our study showed that educational seminars significantly improved the knowledge about cervical cancer, Pap smears and HPV vaccines. By comparing the pre- and post-intervention surveys, we observed an improvement in knowledge about cervical cancer (61% vs 93%, p < 0.001) and a positive change in the attitude towards obtaining a Pap smear within a year following the educational intervention (57% vs. 78%, p < 0.002). Therefore, we concluded that the educational health outreach seminars presented by student pharmacists are an effective educational model to help improve knowledge about cervical cancer and prevention among Vietnamese women.

9.
Am J Physiol Cell Physiol ; 299(3): C539-48, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20592239

RESUMEN

There must be something unique about a class of drugs (discovered and developed in the mid-1940s) where there are more than 130 ongoing clinical trials currently listed. Tetracyclines were developed as a result of the screening of soil samples for antibiotic organisms. The first of these compounds chlortetracycline was introduced in 1948. Soon after their development tetracyclines were found to be highly effective against various pathogens including rickettsiae, Gram-positive, and Gram-negative bacteria, thus, becoming a class of broad-spectrum antibiotics. The mechanism of action of tetracyclines is thought to be related to the inhibition of protein synthesis by binding to the 30S bacterial ribosome. Tetracyclines are also an effective anti-malarial drug. Over time, many other "protective" actions have been described for tetracyclines. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Its mechanism of action appears to relate to specific effects exerted on apoptosis signaling pathways. Another tetracycline, doxycycline is known to exert antiprotease activities. Doxycycline can inhibit matrix metalloproteinases, which contribute to tissue destruction activities in diseases such as gingivitis. A large body of literature has provided additional evidence for the "beneficial" actions of tetracyclines, including their ability to act as oxygen radical scavengers and anti-inflammatory agents. This increasing volume of published work and ongoing clinical trials supports the notion that a more systematic examination of their possible therapeutic uses is warranted. This review provides a summary of tetracycline's multiple mechanisms of action and while using the effects on the heart as an example, this review also notes their potential to benefit patients suffering from various pathologies such as cancer, Rosacea, and Parkinson's disease.


Asunto(s)
Tetraciclinas/farmacología , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Apoptosis/efectos de los fármacos , Ensayos Clínicos como Asunto , Humanos , Tetraciclinas/química , Tetraciclinas/uso terapéutico
10.
Am J Pharm Educ ; 81(2): 32, 2017 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-28381892

RESUMEN

Objective. To implement and evaluate the effectiveness of an interactive health literacy program by measuring pharmacy students' knowledge and confidence. Design. A health literacy module consisting of a lecture and workshop was incorporated into a self-care course for first-year pharmacy students. Active-learning activities included practicing health literacy tools, discussing faculty-created video vignettes, and improving readability of patient education monographs. A non-validated survey assessed knowledge and confidence before and after training. Assessment. Fifty-three students (88%) completed a pre-training survey, and 60 (100%) completed a post-training survey. Students' confidence improved in six of seven areas (p<.001). Students' knowledge significantly improved in three of 14 areas (p<.01) pertaining to the average American reading level, high-risk age groups, and correlation of late prescription refills to low health literacy. Although knowledge increased in other areas, the improvements were not significant. Conclusion. An interactive, multifaceted health literacy training program significantly improved pharmacy students' knowledge and confidence in recognizing and being able to assist patients with low health literacy.


Asunto(s)
Educación en Farmacia/métodos , Conocimientos, Actitudes y Práctica en Salud , Alfabetización en Salud/métodos , Aprendizaje Basado en Problemas/métodos , Estudiantes de Farmacia , Adolescente , Adulto , Anciano , Evaluación Educacional/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
11.
J Biol Chem ; 284(1): 547-555, 2009 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-19004814

RESUMEN

Increased nuclear protein O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation) mediated by high glucose treatment or the hyperglycemia of diabetes mellitus contributes to cardiac myocyte dysfunction. However, whether mitochondrial proteins in cardiac myocytes are also submitted to O-GlcNAcylation or excessive O-GlcNAcylation alters mitochondrial function is unknown. In this study, we determined if mitochondrial proteins are O-GlcNAcylated and explored if increased O-GlcNAcylation is linked to high glucose-induced mitochondrial dysfunction in neonatal rat cardiomyocytes. By immunoprecipitation, we found that several mitochondrial proteins, which are members of complexes of the respiratory chain, like subunit NDUFA9 of complex I, subunits core 1 and core 2 of complex III, and the mitochondrial DNA-encoded subunit I of complex IV (COX I) are O-GlcNAcylated. By mass spectrometry, we identified that serine 156 on NDUFA9 is O-GlcNAcylated. High glucose treatment (30 mm glucose) increases mitochondrial protein O-GlcNAcylation, including those of COX I and NDUFA9 which are reduced by expression of O-GlcNAcase (GCA). Increased mitochondrial O-GlcNAcylation is associated with impaired activity of complex I, III, and IV in addition to lower mitochondrial calcium and cellular ATP content. When the excessive O-GlcNAc modification is reduced by GCA expression, mitochondrial function improves; the activity of complex I, III, and IV increases to normal and mitochondrial calcium and cellular ATP content are returned to control levels. From these results we conclude that specific mitochondrial proteins of cardiac myocytes are O-GlcNAcylated and that exposure to high glucose increases mitochondrial protein O-GlcNAcylation, which in turn contributes to impaired mitochondrial function.


Asunto(s)
Diabetes Mellitus/enzimología , Glucosa/farmacología , Glucosiltransferasas/biosíntesis , Mitocondrias Cardíacas/enzimología , Proteínas Mitocondriales/biosíntesis , Miocitos Cardíacos/enzimología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Edulcorantes/farmacología , Acetilglucosamina/genética , Acetilglucosamina/metabolismo , Animales , Ciclooxigenasa 1/metabolismo , Diabetes Mellitus/patología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glicosilación/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Ratones , Mitocondrias Cardíacas/patología , Miocitos Cardíacos/patología , NADH Deshidrogenasa/metabolismo , Ratas
12.
J Am Coll Cardiol ; 52(13): 1086-94, 2008 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-18848143

RESUMEN

OBJECTIVES: The ability of minocycline to be transported into cardiac cells, concentrate in normal and ischemic myocardium, and act as a cardioprotector in vivo was examined. We also determined minocycline's capacity to act as a reducer of myocardial oxidative stress and matrix metalloproteinase (MMP) activity. BACKGROUND: The identification of compounds with the potential to reduce myocardial ischemic injury is of great interest. Tetracyclines are antibiotics with pleiotropic cytoprotective properties that accumulate in normal and diseased tissues. Minocycline is highly lipophilic and has shown promise as a possible cardioprotector. However, minocycline's potential as an in vivo cardioprotector as well as the means by which this action is attained are not well understood. METHODS: Rats were subjected to 45 min of ischemia and 48 h of reperfusion. Animals were treated 48 h before and 48 h after thoracotomy with either vehicle or 50 mg/kg/day minocycline. Tissue samples were used for biochemical assays and cultured cardiac cells for minocycline uptake experiments. RESULTS: Minocycline significantly reduced infarct size (approximately 33%), tissue MMP-9 activity, and oxidative stress. Minocycline was concentrated approximately 24-fold in normal (0.5 mmol/l) and approximately 50-fold in ischemic regions (1.1 mmol/l) versus blood. Neonatal rat cardiac fibroblasts, myocytes, and adult fibroblasts demonstrated a time- and temperature-dependent uptake of minocycline to levels that approximate those of normal myocardium. CONCLUSIONS: Given the high intracellular levels observed and results from the assessment of in vitro antioxidant and MMP inhibitor capacities, it is likely that minocycline acts to limit myocardial ischemic injury via mass action effects.


Asunto(s)
Cardiotónicos/uso terapéutico , Minociclina/uso terapéutico , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacocinética , Antioxidantes/uso terapéutico , Cardiotónicos/metabolismo , Cardiotónicos/farmacocinética , Masculino , Inhibidores de la Metaloproteinasa de la Matriz , Minociclina/metabolismo , Minociclina/farmacocinética , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba
13.
Am J Physiol Cell Physiol ; 295(6): C1561-8, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19060297

RESUMEN

Mitochondrial transcription factor A (TFAM) is essential for mitochondrial DNA transcription and replication. TFAM transcriptional activity is decreased in diabetic cardiomyopathy; however, the functional implications are unknown. We hypothesized that a reduced TFAM activity may be responsible for some of the alterations caused by hyperglycemia. Therefore, we investigated the effect of TFAM overexpression on hyperglycemia-induced cytosolic calcium handling and mitochondrial abnormalities. Neonatal rat cardiomyocytes were exposed to high glucose (30 mM) for 48 h, and we examined whether TFAM overexpression, by protecting mitochondrial DNA, could reestablish calcium fluxes and mitochondrial alterations toward normal. Our results shown that TFAM overexpression increased to more than twofold mitochondria copy number in cells treated either with normal (5.5 mM) or high glucose. ATP content was reduced by 30% and mitochondrial calcium decreased by 40% after high glucose. TFAM overexpression returned these parameters to even higher than control values. Calcium transients were prolonged by 70% after high glucose, which was associated with diminished sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a and cytochrome-c oxidase subunit 1 expression. These parameters were returned to control values after TFAM overexpression. High glucose-induced protein oxidation was reduced by TFAM overexpression, indicating a reduction of the high glucose-induced oxidative stress. In addition, we found that TFAM activity can be modulated by O-linked beta-N-acetylglucosamine glycosylation. In conclusion, TFAM overexpression protected cell function against the damage induced by high glucose in cardiomyocytes.


Asunto(s)
Calcio/metabolismo , Citoplasma/metabolismo , Hiperglucemia/fisiopatología , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Factores de Transcripción/metabolismo , Animales , Citoplasma/química , ADN Mitocondrial/genética , Ensayo de Cambio de Movilidad Electroforética , Dosificación de Gen , Glicosilación , Hiperglucemia/metabolismo , Mitocondrias/patología , Miocitos Cardíacos/patología , Reacción en Cadena de la Polimerasa , Ratas , Factores de Transcripción/genética
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