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1.
Int Neurourol J ; 28(1): 4-10, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38569615

RESUMEN

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are particularly prevalent in women. Recurrent UTIs significantly diminish quality of life due to their symptoms and frequent relapses. Patients often experience immediate relapse following slightly strenuous activities or intense psychological stress. In this review, we explore why infections persist despite the advent of various treatments and suggest strategies to manage recurrent cystitis by targeting the mechanisms of adhesion and infection. Vitamin D levels and the expression of neutrophil gelatinase-associated lipocalin are linked to the recurrence of UTIs. During a UTI, bacteria employ adhesins to invade the urinary tract, adhere to urothelial cells, and then penetrate these cells, where they rapidly multiply to establish intracellular bacterial communities. Bacteria can also form quiescent intracellular reservoirs that escape immune responses and antibiotic treatments, leading to recurrence under certain conditions. The surface proteins of bacteria and D-mannose are crucial in the adhesion of bacteria to the urothelium. Understanding these processes provides valuable insights into potential therapeutic approaches that focus on preventing bacterial attachment and cluster formation. By disrupting the ability of bacteria to adhere to and form clusters on cells, we can better manage recurrent UTIs and improve patient outcomes.

2.
Clin Nutr Res ; 12(1): 1-6, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36793777

RESUMEN

Gastrectomy is the most effective method of treating gastric cancer, but it is commonly associated with weight loss, nutritional deficiencies, and the increased risk of malnutrition due to post-surgery complications, including gastric stasis, dumping syndrome, malabsorption, and maldigestion. Malnutrition is a risk factor for postoperative complications and poor prognosis. To prevent it and guarantee a quick recovery after surgery, continuous and individualized nutrition intervention should be performed both before surgery and postoperatively. The Department of Dietetics at Samsung Medical Center (SMC) performed nutritional status assessment before gastrectomy, initial nutritional assessment within 24 hours of admission, description of therapeutic diet after surgery, nutrition counselling before discharge, and nutritional status assessment and individual nutrition counselling after 1, 3, 6, and 12 months from surgery. This is a case report of a patient who underwent gastrectomy as well as intensive nutrition intervention in SMC.

3.
BMC Gastroenterol ; 22(1): 468, 2022 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-36396994

RESUMEN

BACKGROUND: The timing of nutritional assessment may be important to treat cancer patients and predict their prognosis. This study examined whether Patient-Generated Subjective Global Assessment (PG-SGA) and NUTRISCORE scores were associated with survival among gastric cancer patients who underwent surgery and chemotherapy and whether the timing of the assessment after surgery mattered. METHODS: A total of 952 gastric cancer patients (622 men and 330 women) were included in this retrospective cohort study. The PG-SGA and NUTRISCORE scores were calculated at 1 month (n = 952), 2 months (n = 657), and 3 months (n = 294) after surgery. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The PG-SGA scores assessed at 1 month after gastrectomy were not associated with survival. However, high PG-SGA scores at 2 months after gastrectomy (median = 65 days) were associated with an increased risk of mortality; the HR (95% CI) was 2.26 (1.22-4.21) for 9-11 vs. ≤ 5 of PG-SGA scores. When we included patients who received all three consecutive consultations, HR (95% CI) was 2.56 (1.02-6.42) for ≥ 9 (malnutrition) vs. ≤ 8 of PG-SGA scores assessed at 3 months after surgery (median days = 98 days). Likewise, high NUTRISCORE scores assessed at the 3-month follow-up were associated with higher mortality; the HR (95% CI) was 3.84 (1.18-12.55) for ≥ 7 vs. ≤ 4 of NUTRISCORE scores. CONCLUSION: Malnutrition assessed with the PG-SGA and NUTRISCORE at 2 to 3 months after gastrectomy was associated with poor survival among gastric cancer patients. Our findings suggest that the timing of the nutritional evaluation may be important in identifying and treating malnutrition related to gastric cancer prognosis.


Asunto(s)
Desnutrición , Neoplasias Gástricas , Masculino , Humanos , Femenino , Estado Nutricional , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Estudios Retrospectivos , Evaluación Nutricional , Desnutrición/etiología , Desnutrición/complicaciones
4.
Life (Basel) ; 12(3)2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35330146

RESUMEN

Bladder cancer is the fourth most common cancer in men, and most cases are non-muscle-invasive. A high recurrence rate is a critical problem in non-muscle-invasive bladder cancer. The availability of few urine tests hinders the effective detection of superficial and small bladder tumors. Cystoscopy is the gold standard for diagnosis; however, it is associated with urinary tract infections, hematuria, and pain. Early detection is imperative, as intervention influences recurrence. Therefore, urinary biomarkers need to be developed to detect these bladder cancers. Recently, several protein candidates in the urine have been identified as biomarkers. In the present narrative review, the current status of the development of urinary protein biomarkers, including FDA-approved biomarkers, is summarized. Additionally, contemporary proteomic technologies, such as antibody-based methods, mass-spectrometry-based methods, and machine-learning-based diagnosis, are reported. Furthermore, new strategies for the rapid and correct profiling of potential biomarkers of bladder cancer in urine are introduced, along with their limitations. The advantages of urinary protein biomarkers and the development of several related technologies are highlighted in this review. Moreover, an in-depth understanding of the scientific background and available protocols in research and clinical applications of the surveillance of non-muscle bladder cancer is provided.

5.
PLoS One ; 16(5): e0252168, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34019591

RESUMEN

Dietary education is regarded as an important and useful tool for influencing nutritional status. Since long, dietary education has been performed to improve the nutritional status of patients after a gastrectomy. This study aimed to investigate the effect of simplified dietary education on the nutritional status of patients after a gastrectomy. A total of 1,150 patients with gastric cancer underwent surgery between March 2014 and October 2015 at the Samsung Medical Center (SMC). Of these, we used the case-control matching method (1:1 match) by stratifying the factors of age and sex and included 100 patients in each group. The clinicopathologic data of the patients for two years after the gastrectomy were prospectively collected and retrospectively analyzed. The educated group (ED, N = 100) was provided with a simplified, ordinary dietary education at regular outpatient clinic visits that occurred at 1, 3, 6, and 12 months after gastrectomy and at 1-year intervals thereafter. The clinicopathologic characteristics and nutritional parameters of the educated group (ED) (N = 100) and the non-educated group (NED) (n = 100) were compared. There were no significant differences between the two groups in terms of clinical characteristics and serological parameters. Nutritional parameters, which included body weight loss, body mass index (BMI) change, and prognostic nutritional index (PNI), were also not significantly different between the two groups. Simplified dietary education at regular outpatient clinic visits was ineffective in reducing weight loss after a subtotal gastrectomy. Further research or other methods may be needed to reduce weight loss after a gastrectomy.


Asunto(s)
Gastrectomía , Estado Nutricional , Neoplasias Gástricas/cirugía , Adulto , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pérdida de Peso/fisiología
7.
Artículo en Inglés | MEDLINE | ID: mdl-32674419

RESUMEN

This study evaluates the effect of an integrated health care educational program on several behavioral changes related to environmental health among Laotian students. Students in the experimental group received education concerning environmental health-related issues, including air pollution and chemical exposure. Analyses of covariance (ANCOVA) and paired t-tests were conducted for the statistical analysis of the pre- and post-survey scores. The post-test scores of the experimental group regarding their risk perception and information-seeking behaviors towards air pollution and chemical exposure were higher than those of the control group after controlling for the pre-test scores. Moreover, in the experimental group, the girls' risk perception scores significantly increased after receiving the education, which was not observed in the control group. The risk perception score among non-drinking students also significantly increased after the program. These results indicate that the education program effectively enhanced the students' risk perception, especially that of girls and nondelinquent students.


Asunto(s)
Salud Ambiental , Problema de Conducta , Estudiantes , Adolescente , Educación , Salud Ambiental/educación , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
8.
J Psychoactive Drugs ; 52(1): 46-55, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31888423

RESUMEN

This study examines the relationship between suicidality and smoking behavior. Specifically, it examines how and the degree to which suicide ideation and plan are associated with the probability of being a regular smoker among school-based children. Data come from Lao Student Health Survey (2017), a project funded by the National Research Foundation of Korea. Using primary hierarchically nested data (students clustered in classrooms across schools), we investigate the complex interplay between suicidality and smoking behavior in Lao PDR, a low-income country located in Southeast Asia. Results from fitting two-level random intercept models show that net of controls (e.g., gender, age, parental regulation, self-rated health, household SES), the likelihood of daily smoking is higher among students who have seriously considered committing suicide or have planned a suicide attempt. Controlling for individual-level factors, significant classroom-level contextual effects are also found with respect to peer relations. Finally, we observe a cross-level interaction: the positive association between suicide intent and odds of smoking is weaker in classrooms with better peer relations.


Asunto(s)
Fumar/epidemiología , Estudiantes/psicología , Ideación Suicida , Adolescente , Niño , Femenino , Humanos , Laos/epidemiología , Masculino , Instituciones Académicas , Fumar/psicología , Encuestas y Cuestionarios
9.
ACS Biomater Sci Eng ; 6(5): 2652-2658, 2020 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33463304

RESUMEN

Implantable cardiac monitors have undergone considerable miniaturization. However, they continue to be associated with complications such as infection, bleeding/bruising, and device extrusion or migration. In this paper, we demonstrate the feasibility of using a small, flexible, injectable, subcutaneous microelectrode-based device to record electrocardiograms (ECGs). We describe the fabrication process and demonstrate the ease of insertion of the injectable ECG device in vivo swine model. We also demonstrate our device's high-density channel microelectrode array's ability to detect the P, R, and T waves. The amplitude of these waves showed excellent correlation with distance of the bipolar electrodes used to detect them. Given the success of our initial studies, this device has the potential to improve the safety profile of implantable cardiac monitors and simplify the implantation procedure to allow for placement in a primary care setting.


Asunto(s)
Electrocardiografía , Tejido Subcutáneo , Animales , Diseño de Equipo , Microelectrodos , Porcinos , Tecnología
10.
Artículo en Inglés | MEDLINE | ID: mdl-31635408

RESUMEN

Online hate is a topic that has received considerable interest lately, as online hate represents a risk to self-determination and peaceful coexistence in societies around the globe. However, not much is known about the explanations for adolescents posting or forwarding hateful online material or how adolescents cope with this newly emerging online risk. Thus, we sought to better understand the relationship between a bystander to and perpetrator of online hate, and the moderating effects of problem-focused coping strategies (e.g., assertive, technical coping) within this relationship. Self-report questionnaires on witnessing and committing online hate and assertive and technical coping were completed by 6829 adolescents between 12 and 18 years of age from eight countries. The results showed that increases in witnessing online hate were positively related to being a perpetrator of online hate. Assertive and technical coping strategies were negatively related with perpetrating online hate. Bystanders of online hate reported fewer instances of perpetrating online hate when they reported higher levels of assertive and technical coping strategies, and more frequent instances of perpetrating online hate when they reported lower levels of assertive and technical coping strategies. In conclusion, our findings suggest that, if effective, prevention and intervention programs that target online hate should consider educating young people about problem-focused coping strategies, self-assertiveness, and media skills. Implications for future research are discussed.


Asunto(s)
Adaptación Psicológica , Odio , Internet , Adolescente , Asertividad , Niño , Femenino , Humanos , Masculino , Autoinforme , Encuestas y Cuestionarios
11.
Clin Nutr Res ; 8(1): 74-78, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30746350

RESUMEN

Renal transplantation is one of the renal replacement therapies for patients with end-stage renal disease. The number of patients who receive renal transplantation is continuously increasing, and the use of immunosuppressive drugs that are essential after transplantation requires continuous nutritional management. In the early post-transplantation period, sufficient supply of nutrition in consideration of the increase in metabolic demand is necessary. The long-term nutritional management after transplantation requires nutritional interventions to prevent obesity, hyperlipidemia, hypertension, diabetes, and osteoporosis, which are the adverse effects associated with the use of immunosuppressive drugs. Department of Dietetics in Samsung Medical Center has been engaging with patients to conduct them about initial nutritional assessment and reassessment, description of therapeutic diet, nutrition education for kidney transplantation, and follow-up education after discharge. Nutritional intervention of kidney transplant patients should be carried out according to the post-transplantation period and the nutritional status of the patient. It is necessary to perform patient management according to the planned process.

12.
J Korean Acad Nurs ; 49(6): 783-794, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31932572

RESUMEN

PURPOSE: This study identified factors related to the quality of care in nursing homes, and elicited consensus opinions from experts on nursing homes. METHODS: A Delphi questionnaire was developed based on a review of the literature using the keywords "nursing homes," "workforce," and "quality of care." A total of two Delphi surveys were conducted with 14 experts. The important and urgent factors related to the quality of care for nursing home residents emerged. RESULTS: A consensus was achieved on the important and urgent factors relating to the quality of care. The related factors were grouped into four sections: Organizational Characteristics, Staffing Characteristics, the Long-Term Care Market and Legal and Policy Issues, and Nursing Processes. In total, 23 items were important factors and 26 items were urgent factors relating to the quality of care. In addition, the unanimous advocacy by the experts for increased hours per resident day for registered nurses (RNs, 41 minutes 59 seconds) was much higher than the current hours per resident day of RNs in Korea. CONCLUSION: To provide optimal care for residents in nursing homes in Korea, the mandatory and essential placement of RNs with professional knowledge and skills is paramount.


Asunto(s)
Casas de Salud , Calidad de la Atención de Salud , Anciano , Cuidadores/estadística & datos numéricos , Técnica Delphi , Hogares para Ancianos , Humanos , Personal de Enfermería/estadística & datos numéricos , Cultura Organizacional , República de Corea
13.
J Adolesc ; 69: 180-188, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30390598

RESUMEN

INTRODUCTION: Adolescent pregnancy causes serious problems not only for girls, but also for their family, and society. This study aimed to understand factors related to adolescent pregnancy in low- and middle-income countries using a multilevel approach adopted by Bronfenbrenner's ecological model. METHODS: A total of 11,933 studies published in between 2000 and 2015 were identified in 4 databases. Based on inclusion criteria and risk of bias assessment, a total of 67 articles were retrieved for analysis. RESULTS: Thematic analysis revealed that early marriage, sexual risk behaviors, substance use, family experience of adolescent birth, peer pressure, and lack of sex education and health service increased the hazards of adolescent pregnancy. Communication with parents, school activities, community meetings, laws, and government policies protected adolescents from pregnancy. CONCLUSIONS: Results of this study suggests that the background of adolescents and complex interactions among various factors should be considered for pregnancy. In future research, mixed-method that supplements the methodological weaknesses of previous studies is also recommended.


Asunto(s)
Países en Desarrollo , Embarazo en Adolescencia , Adolescente , Femenino , Humanos , Embarazo , Embarazo en Adolescencia/psicología , Factores Protectores , Factores de Riesgo , Asunción de Riesgos , Conducta Sexual , Factores Socioeconómicos
14.
Artículo en Inglés | MEDLINE | ID: mdl-29970870

RESUMEN

The unique environmental vulnerability of small island developing states (SIDS) is likely to impact negatively on children's health. Children's environmental health indicators (CEHI) are standardized measures that can be used to assess the environmental exposures and their resulting health outcomes in children. This study sought to utilize the United Nations (UN) global Sustainable Development Goals (SDGs), with their associated targets and indicators, as a framework for a CEHI proposal for SIDS. Exposure-side indicators were taken from key themes from the 2012 Rio+20 UN Conference on Sustainable Development, and health-side indicators were selected based on the most significant contributors to the burden of disease in children. The multiple-exposures⁻multiple-effect (MEME) framework was then used to show the relationships between environmental exposures and children's health outcomes. The framework was populated with available data from the World Bank's DataBank. Whilst there was some data available at a population level, major gaps in both exposure-side and health-side indicators were revealed. In order to progress children's environmental health in SIDS, a further piece of work is required to propose a fully prioritized set of exposure-side and health-side CEHIs; based on, but not exclusively linked to, the SDGs.


Asunto(s)
Salud Infantil , Ambiente , Objetivos , Indicadores de Salud , Desarrollo Sostenible , Niño , Humanos , Naciones Unidas
15.
Ann Glob Health ; 83(3-4): 530-540, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29221526

RESUMEN

BACKGROUND: Given that low- and middle-income countries (LMICs) in Asia still have high child mortality rates, improved monitoring using children's environmental health indicators (CEHI) may help reduce preventable deaths by creating healthy environments. OBJECTIVES: Thus, the aim of this study is to build a set of targeted CEHI that can be applied in LMICs in Asia through the CEHI initiative using a common conceptual framework. METHODS: A systematic review was conducted to identify the most frequently used framework for developing CEHI. Due to the limited number of eligible records, a hand search of the reference lists and an extended search of Google Scholar were also performed. Based on our findings, we designed a set of targeted CEHI to address the children's environmental health situation in LMICs in Asia. The Delphi method was then adopted to assess the relevance, appropriateness, and feasibility of the targeted CEHI. FINDINGS: The systematic review indicated that the Driving-Pressure-State-Exposure-Effect-Action framework and the Multiple-Exposures-Multiple-Effects model were the most common conceptual frameworks for developing CEHI. The Multiple-Exposures-Multiple-Effects model was adopted, given that its population of interest is children and its emphasis on the many-to-many relationship. Our review also showed that most of the previous studies covered upper-middle- or high-income countries. The Delphi results validated the targeted CEHI. The targeted CEHI were further specified by age group, gender, and place of residence (urban/rural) to enhance measurability. CONCLUSIONS: Improved monitoring systems of children's environmental health using the targeted CEHI may mitigate the data gap and enhance the quality of data in LMICs in Asia. Furthermore, critical information on the complex interaction between the environment and children's health using the CEHI will help establish a regional environmental children's health action plan, named "The Children's Environment and Health Action Plan for Asia."


Asunto(s)
Asma/epidemiología , Salud Infantil , Países en Desarrollo , Diarrea/epidemiología , Salud Ambiental , Indicadores de Salud , Infecciones del Sistema Respiratorio/epidemiología , Contaminación del Aire Interior , Asia/epidemiología , Mortalidad del Niño , Preescolar , Técnica Delphi , Dengue/epidemiología , Diarrea/mortalidad , Agua Potable , Exposición a Riesgos Ambientales/estadística & datos numéricos , Humanos , Higiene , Lactante , Mortalidad Infantil , Malaria/epidemiología , Infecciones del Sistema Respiratorio/mortalidad , Saneamiento
16.
Behav Pharmacol ; 28(2 and 3-Spec Issue): 199-206, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28234659

RESUMEN

Agitation associated with dementia is frequently reported clinically but has received little attention in preclinical models of dementia. The current study used a 7PA2 CM intracerebroventricular injection model of Alzheimer's disease (AD) to assess acute memory impairment, and a bilateral intrahippocampal (IH) injection model of AD (aggregated Aß1-42 injections) and a bilateral IH injection model of dementia with Lewy bodies (aggregated NAC61-95 injections) to assess chronic memory impairment in the rat. An alternating-lever cyclic-ratio schedule of operant responding was used for data collection, where incorrect lever perseverations measured executive function (memory) and running response rates (RRR) measured behavioral output (agitation). The results indicate that bilateral IH injections of Aß1-42 and bilateral IH injections of NAC61-95 decreased memory function and increased RRRs, whereas intracerebroventricular injections of 7PA2 CM decreased memory function but did not increase RRRs. These findings show that using the aggregated peptide IH injection models of dementia to induce chronic neurotoxicity, memory decline was accompanied by elevated behavioral output. This demonstrates that IH peptide injection models of dementia provide a preclinical screen for pharmacological interventions used in the treatment of increased behavioral output (agitation), which also establish detrimental side effects on memory.


Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Enfermedad por Cuerpos de Lewy/fisiopatología , Trastornos de la Memoria/fisiopatología , Agitación Psicomotora/fisiopatología , Péptidos beta-Amiloides/toxicidad , Animales , Conducta Animal/fisiología , Condicionamiento Operante/fisiología , Modelos Animales de Enfermedad , Función Ejecutiva/fisiología , Hipocampo , Inyecciones Intraventriculares , Masculino , Fragmentos de Péptidos/toxicidad , Ratas , Ratas Sprague-Dawley , alfa-Sinucleína/toxicidad
17.
J Genet Psychol ; 178(1): 44-57, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27805478

RESUMEN

Cyberbullying is one of the negative consequences of online social interaction. The digital environment enables adolescents to engage in online social interaction beyond the traditional physical boundaries of families, neighborhoods, and schools. The authors examined connections to friendship networks in both online and offline settings are related to their experiences as victims, perpetrators, and bystanders of cyberbullying. A comparative face-to-face survey of adolescents (12-15-year-olds) was conducted in Korea (n = 520) and Australia (n = 401). The results reveal that online networks are partially related to cyberbullying in both countries, showing the size of social network sites was significantly correlated with experience cyberbullying among adolescents in both countries. However there were cultural differences in the impact of friendship networks on cyberbullying. The size of the online and offline networks has a stronger impact on the cyberbullying experiences in Korea than it does in Australia. In particular, the number of friends in cliques was positively related to both bullying and victimization in Korea.


Asunto(s)
Conducta del Adolescente/psicología , Acoso Escolar , Víctimas de Crimen/psicología , Comparación Transcultural , Amigos , Relaciones Interpersonales , Adolescente , Australia , Niño , Femenino , Humanos , Internet , Masculino , República de Corea , Apoyo Social , Estudiantes/psicología , Encuestas y Cuestionarios
18.
Free Radic Res ; 50(11): 1188-1199, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27598306

RESUMEN

The degenerative process of the nigral dopamine(DA)rgic neurons in Parkinson's disease (PD) involves both oxidative stress and neuroinflammation. In the present study, we aimed at developing a novel antioxidant and anti-inflammatory agent for PD therapy. Toward this end, we screened a novel focused library of isothiocyanate derivatives that we have generated for an anti-inflammatory property. We obtained a novel compound ITC-57 and found that ITC-57 effectively induced gene expression of the antioxidant enzymes NAD(P)H quinone oxidoreductase-1, the catalytic and modulatory subunits of glutamylcysteine ligase, and HO-1 in DAergic neuronal CATH.a cells and protected CATH.a cells from oxidative damages. The compound also induced the same antioxidant enzymes in microglial BV-2 cells and suppressed the production of the proinflammatory molecules nitric oxide, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in lipopolysaccharide-activated BV-2 cells. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-elicited mouse model of PD, ITC-57 protected the DAergic neurons from degeneration, induced HO-1, lowered TNF-α, and suppressed microglial activation in the nigra. Furthermore, ITC-57 prevented the PD-associated motor deficits from occurring. Taken together, ITC-57 would be useful toward development of a disease-modifying therapy for PD.


Asunto(s)
Isotiocianatos/farmacología , Enfermedad de Parkinson/metabolismo , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Muerte Celular , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo
19.
Neuropharmacology ; 100: 124-30, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26025659

RESUMEN

Bexarotene has been reported to reduce brain amyloid-ß (Aß) levels and to improve cognitive function in transgenic mouse models of Alzheimer's disease (AD). Four groups failed to fully replicate the primary results but the original authors claimed overall support for the general conclusions. Because of its potential clinical importance, the current work studied the effects of bexarotene using two animal species and highly relevant paradigms. Rats were tested for the ability of bexarotene to prevent changes induced by an Aß challenge in the form intracerebroventricular (i.c.v) administration of 7PA2 conditioned medium (7PA2 CM) which contains high levels of Aß species. Bexarotene had no effect on the long-term potentiation of evoked extracellular field excitatory postsynaptic potentials induced by i.c.v. 7PA2 CM. It also had no effect following subcutaneous administration of 2, 5, 10 and 15 mg/kg on behavioral/cognitive impairment using an alternating-lever cyclic-ratio schedule of operant responding in the rat. The effects of bexarotene were further tested using the APPSwFILon, PSEN1*M146L*L286V transgenic mouse model of AD, starting at the time Aß deposits first begin to develop. Mice were sacrificed after 48 days of exposure to 100 mg bexarotene per day. No significant difference between test and control mice was found using a water-maze test, and no significant difference in the number of Aß deposits in cerebral cortex, using two different antibodies, was apparent. These results question the potential efficacy of bexarotene for AD treatment, even if instigated in the preclinical period prior to the onset of cognitive deficits reported for human AD. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Región CA1 Hipocampal/efectos de los fármacos , Tetrahidronaftalenos/administración & dosificación , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/prevención & control , Péptidos beta-Amiloides/toxicidad , Animales , Bexaroteno , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiopatología , Células CHO , Condicionamiento Operante/efectos de los fármacos , Cricetulus , Medios de Cultivo Condicionados , Modelos Animales de Enfermedad , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Transgénicos , Ratas , Ratas Sprague-Dawley
20.
Neuropharmacology ; 92: 170-82, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25637092

RESUMEN

ß-amyloid1-42 (Aß1-42) is a major endogenous pathogen underlying the aetiology of Alzheimer's disease (AD). Recent evidence indicates that soluble Aß oligomers, rather than plaques, are the major cause of synaptic dysfunction and neurodegeneration. Small molecules that suppress Aß aggregation, reduce oligomer stability or promote off-pathway non-toxic oligomerization represent a promising alternative strategy for neuroprotection in AD. MRZ-99030 was recently identified as a dipeptide that modulates Aß1-42 aggregation by triggering a non-amyloidogenic aggregation pathway, thereby reducing the amount of intermediate toxic soluble oligomeric Aß species. The present study evaluated the relevance of these promising results with MRZ-99030 under pathophysiological conditions i.e. against the synaptotoxic effects of Aß oligomers on hippocampal long term potentiation (LTP) and two different memory tasks. Aß1-42 interferes with the glutamatergic system and with neuronal Ca(2+) signalling and abolishes the induction of LTP. Here we demonstrate that MRZ-99030 (100-500 nM) at a 10:1 stoichiometric excess to Aß clearly reversed the synaptotoxic effects of Aß1-42 oligomers on CA1-LTP in murine hippocampal slices. Co-application of MRZ-99030 also prevented the two-fold increase in resting Ca(2+) levels in pyramidal neuron dendrites and spines triggered by Aß1-42 oligomers. In anaesthetized rats, pre-administration of MRZ-99030 (50 mg/kg s.c.) protected against deficits in hippocampal LTP following i.c.v. injection of oligomeric Aß1-42. Furthermore, similar treatment significantly ameliorated cognitive deficits in an object recognition task and under an alternating lever cyclic ratio schedule after the i.c.v. application of Aß1-42 and 7PA2 conditioned medium, respectively. Altogether, these results demonstrate the potential therapeutic benefit of MRZ-99030 in AD.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Trastornos del Conocimiento , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Potenciación a Largo Plazo/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/toxicidad , Animales , Calcio/metabolismo , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/metabolismo , Condicionamiento Operante/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Técnicas In Vitro , Inyecciones Intraventriculares , Inositol/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Putamen/efectos de los fármacos , Putamen/metabolismo , Ratas , Ratas Sprague-Dawley , Reconocimiento en Psicología/efectos de los fármacos
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