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1.
Front Endocrinol (Lausanne) ; 15: 1350154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577571

RESUMO

Introduction: Progesterone-primed cycles effectively suppress the pituitary LH surge during ovarian stimulation in oocyte donors and in the infertile population. Particularly in oocyte donors, the use of synthetic progesterone (progestins) has been explored in prospective clinical trials, showing mixed results. This trial was designed to determine whether the use of micronized natural progesterone is as effective as the GnRH-antagonist protocol in terms of the number of mature oocytes (MII) retrieved in oocyte donation cycles as a primary outcome, and it also aims to explore the corresponding results in recipients as a secondary outcome. Methods: We propose a prospective, open-label, non-inferiority clinical trial to compare a novel approach for oocyte donors with a control group, which follows the standard ovarian stimulation protocol used in our institution. A total of 150 donors (75 in each group) will be recruited and randomized using a computer algorithm. After obtaining informed consent, participants will be randomly assigned to one of two ovarian stimulation protocols: either the standard GnRH antagonist or the oral micronized natural progesterone protocol. Both groups will receive recombinant gonadotropins tailored to their antral follicle count and prior donation experiences, if any. The primary outcome is the number of mature metaphase II (MII) oocytes. Secondary measures include treatment duration, pregnancy outcomes in recipients, as well as the economic cost per MII oocyte obtained in each treatment regimen. Analyses for the primary outcome will be conducted in both the intention-to-treat (ITT) and per-protocol (PP) populations. Each donor can participate only once during the recruitment period. The estimated duration of the study is six months for the primary outcome and 15 months for the secondary outcomes. Discussion: The outcomes of this trial have the potential to inform evidence-based adjustments in the management of ovarian stimulation protocols for oocyte donors. Clinical trial registration: ClinicalTrials.gov, identifier, NCT05954962.


Assuntos
Antagonistas de Hormônios , Progesterona , Feminino , Humanos , Gravidez , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/uso terapêutico , Indução da Ovulação/métodos , Progestinas , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Hernia ; 25(6): 1519-1527, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33009962

RESUMO

PURPOSE: To evaluate and detail the management of a difficult, long-term, open abdomen in a resource constraint setting with the use of Hydrocolloid dressing. METHOD: An observational retrospective study was conducted at a single level-1 trauma center. Over a 5-year period, all the open abdomen patients were evaluated and the cohorts who were treated with Hydrocolloid dressings were described in detail from their admission to their discharge. RESULTS: During this period, there were 147 open abdomens. 7.5% (11) patients required long-term open abdomen management, in which Hydrocolloid dressing was utilized. Of this group, there were no entero/colonic-atmospheric fistulas, and there was either de-novo complete skin coverage, successful skin graft placement, or definitive abdominal wall repair in all the patients. De-novo complete skin coverage took an average of 7.4 months. All the patients were discharged home after an average of 107 days hospitalized. CONCLUSION: Despite not being an optimal management of an open abdomen, there are always a small group of these patients who lose abdominal domain, are critically ill or injured, and have prolonged hospitalization with an open abdomen. In this cohort, and especially in resource constraint settings, Hydrocolloid dressing is a cost-efficient, simple, and effective method to treat the 'long-term' open abdomens.


Assuntos
Curativos Hidrocoloides , Fístula Intestinal , Abdome/cirurgia , Herniorrafia , Humanos , Estudos Retrospectivos , Cicatrização
5.
Sci Adv ; 6(35): eabb3308, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32923637

RESUMO

Understanding the dynamics of circulating tumor cell (CTC) behavior within the vasculature has remained an elusive goal in cancer biology. To elucidate the contribution of hydrodynamics in determining sites of CTC vascular colonization, the physical forces affecting these cells must be evaluated in a highly controlled manner. To this end, we have bioprinted endothelialized vascular beds and perfused these constructs with metastatic mammary gland cells under physiological flow rates. By pairing these in vitro devices with an advanced computational flow model, we found that the bioprinted analog was readily capable of evaluating the accuracy and integrated complexity of a computational flow model, while also highlighting the discrete contribution of hydrodynamics in vascular colonization. This intersection of these two technologies, bioprinting and computational simulation, is a key demonstration in the establishment of an experimentation pipeline for the understanding of complex biophysical events.

6.
J Investig Allergol Clin Immunol ; 30(4): 229-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31932268

RESUMO

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Fígado/metabolismo , Pele/patologia , Algoritmos , Alopurinol/efeitos adversos , Antibacterianos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Comorbidade , Consenso , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Eosinofilia , Prova Pericial , Humanos , Leucocitose , Fígado/patologia , Fatores de Risco , Espanha/epidemiologia
7.
Arq. bras. med. vet. zootec. (Online) ; 72(1): 191-198, Jan.-Feb. 2020. tab, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-1088923

RESUMO

O objetivo deste trabalho foi mapear e descrever a ocorrência de roedores e seus ectoparasitas nas regiões norte do departamento de La Paz, Bolívia. De abril a maio e julho a agosto de 2017, 80 indivíduos da espécie Oligoryzomys microtis foram capturados em armadilhas vivas. Uma amostra aleatória de 36 indivíduos foi analisada quanto à presença de ectoparasitas, encontrando um total de 458 ectoparasitas. Os roedores foram capturados em dois tipos de ambientes: floresta secundária e áreas cultivadas, sendo a área cultivada a área com maior captação de roedores. Dos ectoparasitas, Laelaps sp. foi o gênero com maior abundância e Mysolaelaps sp. o mais prevalente; o gênero Polygenis sp. é aparentemente descrito pela primeira vez na selva amazônica, exigindo estudos adicionais para entender melhor os patógenos que são transmitidos no parasitismo desta pulga em roedores devido à sua importância no ecossistema e para a saúde pública.(AU)


The objective of this work was to map and describe the occurrence of rodents and their ectoparasites in regions to the North of the department of La Paz in Bolivia. From April to May and July to August 2017, 80 Oligoryzomys microtis rodents were captured and 36 random samples of their ectoparasites were analyzed, totaling 458 ectoparasites. Rodents were captured in two types of environments: secondary forest and crops areas, being the second one with greater amount of capture of rodents. Among the ectoparasites, Laelaps sp was the genus with the highest abundance and Mysolaelaps sp with the highest prevalence; the genus Polygenis sp is apparently described for the first time in the Amazon rainforest, requiring more studies to better understand the pathogens transmitted in the parasitism of this flea in rodents due to their importance in the ecosystem and public health.(AU)


Assuntos
Animais , Parasitos , Roedores/parasitologia , Ectoparasitoses/veterinária , Bolívia
8.
Colloids Surf B Biointerfaces ; 175: 116-125, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30529817

RESUMO

The use of nanovectors in several medicinal treatments has reached a great importance in the last decade. Some drugs need to be protected to increase their lifetimes in the blood flow, to avoid degradation, to be delivered into target cells or to decrease their side effects. The goal of this work was to design and prepare nanovectors formed by novel surfactants derived from the [Ru(bpy)3]2+ complex. These amphiphilic molecules are assembled to form metallomicelles which can act as pharmaceutical agents and, at the same time, as nanovectors for several drugs. TEM images showed a structural transition from spherical to elongated micelles when the surfactant concentration increased. Fluorescence microscopy confirmed the internalization of these metallomicelles into diverse cell lines and cytotoxicity assays demonstrated specificity for some human cancer cells. The encapsulation of various antibiotics was carried out as well as a thorough study about the DNA condensation by the metallomicelles. To the best of our knowledge, applications of these metallomicelles have not been shown in the literature yet.


Assuntos
Complexos de Coordenação/química , Micelas , Nanopartículas/química , Rutênio/química , Células A549 , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Composição de Medicamentos , Células Hep G2 , Humanos , Células MCF-7 , Microscopia de Força Atômica , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Rutênio/farmacologia
9.
Arch Soc Esp Oftalmol ; 92(3): 145-148, 2017 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27402450

RESUMO

CLINICAL CASE: A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. DISCUSSION: Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases.


Assuntos
Retinite por Citomegalovirus/etiologia , Infiltração Leucêmica , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Retina/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Citarabina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Idarubicina/administração & dosagem , Infiltração Leucêmica/tratamento farmacológico , Infiltração Leucêmica/radioterapia , Papiledema/etiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/radioterapia , Recidiva , Hemorragia Retiniana/etiologia , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
11.
World J Emerg Surg ; 11: 25, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27307785

RESUMO

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

12.
Bol. Asoc. Argent. Odontol. Niños ; 44(2): 18-22, sept.-dic. 2015. ilus
Artigo em Espanhol | LILACS | ID: lil-786706

RESUMO

El objetivo de este trabajo es presentar los resultados obtenidos después del tratamiento de una pieza permanente joven con diagnóstico de necrosis pulpar tratada con el método de revascularización como opción alterantiva al tratamiento tradicional de apexificación con hidróxido de calcio. La técnica consiste en la desinfección del conducto radicular para posteriormente inducir la formación de un coágulo sanguíneo que actúe como soporte para sustentar a las células madre periféricas de la sangre y del tejido local, lo que crearía las condiciones de revascularización. Se presentan los controles clínicos-radiográficos del seguimiento a 15 mesews, donde se observa el cierre apical, junto con el crecimiento en longitud y ancho radicular, producto de la revascularización pulpar, logrando semejanza anatómica con una pieza dentaria homóloga


Assuntos
Humanos , Feminino , Criança , Células-Tronco/fisiologia , Dentição Permanente , Necrose da Polpa Dentária/terapia , Cicatrização/fisiologia , Raiz Dentária/fisiologia , Tecido Periapical/irrigação sanguínea
13.
Rev. bras. plantas med ; 17(3): 480-494, Jul-Sep/2015. tab
Artigo em Espanhol | MOSAICO - Saúde integrativa, LILACS | ID: lil-752558

RESUMO

RESUMO O objetivo deste estudo foi determinar o potencial de plantas que crecem na região de Coquimbo, no controle de nematódeos gastrintestinais em caprinos. Nós usamos uma abordagem não-experimental para validar a eficácia potencial das plantas medicinais como anti-helmínticos. Esta validação foi realizada com base em uma revisão da extensa literatura consultada a respeito de plantas medicinais. Determinou-se o um potencial de eficácia das plantas, da consistência das informações sobre o uso tradicional, os compostos presentes e farmacologia. Analisamos também os dados dos potenciais efeitos adversos que impedem seu uso em animais. Antecedentes apoiam a um alto potencial da eficácia como anti-helmíntico para se três espécies de plantas que crescem na região de Coquimbo: Allium sativum L., Artemisia absinthium L. e Chenopodium ambrosioides L. Os possíveis efeitos secundários do consumo de plantas medicinais ou seus derivados devem ser avaliadas em testes de campo antes de serem utilizados nas em escala produtiva.


ABSTRACT The aim of this study was to determine the potential of the plants which grow at the Coquimbo region in the control of gastrointestinal nematodes in goats. We used a non-experimental approach to evaluate the potential efficacy of medicinal plants as anthelmintics. This research was conducted with exhaustive bibliography referred to the medicinal use of plants in the international literature. We determined the potential of effectiveness of the plants, the consistency of the information about the traditional use, the present compounds and the pharmacology. We also performed an analysis about the potential adverse effects of the plants" application in animals. The collected data support the efficacy of these three species of plants growing at the Coquimbo region as efficient anthelmintic ones: the Allium sativum L., the Artemisia absinthium L. and the Chenopodium ambrosioides L. The possible side effects of the consumption of medicinal plants or their derivatives must be evaluated in field trials before they start being used in a productive scale.


Assuntos
Animais , Feminino , Plantas Medicinais/metabolismo , Ruminantes/classificação , Nematoides/patogenicidade , Parasitos/classificação , Anti-Helmínticos/análise
15.
Dig Dis Sci ; 58(10): 2949-54, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23828140

RESUMO

BACKGROUND: Pyoderma gangrenosum is a serious cutaneous complication seen in approximately 1 % of patients with inflammatory bowel disease (IBD). Oral corticosteroids are the mainstay treatment, although the evidence supporting their use is weak. AIMS: The purpose of this study was to investigate the characteristics of pyoderma gangrenosum associated with Crohn's disease or ulcerative colitis and which treatments are prescribed in Spanish clinical practice. METHODS: In this retrospective, observational study, the medical records from all patients with IBD and a diagnosis of pyoderma gangrenosum attended by the gastroenterology departments of 12 Spanish hospitals were reviewed. Data on patient demographics and characteristics, underlying IBD and treatment, and pyoderma gangrenosum characteristics, treatment, and outcome were collected and analyzed. RESULTS: The data from 67 patients were analyzed (41 [61.2 %] women, 41 [61.2 %] with Crohn's disease, 25 [37.3 %] with ulcerative colitis, and 1 [1.5 %] with indeterminate disease). The underlying disease was in remission in approximately one-third of patients at the time of presentation of pyoderma gangrenosum. Healing was achieved in all patients (in 3 without any systemic therapy). Oral corticosteroids were taken by 51 patients (76.1 %), almost always as first-line treatment, although definitive healing was attained in 19 (28.4 %). Biologic agents such as infliximab and adalimumab were taken by 31 patients (46.3 %) at some point (first-line in 6 patients [9.0 %]), with definitive healing in 29 patients (93.5 %). CONCLUSIONS: Oral corticosteroid therapy remains the most common treatment for pyoderma gangrenosum associated with inflammatory bowel disease. Biologic therapies such as infliximab and adalimumab should also be considered.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Inflamatórias Intestinais/complicações , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/patologia , Adalimumab , Administração Oral , Administração Tópica , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Pioderma Gangrenoso/etiologia , Estudos Retrospectivos , Espanha , Resultado do Tratamento
16.
Arch Soc Esp Oftalmol ; 87(12): 392-5, 2012 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-23121699

RESUMO

OBJECTIVE: To determine the prevalence of diabetic retinopathy (DR) and evaluate our experience in DR screening in a study carried out between the Ophthalmology Department of the University General Hospital of Alicante and Department 19 Primary Care of Alicante by using a non-retinal mydriatic camera and telemedicine. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted on 2,435 diabetic patients from 1 February 2006 to 1 February 2009. Three 45° retinographies of both eyes of each patient were obtained and sent to the Department of Ophthalmology via the hospital intranet. These were then evaluated by 2 ophthalmologists, experts in the retina, with each issuing an individualized report for each patient. RESULTS: The prevalence of DR was 17.90%, with 80.73% of them having mild-moderate proliferative DR, 12.16% severe non-proliferative DR, 2.29% proliferative DR, and 4.82% with diabetic maculopathy associated with any level of retinopathy. The retinographies were considered low quality in 41 patients (1.69%). CONCLUSIONS: We highlight the benefits of the tele-ophthalmology in screening diabetic patients to enable early diagnosis and treatment, and improving the circuit of communication between primary and specialist care.


Assuntos
Redes de Comunicação de Computadores , Retinopatia Diabética/diagnóstico , Telemedicina/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos Transversais , Retinopatia Diabética/epidemiologia , Diagnóstico Precoce , Fundo de Olho , Hospitais Gerais/organização & administração , Hospitais Universitários/organização & administração , Humanos , Lactente , Edema Macular/diagnóstico , Edema Macular/epidemiologia , Edema Macular/etiologia , Programas de Rastreamento , Pessoa de Meia-Idade , Oftalmoscopia , Fotografação/métodos , Prevalência , Espanha/epidemiologia , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/epidemiologia , Vitreorretinopatia Proliferativa/etiologia , Listas de Espera , Carga de Trabalho
17.
Radiologia ; 54 Suppl 1: 38-49, 2012 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-22981140

RESUMO

The greater temporal resolution provided in ultrafast dynamic contrast-enhanced magnetic resonance imaging sequences makes it possible to know the physiological phenomenon of the distribution of the contrast material through a time-signal intensity curve. Analyzing these curves enables us to deduce information relevant to the vascularization and perfusion of tissues, capillary permeability, and the interstitial space in the tumor. A steep curve with early washout in a space-occupying lesion greatly increases the possibility of histological malignancy, although this type of curve is not rare in benign lesions and relatively flat curves are not rare in malignant tumors. Nevertheless, dynamic studies of the uptake of contrast material provide important information for the characterization of neoplasms that, together with the usual signs, can help to differentiate between benign and malignant tumors of adipocyte, chondroid, or neural lineage, clearing up diagnostic uncertainty in certain benign lesions such as osteoid osteoma and ischemic musculoskeletal disease. Furthermore, it enables the accurate determination of the response to chemotherapy, detecting recurrence within the treated tumor early, delimiting more precisely the margins between the tumor and peritumoral edema, and helping in diagnostic planning by determining the most vascularized areas of the tumor, which are more likely to be malignant.


Assuntos
Neoplasias Ósseas/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Musculares/diagnóstico , Humanos , Imageamento por Ressonância Magnética/métodos
19.
Intern Med J ; 42(4): 395-401, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20561097

RESUMO

BACKGROUND/AIM: Acute non-specific abdominal pain (NSAP) is prevalent in 6-25% of the general population and is a common cause of admission to the emergency department (ED). Despite involvement of substantial financial and human resources, there are few data on long-term outcome after initial diagnosis. The aim of this study was to evaluate long-term outcome of patients initially admitted with NSAP to an ED. METHODS: The study involves a 5-year follow-up analysis of prospectively collected data on 104 patients admitted to our ED in 2003 with NSAP. Primary end-point was clinical outcome 5 years after initial ED admission. Predictive risk factors were assessed using a multivariate regression model. RESULTS: 29 patients (28%) had recurring NSAP 5 years after initial ED admission, 76% of these patients received (multiple) diagnostic examinations and 13% eventually required diagnostic (or therapeutic) surgery. Although approximately half of patients with recurring NSAP eventually received a definite diagnosis, 30% still suffered from recurrent abdominal pain. Using regression analysis, no single factor in our dataset could be identified as a predictor for NSAP persistence. CONCLUSION: The long-term impact for patients initially admitted to our ED with acute NSAP is significant--28% of patients continue to suffer from recurring NSAP after 5 years. NSAP therefore remains, despite more advanced diagnostic tools, a true and, as yet, unsolved problem.


Assuntos
Dor Abdominal/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Dor Abdominal/etiologia , Dor Abdominal/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Adulto Jovem
20.
Transgenic Res ; 21(4): 843-53, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22180015

RESUMO

Ubiquitous activation of polyamine catabolism has been demonstrated to have protective effects in mice on fat accumulation and insulin sensitivity/glucose tolerance in, both, normal conditions and after a high fat diet. We have analyzed the endocrine pancreas functionality in four months-old male mice overexpressing the rate limiting enzyme in the polyamine catabolism, spermidine/spermine N¹-acetyltransferase (SSAT). The pancreatic SSAT activity was 37-fold elevated in the transgenic mice, which reduced the total pancreatic and islet pools of spermidine (71%) and spermine (69%), and increased putrescine and N¹-acetyl spermidine. Reduction in the islet ATP levels (65%) was accompanied with increased transcription of 5'-AMP-activated protein kinase (AMPK) (1.5-fold) and Foxa2 (2.7-fold), and reduced HNF4α (67%) and HNF1α (92%), insulin 1 (47%), insulin 2 (50%), and Glut2 (57%). Moreover, the SSAT transgenic mice also presented increased beta cell area, decreased insulin production, and altered glucose-stimulated insulin secretion. It has been hypothesized that the acute activation of the polyamine catabolism produces a futile cycle that greatly decreases the energy reserves of the cell. The lower energy status would activate the energy expenditure regulator, AMPK, which would consequently repress the PI3K/Akt pathway, and activate the transcription factor Foxa2.


Assuntos
Acetiltransferases/genética , Células Secretoras de Insulina/metabolismo , Insulina , Camundongos Transgênicos/metabolismo , Poliaminas/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Glucose/farmacologia , Fator 3-beta Nuclear de Hepatócito/metabolismo , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Camundongos
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