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1.
Breast Cancer Res Treat ; 206(2): 317-328, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38561577

RESUMO

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.


Assuntos
Neoplasias da Mama , Piperazinas , Piridinas , Receptor ErbB-2 , Humanos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Feminino , Piperazinas/uso terapêutico , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Idoso , Adulto , Masculino , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Idoso de 80 Anos ou mais , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Intervalo Livre de Progressão
2.
bioRxiv ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37577676

RESUMO

Spatial cognition research requires behavioral paradigms that can distinguish between different navigational elements, such as allocentric (map-like) navigation and egocentric (e.g., body centered) navigation. To fill this need, we developed a flexible experimental platform that can be quickly modified without the need for significant changes to software and hardware. In this paper, we present this inexpensive and flexible behavioral platform paired with software which we are making freely available. Our behavioral platform serves as the foundation for a range of experiments, and though developed for assessing spatial cognition, it also has applications in the non-spatial domain of behavioral testing. There are two components of the software platform, 'Maze' and 'Stim Trigger'. Both programs can work in conjunction with electrophysiology acquisition systems, allowing for precise time stamping of neural events with behavior. The Maze program includes functionality for automatic reward delivery based on user defined zones. 'Stim Trigger' permits control of brain stimulation via any equipment that can be paired with an Arduino board. We seek to share our software and leverage the potential by expanding functionality in the future to meet the needs of a larger community of researchers.

3.
Rev Neurol ; 75(5): 103-108, 2022 09 01.
Artigo em Espanhol | MEDLINE | ID: mdl-35880963

RESUMO

INTRODUCTION: Pompe disease (PD) is a rare metabolic myopathy with an ample and heterogeneous clinical spectrum, particularly late onset PD (LOPD), which is characterized by appearance at older age and slower disease progression, leading to diagnostic confirmation difficulty and delay. AIM: To describe the genotype and clinical characteristics of Mexican patients with LOPD. MATERIAL AND METHODS: Clinical information from 19 Mexican patients with LOPD confirmed with enzyme activity and GAA gene analysis was reviewed. Genetic information of our population was crossed with international genetic databases. RESULTS: Median age between onset of symptoms and diagnosis was 19 years (range 2-43) and diagnostic confirmation 36 years (range 9-52). Most frequently referred symptoms were proximal axial weakness (n = 17; 89.5%), waddling gait (n = 17; 89.5%) and hyperlordosis (n = 7; 36.8%). Sixteen patients (84.2%) were evaluated with electromyography; a myopathic pattern was reported in 11 (57.8%), but only in 5 patients (26%) paraspinal muscle evaluation was included. The most pathogenic mutations in our group were c.-32-13T>G, c.1799G>A and c.1082C>T. CONCLUSIONS: Similar to other international publications, LOPD in Mexico is clinically heterogeneous; patients may delay years before diagnosis is established. Axial and proximal weakness is the most frequent clinical feature; thus, electromyography with paraspinal muscle evaluation is essential. Except for one, the mutations found in our patients have been previously reported in PD genetic databases.


TITLE: Enfermedad de Pompe de inicio tardío: análisis de una casuística de 19 pacientes mexicanos.Introducción. La enfermedad de Pompe es una miopatía metabólica rara con espectro clínico heterogéneo, especialmente la de inicio tardío, cuya sintomatología es de progresión más lenta y representa un gran reto diagnóstico. Objetivo. Describir el genotipo y las características clínicas de pacientes mexicanos con Pompe de inicio tardío (LOPD). Material y métodos. Se incluyó a 19 pacientes mexicanos con LOPD confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se evaluaron datos clínicos y se revisaron las mutaciones en bases de datos genómicas. Resultados. La mediana de edad de inicio de los síntomas fue de 19 años (rango: 2-43 años), y la edad de diagnóstico, de 36 años (rango: 9-52 años). Los síntomas más frecuentes fueron debilidad axial y proximal (n = 17; 89,5%), marcha basculante (n = 17; 89,5%) e hiperlordosis (n = 7; 36,8%). A 16 pacientes (84,2%) se les realizó electromiografía; 11 (57,8%) describieron patrón miopático y sólo en cinco pacientes (26%) se incluyó la valoración de los músculos paraespinales. Las variantes patogénicas más frecuentes en nuestra casuística fueron c.-32-13T>G, c.1799G>A y c.1082C>T. Conclusiones. Parecido a lo comunicado en publicaciones internacionales, la LOPD en México es clínicamente heterogénea; los pacientes pueden tardar años en llegar al diagnóstico. La debilidad muscular axial y proximal es el dato clínico más frecuente, por lo que la electromiografía debe incluir valoración de los músculos paraespinales. A excepción de una, las mutaciones encontradas en nuestra serie de casos se encuentran previamente descritas en las bases de datos de enfermedad de Pompe.


Assuntos
Doença de Depósito de Glicogênio Tipo II , Doenças Musculares , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , México/epidemiologia , Mutação , Adulto Jovem , alfa-Glucosidases/genética
4.
Acta Ortop Mex ; 35(2): 226-235, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34731929

RESUMO

INTRODUCTION: Knee dislocation is a rare injury but considered serious clinically since it can be accompanied by vascular and neurological injuries that if they do not have a timely diagnosis and treatment can lead to the loss of the limb. Regarding vascular injury, the optimal diagnostic method for the identification of this type of lesion is of the utmost importance. OBJECTIVE: To present the literature review on the epidemiology, classification and diagnostic approach of knee dislocation with or without associated vascular injury. METHODS: Report of the literature found in databases and analyses based on clinical experience and synthesis of these documents. CONCLUSION: Vascular injury is not an uncommon finding in the context of knee dislocation, with a high risk of complications and even amputation if an early diagnosis is not made, the authors recommend angio-CT to confirm the suspected diagnosis and not delay treatment.


INTRODUCCIÓN: La luxación de rodilla es una lesión poco común, pero considerada grave clínicamente, ya que puede acompañarse de lesiones vasculares y neurológicas que si no tienen un diagnóstico y tratamiento oportuno pueden llegar a la pérdida de la extremidad. Respecto a la lesión vascular es de suma importancia el método diagnóstico óptimo para la identificación de este tipo de lesiones. OBJETIVO: Presentar la revisión bibliográfica sobre la epidemiología, clasificación y aproximación diagnóstica de la luxación de rodilla con o sin lesión vascular asociada. MÉTODOS: Reporte de la literatura encontrada en bases de datos y análisis basados en experiencia clínica y síntesis de estos documentos. CONCLUSIÓN: La lesión vascular no es un hallazgo infrecuente en el contexto de una luxación de rodilla, tiene un riesgo elevado de complicaciones e incluso de amputación si no se realiza un diagnóstico temprano, los autores recomiendan la angio-TAC para confirmar la sospecha diagnóstica y no retrasar el tratamiento.


Assuntos
Luxação do Joelho , Lesões do Sistema Vascular , Amputação Cirúrgica , Humanos , Luxação do Joelho/diagnóstico por imagem , Luxação do Joelho/cirurgia , Lesões do Sistema Vascular/diagnóstico por imagem
5.
Semergen ; 44(8): 530-536, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30340977

RESUMO

INTRODUCTION: Integrated care is a top priority for most of the National Health Services. In this study, an evaluation is made on the professional's beliefs and expectations regarding integration. MATERIAL AND METHODS: Between March and June 2017, Health Professionals from El Bierzo, León, Spain, were invited to complete 2 questionnaires on health integration process, including an online questionnaire on patient care integration (405 and 211 participants, respectively out of the total 1854 professionals). RESULTS: Three out of four professionals pointed at communication as the most important factor to achieve integration. Medical records, Health Care Education and medication reconciliation were the other prioritised factors. Care pathways (98%), nurse navigator (93%) or shared care protocols (92%) were highly recommended. The entire Hospital Service (55%) was the preferred link, with Primary Care versus a single consultant for every Primary Care Centre (29%), or for all the whole area (16%).There were no differences between primary and hospital services in most of the tools assessed. CONCLUSIONS: Communication tools are the cornerstone to achieve a successful integration of the care services according to Health Professionals.


Assuntos
Atitude do Pessoal de Saúde , Prestação Integrada de Cuidados de Saúde/organização & administração , Pessoal de Saúde/organização & administração , Assistência ao Paciente/métodos , Adulto , Comunicação , Feminino , Pesquisas sobre Atenção à Saúde , Pessoal de Saúde/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/organização & administração , Espanha
6.
J Hazard Mater ; 263 Pt 1: 20-7, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23993740

RESUMO

In this work, an alternative to deactivate noxious green tide Tetraselmis suecica in the short-term is proposed by employing Perovskite-like cube-shaped, crystalline CaTiO3 semiconductors functionalized with atomic silver nanoparticles. CaTiO3 was prepared by a microwave-assisted hydrothermal method and then Ag(0)NPs (1 wt% of CaTiO3), were added by the photoreduction method. The XRD results show that crystalline CaTiO3 has an orthorhombic unit cell with a Perovskite-like structure. Images obtained by FESEM and HRTEM microscopies show well-faceted CaTiO3 rectangular prismatic morphology functionalizated with silver nanoparticles ≈ 13.5 nm. XPS and EDS-FESEM has confirmed the composition of CaTiO3 and silver occurring mainly as reduced metal. The UV inactivation of noxious T. suecica with Ag/CaTiO3 nanocomposites formed on bare materials results in complete deactivation of the algae in 12 min. The direct contact between harmful algae and Ag/CaTiO3 nanocomposite is necessary to deactivate the algae and inhibits algae viability.


Assuntos
Anti-Infecciosos/farmacologia , Compostos de Cálcio/efeitos da radiação , Clorófitas/efeitos dos fármacos , Clorófitas/efeitos da radiação , Nanocompostos , Óxidos/efeitos da radiação , Prata/farmacologia , Titânio/efeitos da radiação , Anti-Infecciosos/química , Anti-Infecciosos/efeitos da radiação , Compostos de Cálcio/química , Nanocompostos/química , Nanocompostos/efeitos da radiação , Óxidos/química , Prata/química , Prata/efeitos da radiação , Titânio/química , Raios Ultravioleta
7.
J Clin Endocrinol Metab ; 98(10): 4160-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23884782

RESUMO

CONTEXT: Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. OBJECTIVE: The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. DESIGN: A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. RESULTS: Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. CONCLUSIONS: The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Desamino Arginina Vasopressina , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/metabolismo , Receptores de Vasopressinas/metabolismo , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/cirurgia , Testes de Função Hipofisária , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Prognóstico
9.
Trop Med Int Health ; 12(5): 664-72, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17445134

RESUMO

OBJECTIVE: Effective dengue prevention and Aedes aegypti control is a priority for the Cuban health authorities. To enhance effectiveness, strategies oriented towards a more active involvement of communities in control activities are being tested. This paper presents a sociological perspective on a pilot project conducted in the health area ''26 de Julio'' (La Havana) in 1999-2004. METHODS: Instrumental case study based on an exhaustive content analysis of project documents and on observations of a sociologist. RESULTS: The context and the pilot project are systematically described and an analysis of the evolution of the underlying concept of community participation is provided. The pilot experience was a dynamic process influenced by self-reflection of the research team, feedback from research partners and changes in the epidemiological context (provoked by two dengue outbreaks during the study period). Community participation evolved from being just one component in Aedes aegypti control directed by the health staff into a learning and empowering process for the people. This change in the concept of participation was reflected in different aspects of the pilot project such as the learning and evaluation processes. CONCLUSION: Empirical evidence from 5 years of research in the particular context of Cuba showed that moves towards community-based Aedes aegypti control are feasible. However, in order to be successful, community-based dengue prevention should be a social learning process, implying a transfer of power and responsibilities to local people. Actions undertaken must be oriented towards creating local capabilities, strengthening existing structures and organizations and promoting group work for learning participation from participation itself.


Assuntos
Aedes , Participação da Comunidade/métodos , Dengue/prevenção & controle , Insetos Vetores , Animais , Controle de Doenças Transmissíveis/métodos , Comportamento Cooperativo , Cuba/epidemiologia , Tomada de Decisões Gerenciais , Dengue/epidemiologia , Surtos de Doenças , Programas Governamentais/métodos , Educação em Saúde/métodos , Humanos , Controle de Mosquitos/métodos , Projetos Piloto , Projetos de Pesquisa
10.
J Ethnopharmacol ; 103(2): 194-200, 2006 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-16182483

RESUMO

The bark of Rhizophora mangle, the red mangrove, has been used traditionally in folk medicine of Caribbean countries due to its antiseptic, astringent, haemostatic and antifungal properties. Aqueous extracts are rich in tannins and have been proven experimentally to possess antibacterial, wound healing and antiulcerogenic effects. This work was designed to determine the gastroprotective effect of Rhizophora mangle in a model of diclofenac-induced ulcers in rats and to study the mechanisms involved, using the proton pump inhibitor omeprazole as a comparison. The lyophilized extract was given by oral gavage (125 and 62.5mg/kg) three times at 12h intervals before administering diclofenac 100mg/kg. Pretreatment with the extract resulted in a significant decrease of the ulcerated area (P<0.01). Rhizophora mangle induced a recovery of PGE(2) levels, which had been depleted by diclofenac. No anti-inflammatory effect was observed ex vivo or in vitro. The highest dose of the extract provoked a marked increase in glutathione peroxidase and superoxide dismutase activity, which was comparable to omeprazole. Furthermore, lipid peroxidation levels were inhibited in a dose-dependent manner. These results suggest that the gastroprotective effect of Rhizophora mangle in this experimental model appears through an antioxidant and prostaglandin-dependent way.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/uso terapêutico , Antioxidantes/uso terapêutico , Fitoterapia , Casca de Planta , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/antagonistas & inibidores , Antiulcerosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Diclofenaco/antagonistas & inibidores , Diclofenaco/toxicidade , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Rhizophoraceae , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
11.
Biochem Soc Trans ; 33(Pt 2): 331-4, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15787599

RESUMO

Proteolytic enzymes play an essential role in different physiological processes, including development, reproduction and host defence, as well as in numerous pathologies, like inflammatory diseases, neurological disorders or cancer. The completion of the human genome sequence allowed us to determine that more than 2% of all human genes are proteases or protease inhibitors, reflecting the importance of proteolysis in human biology. To understand better the complexity of proteases in human and other model organisms, we have used the available genome sequences of different mammalian organisms, including mouse, rat and chimpanzee, to identify and compare their degradomes, the complete set of protease genes in these species. Surprisingly, the rodent protease complement is more complex when compared with that of primates, mainly due to the expansion of protease families implicated in reproduction and host defence. Similarly, most differences between human and chimpanzee proteases are found in genes implicated in the immune system, which might explain some of the differences between both organisms. We have also found several genes implicated in reproduction, nutrition and the immune system, which are functional in rat, mouse or chimpanzee, but have been inactivated by mutations in the human lineage. These findings suggest that pseudogenization of specific protease genes has been a mechanism contributing to the evolution of the human genome. Finally, we found that proteases implicated in human hereditary diseases, and especially in neurodegenerative disorders, are highly conserved among mammals.


Assuntos
Endopeptidases/genética , Endopeptidases/metabolismo , Genômica , Animais , Humanos , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/genética , Inibidores de Proteases/farmacologia
12.
Cir Pediatr ; 16(1): 44-7, 2003 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-12793295

RESUMO

Biliary atresia is the most common indication for liver transplantation in the pediatric age group. The Kasai portoenterostomy has become established as the primary treatment for biliary atresia. If portoenterostomy fails, death before 2 years of age is likely without liver transplantation. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, which forms a constellation of defects of body symmetry, splenic development and vascular anomalies, including situs inversus, polysplenia and others. The situs inversus was formerly considered an absolute contraindication for liver transplantation. Recently however, several case reports have been published suggesting that neither situs inversus nor this particular subset of vascular abnormalities should be considered contraindications to liver transplantation. We present one case of liver transplantation performed in patient with biliary atresia, situs inversus and polysplenia. This is the first report described in Spain for a liver transplant in a child with biliary atresia plus situs inversus.


Assuntos
Anormalidades Múltiplas/cirurgia , Atresia Biliar/cirurgia , Transplante de Fígado/métodos , Situs Inversus/cirurgia , Baço/anormalidades , Atresia Biliar/complicações , Humanos , Lactente , Masculino , Situs Inversus/complicações , Espanha , Síndrome , Resultado do Tratamento
13.
Arq. bras. med. vet. zootec ; 54(4): 405-413, jul.-ago. 2002. tab, graf
Artigo em Português | LILACS | ID: lil-328417

RESUMO

Este trabalho teve por objetivo avaliar o efeito dos níveis 40, 55 e 70 por cento de concentrado associados a um volumoso de baixa qualidade sobre o consumo e ganho de peso de 16 novilhos mestiços, castrados, com 10 meses de idade e peso vivo inicial médio de 312kg, em delineamento inteiramente ao acaso, com três repetiçöes, durante 63 dias. O volumoso usado foi a aveia (Avena strigosa), tratada com uréia e o concentrado era constituído de milho, farelo de arroz, farelo de soja e minerais. Todas as dietas foram ajustadas para conter 12 por cento de proteína bruta. Houve resposta positiva e linear à proporçäo de concentrado na dieta, para as variáveis ganho de peso diário e consumo de matéria seca expresso em kg/animal/dia, em percentagem do peso vivo e em g por kg de peso metabólico em funçäo da proporçäo de concentrado na dieta. Houve resposta linear negativa para conversäo alimentar. O consumo de matéria seca e o ganho de peso diário aumentaram na medida em que se elevou a proporçäo de concentrado na dieta. O volumoso de baixa qualidade empregado possivelmente limitou o consumo e conseqüentemente o aporte de nutrientes


Assuntos
Animais , Ração Animal , Avena , Bovinos
14.
J Biol Chem ; 276(37): 35008-13, 2001 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-11425849

RESUMO

Zn-alpha(2)-glycoprotein (ZAG) is a member of the major histocompatibility complex (MHC) class I family of proteins and is identical in amino acid sequence to a tumor-derived lipid-mobilizing factor associated with cachexia in cancer patients. ZAG is present in plasma and other body fluids, and its natural function, like leptin's, probably lies in lipid store homeostasis. X-ray crystallography has revealed an open groove between the helices of ZAG's alpha(1) and alpha(2) domains, containing an unidentified small ligand in a position similar to that of peptides in MHC proteins (Sanchez, L. M., Chirino, A. J., and Bjorkman, P. J. (1999) Science 283, 1914-1919). Here we show, using serum-derived and bacterial recombinant protein, that ZAG binds the fluorophore-tagged fatty acid 11-(dansylamino)undecanoic acid (DAUDA) and, by competition, natural fatty acids such as arachidonic, linolenic, eicosapentaenoic, and docosahexaenoic acids. Other MHC class I-related proteins (FcRn, HFE, HLA-Cw*0702) showed no such evidence of binding. Fluorescence and isothermal calorimetry analysis showed that ZAG binds DAUDA with K(d) in the micromolar range, and differential scanning calorimetry showed that ligand binding increases the thermal stability of the protein. Addition of fatty acids to ZAG alters its intrinsic (tryptophan) fluorescence emission spectrum, providing a strong indication that ligand binds in the expected position close to a cluster of exposed tryptophan side chains in the groove. This study therefore shows that ZAG binds small hydrophobic ligands, that the natural ligand may be a polyunsaturated fatty acid, and provides a fluorescence-based method for investigating ZAG-ligand interactions.


Assuntos
Glicoproteínas/metabolismo , Proteínas de Plasma Seminal , Sítios de Ligação , Varredura Diferencial de Calorimetria , Ácidos Graxos/metabolismo , Fluorescência , Glicoproteínas/química , Humanos , Ligantes , Glicoproteína Zn-alfa-2
15.
Vet Hum Toxicol ; 43(3): 156-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11383656

RESUMO

We studied the toxicity caused by chronic ingestion of Pteridium aquilinum (bracken) in cattle in the humid Chaco of Tarija, Bolivia. Bovine enzootic haematuria (BEH) and Carcinoma of the esophagus (CE) affected the herds. Sick animals showed caquexia, anemia, leucopenia and urine that turned from pink to intense red color with the presence of blood clots. Cattle grazed in the humid forests of the mountains where P aquilinum represented more than 50% of the plants. P aquilinum var arachnoideum and P aquilinum var Caudatum were present. Toxic norsesquiterpene, ptaquiloside, was identified in both varieties. Carcinomas were in the urinary bladders and esophagus of 100% and 50% of the cattle, respectively. Control of the intoxication could be difficult due to geographic characteristics of this Bolivian region.


Assuntos
Doenças dos Bovinos/etiologia , Neoplasias Esofágicas/veterinária , Hematúria/veterinária , Intoxicação por Plantas/veterinária , Plantas Tóxicas/intoxicação , Animais , Bolívia/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Clima , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Hematúria/epidemiologia , Hematúria/etiologia , Intoxicação por Plantas/complicações , Intoxicação por Plantas/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/veterinária
16.
Clin Cancer Res ; 7(4): 846-53, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11309332

RESUMO

Zinc alpha-2-glycoprotein (ZAG) is a M(r) 41,000 glycoprotein secreted by a variety of normal epithelia. ZAG was recently shown to stimulate lipolysis in adipocytes, leading to the development of cachexia in animals with ZAG-producing tumors. To understand the possible contribution of ZAG to the development of cachexia in men with prostate cancer, ZAG production by normal and malignant prostate tissue was investigated using immunohistochemical assays. Anti-ZAG monoclonal antibodies reacted strongly with normal prostate epithelium but not with other components of prostate or seminal vesicles. The majority of prostate cancers tested (35 of 48; 73%) also reacted with anti-ZAG antibodies. High-grade tumors expressed significantly less ZAG than moderate-grade tumors (mean ZAG score 1.1 versus 1.9; P < 0.01). Men with ZAG-producing prostate carcinomas had elevated levels of serum ZAG relative to their normal age- and race-matched controls (P < 0.02). Furthermore, s.c. growth of human ZAG-producing murine tumors in syngeneic mice and orthotopic growth of ZAG-producing human prostate carcinomas in nude rats resulted in readily detectable levels of human ZAG in the serum. Taken together, these studies show that ZAG production by prostate cancer can lead to systemically elevated serum ZAG levels that may be useful diagnostically. The effects of elevated systemic ZAG on cachexia-associated complications in patients with advanced prostate cancer deserves additional investigation.


Assuntos
Biomarcadores Tumorais/biossíntese , Glicoproteínas/biossíntese , Neoplasias da Próstata/metabolismo , Proteínas de Plasma Seminal , Idoso , Animais , Anticorpos Monoclonais/imunologia , Biomarcadores Tumorais/sangue , Caquexia/metabolismo , Modelos Animais de Doenças , Epitélio/metabolismo , Feminino , Glicoproteínas/sangue , Glicoproteínas/imunologia , Glicoproteínas/metabolismo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Glândulas Seminais/metabolismo , Glicoproteína Zn-alfa-2
17.
Plant Cell Physiol ; 42(1): 54-62, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11158444

RESUMO

The isoform composition of the 14.4 kDa profilin polypeptide was analyzed in seeds, leaves, flowers, roots and root-nodules from Phaseolus vulgaris L. Isoforms of pIs approximately 4.4-5 were present in all the tissues analyzed. The biochemical features of the protein present in seed tissue were determined. Seed profilin bound to Phenyl-Sepharose under low salt conditions which suggested a hydrophobic interaction; however, it was not associated with microsomal membranes nor it partitioned as a hydrophobic protein in Triton X-114. Fractions eluting from poly-L-proline or Phenyl-Sepharose columns contained well detectable amounts of profilin but no actin, suggesting that most of the protein was not present as profilactin in the seed. However, seed profilin appeared to be in some kind of complex since several molecular weight species were observed on native gels. In addition, profilin was found preferentially in the embryo axis and light microscopic immunolocalization showed a cytoplasmic distribution in this tissue.


Assuntos
Proteínas Contráteis , Fabaceae/química , Proteínas dos Microfilamentos/química , Proteínas de Plantas/química , Plantas Medicinais , Sementes/química , Western Blotting , Cromatografia em Agarose , Citoplasma/metabolismo , Eletroforese , Fabaceae/metabolismo , Técnicas In Vitro , Proteínas dos Microfilamentos/análise , Proteínas dos Microfilamentos/metabolismo , Microscopia Eletrônica , Microssomos/metabolismo , Folhas de Planta/química , Proteínas de Plantas/análise , Proteínas de Plantas/metabolismo , Raízes de Plantas/química , Profilinas , Isoformas de Proteínas/análise , Isoformas de Proteínas/química , Sementes/metabolismo , Sementes/ultraestrutura
18.
J Biol Chem ; 276(13): 10253-62, 2001 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-11113146

RESUMO

Remodeling of fibrillar collagen in mouse tissues has been widely attributed to the activity of collagenase-3 (matrix metalloproteinase-13 (MMP-13)), the main collagenase identified in this species. This proposal has been largely based on the repeatedly unproductive attempts to detect the presence in murine tissues of interstitial collagenase (MMP-1), a major collagenase in many species, including humans. In this work, we have performed an extensive screening of murine genomic and cDNA libraries using as probe the full-length cDNA for human MMP-1. We report the identification of two novel members of the MMP gene family which are contained within the cluster of MMP genes located at murine chromosome 9. The isolated cDNAs contain open reading frames of 464 and 463 amino acids and are 82% identical, displaying all structural features characteristic of archetypal MMPs. Comparison for sequence similarities revealed that the highest percentage of identities was found with human interstitial collagenase (MMP-1). The new proteins were tentatively called Mcol-A and Mcol-B (Murine collagenase-like A and B). Analysis of the enzymatic activity of the recombinant proteins revealed that both are catalytically autoactivable but only Mcol-A is able to degrade synthetic peptides and type I and II fibrillar collagen. Both Mcol-A and Mcol-B genes are located in the A1-A2 region of mouse chromosome 9, Mcol-A occupying a position syntenic to the human MMP-1 locus at 11q22. Analysis of the expression of these novel MMPs in murine tissues revealed their predominant presence during mouse embryogenesis, particularly in mouse trophoblast giant cells. According to their structural and functional characteristics, we propose that at least one of these novel members of the MMP family, Mcol-A, may play roles as interstitial collagenase in murine tissues and could represent a true orthologue of human MMP-1.


Assuntos
Colagenases/química , Implantação do Embrião , Embrião de Mamíferos/enzimologia , Metaloproteinase 1 da Matriz/química , Metaloproteinases da Matriz/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Mapeamento Cromossômico , Clonagem Molecular , Colágeno/metabolismo , Colagenases/genética , DNA Complementar/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Biblioteca Gênica , Vetores Genéticos , Humanos , Hibridização in Situ Fluorescente , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinases da Matriz/genética , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Família Multigênica , Fases de Leitura Aberta , Filogenia , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Útero/enzimologia , Útero/metabolismo
20.
Rev Latinoam Microbiol ; 42(1): 13-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10948824

RESUMO

A 5-year retrospective study (1992-1996) to look at the situation of human tuberculosis was conducted in Querétaro, México. Also, a 6-month study to determine the frequency of gross lesions in dairy cattle at slaughter, and a short experiment to evaluate the effect of sodium borate in the survival of M. bovis in lesions were carried out. The number of cases were 114 in 1992, 211 in 1995, and 174 in 1996. Possible risk factors were: overcrowding, under-nutrition, previous cases of TB in the family, concurrent Diabetes mellitus, poor personal hygiene, smoking, and alcohol abuse. Eighty percent of the cases were pulmonary. The number of cases increase with age, from 5% in patients 10-year old or younger to 42% in patients 50-year old or older. Seventy-two percent were cured, and only 6% die. Persistent coughing was by far the most observed clinical symptom. From 112 acid-fast negative samples, 8.9% were positive by culture. From 1,201 carcasses revised at slaughter, 17% presented TB-gross lesions. Ninety-six percent were localized lesions involving frequently a single organ, mostly retropharyngeal, mediastinal, mesenteric and mandibular lymph. From 102 lesions, 95% were TB-compatible, and 79% were positive to isolation of M. bovis. Most affected animals were female > 2 years old. It was observed that keeping lesions in a 6% sodium borate solution does not affect the diagnosis of M. bovis by culture after 150 days.


Assuntos
Tuberculose Bovina/epidemiologia , Tuberculose/epidemiologia , Matadouros , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Idoso , Animais , Boratos/farmacologia , Bovinos , Criança , Pré-Escolar , Comorbidade , Meios de Cultura , Feminino , Habitação , Humanos , Higiene , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium bovis/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Preservação Biológica/métodos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estações do Ano , Soluções/farmacologia , Manejo de Espécimes/métodos , Tuberculose/microbiologia , Tuberculose Bovina/microbiologia
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