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1.
Pharmacy (Basel) ; 11(2)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37104082

RESUMO

The use of pharmacogenetics to optimize pharmacotherapy is growing rapidly. This study evaluates the feasibility and operability of a collaborative circuit involving hospital and community pharmacists to implement clopidogrel pharmacogenetics in Barcelona, Catalonia, Spain. We aimed to enroll patients with a clopidogrel prescription from cardiologists at the collaborating hospital. Community pharmacists collected patients' pharmacotherapeutic profiles and saliva samples, which were then sent to the hospital for CYP2C19 genotyping. Hospital pharmacists collated the obtained data with patients' clinical records. Data were analyzed jointly with a cardiologist to assess the suitability of clopidogrel. The provincial pharmacists' association coordinated the project and provided IT and logistic support. The study began in January 2020. However, it was suspended in March 2020 due to the COVID-19 pandemic. At that moment, 120 patients had been assessed, 16 of whom met the inclusion criteria and were enrolled in the study. The processing of samples obtained before the pandemic had an average delay of 13.8 ± 5.4 days. A total of 37.5% patients were intermediate metabolizers and 18.8% were ultrarapid metabolizers. No poor metabolizers were detected. Pharmacists rated their experience with a 7.3 ± 2.7 likelihood of recommending that fellow pharmacists participate. The net promoter score among participating pharmacists was +10%. Our results show that the circuit is feasible and operable for further initiatives.

2.
J Intern Med ; 292(1): 116-126, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35184348

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is an independent predictor of death in patients with human immunodeficiency virus (HIV) infection. HIV is the leading cause of PAH (HIV-PAH) worldwide. AIMS: We described the characteristics, treatment patterns, and prognosis of a cohort of HIV-PAH patients and compared them with those of an equivalent cohort of patients with idiopathic/familial PAH (IPAH/FPAH). METHODS: We retrospectively analysed and compared the demographic, clinical, and treatment data from patients with HIV-PAH and those with IPAH/FPAH in the Spanish PAH registry (REHAP) from 1998 to 2018. The HIV-PAH overall survival (OS) rate up to 5 years was compared to the age- and sex-matched IPAH/FPAH population. Changes in treatment patterns in patients with HIV-PAH after 2010 and their effects on OS were also analysed. RESULTS: Compared to those with IPAH/FPAH (n = 739), patients with HIV-PAH (n = 132) were younger, mainly men, and had a better functional status. The clinical presentation, haemodynamics, and respiratory function were similar between the groups. Parenteral drug use was the most common mode of HIV transmission. Approximately 11% of patients with HIV-PAH did not receive PAH-targeted therapy. The age- and sex-adjusted 5-year OS rate from diagnosis was 74.0% for patients with HIV-PAH and 68.7% for those with IPAH (p < 0.159). During/after 2010, 23% of patients with IPAH/FPAH received upfront dual oral combination, while oral monotherapy remained the main first-line treatment in patients with HIV-PAH. The overall OS rate remained stable. CONCLUSIONS: Patients with HIV-PAH were predominantly young men. The short-term prognosis is similar to that of age- and sex-matched patients with IPAH/FPAH, despite a better functional status. Oral monotherapy remains the preferred first-line treatment in the current cohorts.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Hipertensão Pulmonar Primária Familiar , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Masculino , Prognóstico , Hipertensão Arterial Pulmonar/epidemiologia , Hipertensão Arterial Pulmonar/etiologia , Sistema de Registros , Estudos Retrospectivos
3.
FASEB J ; 34(9): 11816-11837, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32666604

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.


Assuntos
Biomarcadores/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Ácidos Graxos/metabolismo , Terapia Genética/métodos , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/terapia , Animais , Carnitina O-Palmitoiltransferase/genética , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/etiologia , Obesidade/metabolismo , Oxirredução , Triglicerídeos/metabolismo
4.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 38(5): 234-237, mayo 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-201093

RESUMO

Para implementar la profilaxis preexposición (PrEP) para el VIH en España deben barajarse los diferentes modelos que se ajusten a nuestro Sistema Nacional de Salud. Las experiencias de países con entorno similar permiten adelantar sus beneficios y sus defectos antes de su implementación. Los modelos de implementación posibles para el circuito de prescripción-seguimiento-dispensación podrían implicar hospitales, centros de ITS, centros de Atención Primaria y farmacia comunitarias. Por un lado, el circuito hospitalario es el menos eficiente y presumiblemente no podría satisfacer la potencial demanda, aunque podría ser implantado inmediatamente. Por otro lado, la accesibilidad se ampliaría si su prescripción y dispensación tuvieran lugar desde la Atención Primaria y la farmacia comunitaria. La incorporación de centros de ITS públicos y comunitarios sería la mejor opción para atraer a población no frecuentadora del sistema sanitario general y su gestión compartida con Atención Primaria permitiría el acceso a la PrEP en el territorio nacional


To implement HIV pre-exposure prophylaxis (PrEP) in Spain, several possible models fitting the Spanish National Health System must be considered. The experience of other countries with a similar background let us foresee their benefits and their defects before implementing them. Possible implementation models for prescription-follow-up-dispensing circuits may involve hospitals, STI clinics or primary care centres and community pharmacies. On the one hand, a hospital-based circuit is the least effective of them all and it may not satisfy the potential demand, even though it could be deployed immediately. On the other hand, accessibility would increase with PrEP prescription in Primary care and dispensing by community pharmacists. Involvement of community-based STI clinics and publicly-funded STI clinics would be the best option to attract the population not frequenting the general health system, and co-management with Primary Care teams would ensure nation-wide access to PrEP


Assuntos
Humanos , Profilaxia Pré-Exposição/métodos , Modelos de Assistência à Saúde , Infecções por HIV/prevenção & controle , Espanha
5.
Rev. psicol. clín. niños adolesc ; 7(2): 16-21, mayo 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-193689

RESUMO

Fear of darkness is highly prevalent and stable in children and often ends up becoming a specific situational phobia. The aim of this study is to analyze the feasibility of adapting and applying it through a Virtual Reality (VR) tool by nonexpert therapists. A pre-experimental study was carried out with six participants between the ages of 8 and 12 years old using pre- and posttreatment scales for assessing the fear of darkness. Statistically significant differences with large effects were found in all posttreatment measures: EMO (Roshenthal's r = 0.64), WCDAN (r = 0.52), and Global item of current fear of darkness (r = 0.59). Using the Reliable Change Index (RCI) as a measure of clinically significant change, four participants improved satisfactorily, one acceptably, and the other did not improve. The results support the feasibility of using an adapted VR program to treat fear of darkness without being an expert therapist. However, more detailed experimental studies need to be carried out in order to analyze its efficacy


El miedo a la oscuridad es muy frecuente y estable en los niños y, a menudo, termina convirtiéndose en una fobia situacional específica. El objetivo de este estudio es analizar la viabilidad de adaptarlo y aplicarlo a través de una herramienta de realidad virtual (RV) por terapeutas no expertos. Se ha llevado a cabo un estudio pre-experimental con seis participantes de 8 a 12 años de edad utilizando escalas de pre y postratamiento para evaluar el miedo a la oscuridad. Se han encontrado diferencias estadísticamente significativas con tamaños del efecto grandes en todas las medidas posteriores al tratamiento: EMO (Roshenthal's r = 0.64), WCDAN (r = 0.52), e ítem global del miedo actual a la oscuridad (r = 0.59). Al usar el Índice de Cambio Fiable (ICF) como una medida del cambio clínicamente significativo, cuatro participantes mejoraron satisfactoriamente, uno aceptablemente, y el otro no mejoró. Los resultados apoyan la viabilidad de utilizar un programa de RV adaptado para tratar el miedo a la oscuridad sin necesidad de un terapeuta experto. Sin embargo, se necesitan estudios experimentales más detallados para analizar su eficacia


Assuntos
Humanos , Masculino , Feminino , Criança , Transtornos Fóbicos/terapia , Medo/psicologia , Escuridão , Realidade Virtual , Reprodutibilidade dos Testes
6.
Enferm Infecc Microbiol Clin (Engl Ed) ; 38(5): 234-237, 2020 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31279586

RESUMO

To implement HIV pre-exposure prophylaxis (PrEP) in Spain, several possible models fitting the Spanish National Health System must be considered. The experience of other countries with a similar background let us foresee their benefits and their defects before implementing them. Possible implementation models for prescription-follow-up-dispensing circuits may involve hospitals, STI clinics or primary care centres and community pharmacies. On the one hand, a hospital-based circuit is the least effective of them all and it may not satisfy the potential demand, even though it could be deployed immediately. On the other hand, accessibility would increase with PrEP prescription in Primary care and dispensing by community pharmacists. Involvement of community-based STI clinics and publicly-funded STI clinics would be the best option to attract the population not frequenting the general health system, and co-management with Primary Care teams would ensure nation-wide access to PrEP.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Instituições de Assistência Ambulatorial , Infecções por HIV/prevenção & controle , Humanos , Atenção Primária à Saúde , Espanha
7.
Digit Med ; 6(2): 53-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-35663234

RESUMO

On March 12, 2020, with more than 20,000 confirmed cases and almost 1000 deaths in the European Region, the World Health Organization classified the COVID-19 outbreak as a pandemic. As of August 15, 2020, there are 21.5 million confirmed cases of COVID-19 and over 766,000 deaths from the virus, worldwide. Most governments have imposed quarantine measures of varied degrees of strictness on their populations in attempts to stall the spread of the infection in their communities. However, the isolation may have inflicted long-term psychological injury to the general population and, in particular, to at-risk groups such as the elderly, the mentally ill, children, and frontline healthcare staff. In this article, we offer the most up-to-date review of the effects of COVID-19 confinement on all the disorders listed in the Diagnostic and Statistical Manual of Mental Disorders. We make data-driven predictions of the impact of COVID-19 confinement on mental health outcomes and discuss the potential role of telemedicine and virtual reality in mental health screening, diagnosis, treatment, and monitoring, thus improving the above outcomes in such a difficult time.

8.
Pharm Pract (Granada) ; 17(3): 1455, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592287

RESUMO

BACKGROUND: Skin cancer incidence is increasing alarmingly, despite current efforts trying to improve its early detection. Community pharmacists have proven success in implementing screening protocols for a number of diseases because of their skills and easy access. OBJECTIVE: To evaluate the prevalence of skin cancer risk factors and the photoprotection habits with a questionnaire in community pharmacy users. METHODS: A research group consisting of pharmacists and dermatologists conducted a descriptive cross-sectional study to assess photoprotection habits and skin cancer risk factors by using a validated questionnaire in 218 community pharmacies in Barcelona from May 23rd to June 13th 2016. All participants received health education on photoprotection and skin cancer prevention. Patients with ≥1 skin cancer risk factor were referred to their physician, as they needed further screening of skin cancer. RESULTS: A total of 5,530 participants were evaluated. Of those, only 20.2% participants had received a total body skin examination for skin cancer screening in the past by a physician and 57.1% reported using a SPF 50+ sunscreen. 53.9% participants presented ≥1 skin cancer risk factor: 11.8% participants reported having skin cancer familial history and 6.2% reported skin cancer personal history; pharmacists found ≥10 melanocytic nevi in 43.8% participants and chronically sun-damaged skin in 21.4%. Lesions suspicious for melanoma were reported in 10.9% of the participants and urgent dermatological evaluation was recommended. CONCLUSIONS: Pharmacists can detect people with skin cancer risk factors amongst their users. This intervention can be considered in multidisciplinary strategies of skin cancer screening.

9.
Pharm. pract. (Granada, Internet) ; 17(3): 0-0, jul.-sept. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-188112

RESUMO

Background: Skin cancer incidence is increasing alarmingly, despite current efforts trying to improve its early detection. Community pharmacists have proven success in implementing screening protocols for a number of diseases because of their skills and easy access. Objective: To evaluate the prevalence of skin cancer risk factors and the photoprotection habits with a questionnaire in community pharmacy users. Methods: A research group consisting of pharmacists and dermatologists conducted a descriptive cross-sectional study to assess photoprotection habits and skin cancer risk factors by using a validated questionnaire in 218 community pharmacies in Barcelona from May 23rd to June 13th 2016. All participants received health education on photoprotection and skin cancer prevention. Patients with ≥1 skin cancer risk factor were referred to their physician, as they needed further screening of skin cancer. Results: A total of 5,530 participants were evaluated. Of those, only 20.2% participants had received a total body skin examination for skin cancer screening in the past by a physician and 57.1% reported using a SPF 50+ sunscreen. 53.9% participants presented ≥1 skin cancer risk factor: 11.8% participants reported having skin cancer familial history and 6.2% reported skin cancer personal history; pharmacists found ≥10 melanocytic nevi in 43.8% participants and chronically sun-damaged skin in 21.4%. Lesions suspicious for melanoma were reported in 10.9% of the participants and urgent dermatological evaluation was recommended. Conclusions: Pharmacists can detect people with skin cancer risk factors amongst their users. This intervention can be considered in multidisciplinary strategies of skin cancer screening


No disponible


Assuntos
Humanos , Serviços Comunitários de Farmácia/organização & administração , Neoplasias Cutâneas/epidemiologia , Proteção Radiológica/estatística & dados numéricos , Protetores Solares/farmacocinética , Radiação Solar/efeitos adversos , Detecção Precoce de Câncer/métodos , Estudos Transversais , Fatores de Risco , Variação Biológica da População
10.
Sci Rep ; 8(1): 6997, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29725060

RESUMO

Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments.


Assuntos
Autofagia , Carnitina O-Palmitoiltransferase/metabolismo , Glucose/metabolismo , Células-Tronco Mesenquimais/fisiologia , Trifosfato de Adenosina/metabolismo , Sobrevivência Celular , Células Cultivadas , Metabolismo Energético , Ácidos Graxos/metabolismo , Humanos , Lipólise , Oxirredução
11.
Mol Neurobiol ; 55(9): 7216-7228, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29396649

RESUMO

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.


Assuntos
Córtex Cerebral/metabolismo , Ácidos Graxos/metabolismo , Grelina/farmacologia , Ácido gama-Aminobutírico/metabolismo , Animais , Carnitina O-Palmitoiltransferase/metabolismo , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Citratos/metabolismo , Ciclo do Ácido Cítrico/efeitos dos fármacos , Deleção de Genes , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ácidos Cetoglutáricos/metabolismo , Metaboloma/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxirredução
12.
Eur J Med Chem ; 131: 207-221, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28324785

RESUMO

C75 is a synthetic anticancer drug that inhibits fatty acid synthase (FAS) and shows a potent anorexigenic side effect. In order to find new cytotoxic compounds that do not impact food intake, we synthesized a new family of C75 derivatives. The most promising anticancer compound among them was UB006 ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one). The effects of this compound on cytotoxicity, food intake and body weight were studied in UB006 racemic mixture and in both its enantiomers separately. The results showed that both enantiomers inhibit FAS activity and have potent cytotoxic effects in several tumour cell lines, such as the ovarian cell cancer line OVCAR-3. The (-)-UB006 enantiomer's cytotoxic effect on OVCAR-3 was 40-fold higher than that of racemic C75, and 2- and 38-fold higher than that of the racemic mixture and its opposite enantiomer, respectively. This cytotoxic effect on the OVCAR-3 cell line involves mechanisms that reduce mitochondrial respiratory capacity and ATP production, DDIT4/REDD1 upregulation, mTOR activity inhibition, and caspase-3 activation, resulting in apoptosis. In addition, central and peripheral administration of (+)-UB006 or (-)-UB006 into rats and mice did not affect food intake or body weight. Altogether, our data support the discovery of a new potential anticancer compound (-)-UB006 that has no anorexigenic side effects.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Graxo Sintases/antagonistas & inibidores , Furanos/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ingestão de Alimentos/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Ácido Graxo Sintases/metabolismo , Furanos/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley
13.
Adipocyte ; 5(2): 98-118, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27386151

RESUMO

Obesity has reached epidemic proportions, leading to severe associated pathologies such as insulin resistance, cardiovascular disease, cancer and type 2 diabetes. Adipose tissue has become crucial due to its involvement in the pathogenesis of obesity-induced insulin resistance, and traditionally white adipose tissue has captured the most attention. However in the last decade the presence and activity of heat-generating brown adipose tissue (BAT) in adult humans has been rediscovered. BAT decreases with age and in obese and diabetic patients. It has thus attracted strong scientific interest, and any strategy to increase its mass or activity might lead to new therapeutic approaches to obesity and associated metabolic diseases. In this review we highlight the mechanisms of fatty acid uptake, trafficking and oxidation in brown fat thermogenesis. We focus on BAT's morphological and functional characteristics and fatty acid synthesis, storage, oxidation and use as a source of energy.

14.
PLoS One ; 11(7): e0159399, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27438137

RESUMO

The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders.


Assuntos
Carnitina O-Palmitoiltransferase/genética , Metabolismo Energético/genética , Mitocôndrias/metabolismo , Obesidade/genética , Proteína Desacopladora 1/genética , Adipócitos Marrons/metabolismo , Adipócitos Marrons/patologia , Animais , Carnitina O-Palmitoiltransferase/biossíntese , Diferenciação Celular/genética , Regulação Enzimológica da Expressão Gênica , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Lipólise/genética , Mitocôndrias/patologia , Obesidade/metabolismo , Obesidade/patologia , Ratos , Termogênese/genética , Proteína Desacopladora 1/biossíntese
15.
Am J Physiol Endocrinol Metab ; 308(9): E756-69, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25714670

RESUMO

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.


Assuntos
Adipócitos/metabolismo , Ácidos Graxos/metabolismo , Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/farmacologia , Macrófagos/metabolismo , Células 3T3-L1 , Adulto , Idoso , Animais , Estudos de Coortes , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Obesidade/metabolismo , Oxirredução , Triglicerídeos/metabolismo
16.
PLoS One ; 9(5): e97195, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24819600

RESUMO

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid ß-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.


Assuntos
Carnitina O-Palmitoiltransferase/genética , Hiperfagia/genética , Hiperfagia/metabolismo , Metabolismo dos Lipídeos/genética , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Regulação do Apetite/genética , Carnitina O-Palmitoiltransferase/metabolismo , Dependovirus/genética , Ingestão de Alimentos/genética , Expressão Gênica , Vetores Genéticos/genética , Hiperglicemia/enzimologia , Hiperglicemia/genética , Hiperfagia/enzimologia , Resistência à Insulina/genética , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Obesidade/enzimologia , Obesidade/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Núcleo Hipotalâmico Ventromedial/fisiopatologia
17.
Antioxid Redox Signal ; 19(3): 269-84, 2013 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-22900819

RESUMO

SIGNIFICANCE: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. RECENT ADVANCES: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. CRITICAL ISSUES: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. FUTURE DIRECTIONS: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.


Assuntos
Ácidos Graxos/metabolismo , Mitocôndrias/metabolismo , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Humanos , Hipotálamo/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Mitocôndrias/efeitos dos fármacos , Obesidade/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos
18.
Rev Esp Cardiol ; 63(5): 583-96, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20450852

RESUMO

Recently, our view of pulmonary hypertension has been changed by the significant progress made in understanding the pathobiology, epidemiology and prognosis of the disease. The increasing number of different conditions now associated with pulmonary hypertension and the appearance of new diagnostic techniques have led to a need for a systematic diagnostic approach and a new disease classification. This review article presents an update on developments in the epidemiology and pathobiology of pulmonary hypertension, on changes in the clinical classification of the disease, and on alterations in the diagnostic algorithm. In addition, it contains detailed descriptions of the treatment recommended for patients in whom an elevated systolic pulmonary pressure is discovered on echocardiography, of the differential diagnosis of pulmonary arterial hypertension and pulmonary hypertension associated with left heart disease, and of multifactorial approaches to determining prognosis, which are three of the most actively debated topics today. Finally, a care program for patients with pulmonary arterial hypertension is proposed.


Assuntos
Hipertensão Pulmonar/diagnóstico , Humanos , Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Prognóstico , Artéria Pulmonar/patologia
20.
Int Microbiol ; 7(1): 19-25, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15179603

RESUMO

Microbial mats arising in the sand flats of the Ebro Delta (Tarragona, Spain) were investigated during the summer season, when the community was highly developed. These mats are composed of three pigmented layers of phototrophic organisms, an upper brown layer mainly composed of Lyngbya aestuarii and diatoms, an intermediate green layer of the cyanobacterium Microcoleus chthonoplastes, and an underlying pink layer of a so-far unidentified purple sulfur bacterium. In the photic zone, oxygenic phototrophs constitute about 58% of total photosynthetic biomass, measured as biovolume, and anoxygenic phototrophs represent 42%. Diatoms constitute 11.8% of the oxygenic biomass, M. chthonoplastes 61.2%, and L. aestuarii and coccoid cyanobacteria 20.6 and 6.4%, respectively. In this laminated community, organic matter has an autochthonous origin, and photosynthesis is the most important source of organic carbon. Oxygen production reaches up to 27.2 mmol O(2) m(-2) h(-1), measured at 1000 microE m(-2) s(-1) light intensity, whereas oxidation of sulfide in the light has been calculated to be 18.6 mmol S m(-2) h(-1). This amount represents 26% of the total photosynthetic production in terms of photoassimilated carbon, demonstrating the important role of anoxygenic phototrophs as primary producers in the pink layer of Ebro Delta microbial mats.


Assuntos
Biomassa , Cianobactérias/crescimento & desenvolvimento , Microbiologia da Água , Bacterioclorofila A/análise , Cianobactérias/classificação , Cianobactérias/isolamento & purificação , Diatomáceas/crescimento & desenvolvimento , Diatomáceas/isolamento & purificação , Luz , Oxirredução , Pigmentos Biológicos/análise , Espanha , Sulfetos/metabolismo
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