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1.
BMC Health Serv Res ; 24(1): 404, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553723

RESUMO

BACKGROUND: Colorectal cancer (CRC) continues to be a major cause of death in the U.S. despite the availability of effective screening tools. U.S. Latinos have lower rates of CRC screening and higher rates of death due to colorectal disease compared to non-Hispanic whites. Federally Qualified Health Centers (FQHCs) serve medically underserved populations, including many Latino patients. Given the low CRC screening rates, identifying culturally sensitive and cost-effective methods of promoting screening is a priority for many FQHCs. METHODS: We interviewed FQHC leaders and providers using the Consolidated Framework for Implementation Research (CFIR) to identify barriers and facilitators to implementation of a multilevel, multicomponent (ML-MC) CRC screening intervention (i.e., promotor navigation and group-based education) in FQHCs. A rapid qualitative analysis approach was used to identify themes organized according to the following CFIR constructs: intervention characteristics, outer and inner settings, and characteristics of the individual. RESULTS: We completed interviews with 13 healthcare professionals in leadership positions at six FQHCs. The participating FQHCs perceived the ML-MC screening CRC program as feasible and expressed interest in implementing the program at their sites. Facilitators included financial incentives for increasing screening rates, the need for patient education programming, and involving promotores to support the work of clinical teams. Barriers included concerns about available resources to implement new programs, lack of federal reimbursement for health education, competing priorities of other health concerns, and the need for more resources for confirmatory screening and treatment following a positive screen. CONCLUSIONS: FQHCs provide essential primary care to millions of underserved patients in the U.S. and have the ability and motivation to provide screenings for colorectal cancer. Partnering with an academic institution to deliver a group-based, promotor-led CRC screening intervention for patients not up to date with screening could help increase screening rates. By identifying the specific barriers and facilitators to implementing CRC intervention, findings suggest that group-based, promotor-led interventions are a promising approach.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Atenção à Saúde , Hispânico ou Latino , Pessoal de Saúde , Programas de Rastreamento
2.
Mol Genet Genomics ; 298(2): 455-472, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36604348

RESUMO

The PumAB type-II toxin-antitoxin (TA) system is encoded by pumAB genes that are organized into an operon. This system is encoded by the pUM505 plasmid, isolated from a Pseudomonas aeruginosa clinical strain. The pumA gene encodes a putative RelE toxin protein (toxic component), whereas the pumB gene encodes a putative HTH antitoxin protein. The expression of the PumAB system in Escherichia coli confers plasmid stability. In addition, PumA toxin overexpression in P. aeruginosa possesses the capability to increase bacterial virulence, an effect that is neutralized by the PumB antitoxin. The aim of this study was to establish the mechanism of regulation of the PumAB toxin-antitoxin system from pUM505. By an in silico analysis of the putative regulatory elements, we identified two putative internal promoters, PpumB and PpumB-AlgU (in addition to the already reported PpumAB), located upstream of pumB. By RT-qPCR assays, we determined that the pumAB genes are transcribed differentially, in that the mRNA of pumB is more abundant than the pumA transcript. We also observed that pumB could be expressed individually and that its mRNA levels decreased under oxidative stress, during individual expression as well as co-expression of pumAB. However, under stressful conditions, the pumA mRNA levels were not affected. This suggests the negative regulation of pumB by stressful conditions. The PumB purified protein was found to bind to a DNA region located between the PpumAB and the pumA coding region, and PumA participates in PumB binding, suggesting that a PumA-PumB complex co-regulates the transcription of the pumAB operon. Interestingly, the pumA mRNA levels decreased after incubation in vitro with PumB protein. This effect was repressed by ribonuclease inhibitors, suggesting that PumB could function as an RNAse toward the mRNA of the toxin. Taken together, we conclude that the PumAB TA system possesses multiple mechanisms to regulate its expression, as well as that the PumB antitoxin generates a decrease in the mRNA toxin levels, suggesting an RNase function. Our analysis provides new insights into the understanding of the control of TA systems from mobile plasmid-encoded genes from a human pathogen.


Assuntos
Antitoxinas , Toxinas Bacterianas , Sistemas Toxina-Antitoxina , Humanos , Antitoxinas/genética , Antitoxinas/metabolismo , Toxinas Bacterianas/genética , Sistemas Toxina-Antitoxina/genética , Proteínas Reguladoras de Apoptose/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , RNA Mensageiro , Ribonucleases/genética , Ribonucleases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica
3.
Opt Express ; 31(3): 3504-3519, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785342

RESUMO

Nowadays, atom-based quantum sensors are leaving the laboratory towards field applications requiring compact and robust laser systems. Here we describe the realization of a compact laser system for atomic gravimetry. Starting with a single diode laser operating at 780 nm and adding only one fiber electro-optical modulator, one acousto-optical modulator and one laser amplifier we produce laser beams at all the frequencies required for a Rb-87 atomic gravimeter. Furthermore, we demonstrate that an atomic fountain configuration can also be implemented with our laser system. The modulated system reported here represents a substantial advance in the simplification of the laser source for transportable atom-based quantum sensors that can be adapted to other sensors such as atomic clocks, accelerometers, gyroscopes or magnetometers with minor modifications.

4.
Appl Opt ; 62(24): 6518-6527, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706846

RESUMO

Optical magnetometers based on electromagnetically induced transparency (EIT) in atomic vapor can in principle achieve outstanding sensitivity and accuracy in a small volume. Up until now, however, the predicted fundamental quantum-noise-limited sensitivity has not been achieved in practice due to various technical limitations associated with the measurement apparatus. Here we analyze these restrictions and propose viable mitigation strategies for performance optimization. As an example, we show that an EIT magnetometer can theoretically achieve sensitivity better than 100 fT at 1 s measurement time under realistic conditions.

5.
Rev Med Chil ; 151(11): 1427-1436, 2023 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-39270109

RESUMO

Patients placed in a prone position due to COVID-19 present a more severe disease, longer stay in ICU and have more significant complications associated with positioning than other patients. AIM: To identify social, health, and hospital factors associated with mortality and functional recovery in activities of daily living (ADL) in patients admitted to the ICU due to COVID-19 who were in the prone position. METHODS: We conducted a prospective observational study between June 2021 and March 2022 at the San José Clinical Hospital. The study included people 18 years of age or older admitted to the ICU due to COVID-19 who were in the prone position. Using logistic regression, we searched for factors associated with the risk of in-hospital mortality. Using linear regression, we also analyzed factors associated with functional recovery in ADL at discharge and post-discharge. RESULTS: In 85 patients included, being men, older age, history of mental health, cardiorespiratory disease, and living in a commune of high social priority were associated with a higher risk of in-hospital mortality. A greater number of days of hospitalization was associated with less functional recovery at discharge and post-discharge. In contrast, more cycles in prone position during hospitalization and higher education level were associated with greater post-discharge functional recovery. CONCLUSIONS: The survival and functional prognosis of patients with severe COVID-19 can be predicted early through a biopsychosocial evaluation of their characteristics. Intrahospital actions could improve functional recovery in ADL in the short term in critically ill patients surviving COVID-19.


Assuntos
Atividades Cotidianas , COVID-19 , Mortalidade Hospitalar , Recuperação de Função Fisiológica , Humanos , COVID-19/mortalidade , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Decúbito Ventral , Unidades de Terapia Intensiva/estatística & dados numéricos , Fatores de Risco , SARS-CoV-2 , Posicionamento do Paciente/métodos , Adulto , Tempo de Internação/estatística & dados numéricos
6.
Reumatismo ; 75(1)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154252

RESUMO

Cutaneous lupus erythematosus (CLE) is classified into three groups - acute, subacute, and chronic - based on clinical and histopathological characteristics. The risk of systemic manifestations varies among these groups. There are few studies on CLE epidemiology. For this reason, this paper aims to describe CLE prevalence and demographics in Colombia between 2015 and 2019. This descriptive, cross-sectional study used the international classification of diseases, tenth revision, for CLE subtypes, utilizing official data from the Colombian Ministry of Health. In people older than 19 years, 26,356 CLE cases were registered, yielding a prevalence of 76 cases per 100,000 population. CLE was more frequent in females, at a 5:1 ratio compared to males. The most common clinical presentation was discoid lupus erythematosus, in 45% of cases. The majority of cases occurred in people between 55 and 59 years old. This is the first study that describes CLE demographics in adults in Colombia. Findings regarding clinical subtypes and female predominance are consistent with those in the medical literature.


Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Colômbia/epidemiologia , Estudos Transversais , Lúpus Eritematoso Cutâneo/epidemiologia , Prevalência
7.
Helminthologia ; 59(1): 104-110, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35601766

RESUMO

We describe for the first time the transmission route employed by the parasitic larvae of the freshwater mussel Anodontites trapesialis (Lamarck, 1819) during cohabitation on the guppy Poecilia reticulata Peter, 1859. The freshwater mussel and fish-host were employed as a model system to investigate the infection and parasite establishment. Laboratory experiments included video recording and histopathological analysis of the infection. In vivo video observations demonstrated that lasidium larvae could be transmitted to guppies during direct contact. A series of histology samples and photography suggest that this larva attaches and colonizes possibly on-site on the outer surface of the fish, causing cellular inflammation in the epidermis layer with cellular hyperplasia in the zone of parasite attachment. An evident hyaline layer, cellular hypertrophy, and a large number of undifferentiated proliferating cells were observed. Hemorrhagic tissue and swelling were observed in the epidermis and dermic zone. The total number of larvae per male and female guppy was 525 ± 86 and 494 ± 167, respectively. No parasitic preference was detected for male versus female parasitized fish.

8.
Helminthologia ; 59(1): 94-103, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35601767

RESUMO

The gray snapper Lutjanus griseus is a commercially important fish species along its distribution range in the western Atlantic Ocean. However, despite its importance, there is still little knowledge about its parasitic fauna for the Mexican coasts of the Gulf of Mexico. The aims of this research were to generate a list of the parasitic fauna present in juvenile gray snapper L. griseus from a coastal lagoon located in southeastern Mexico, to evaluate the infection levels of parasites and to determine the relationship between the abundance of parasites and the fish size and condition factor. Samples of L. griseus (12 - 29.2 mm) were obtained in two periods of the year (dry and rainy seasons) to examine the intra-annual variability of its parasitic fauna. A total of 17 parasite species were recorded belonging to six taxonomic groups (Myxozoa, Monogenea, Digenea, Cestoda, Nematoda and Acanthocephala). The highest levels of infection (abundance, prevalence and intensity of infection) were found for the monogeneans Euryhaliotrema griseus and Euryhaliotrema fastigatum. There were no significant correlations between the total abundance of parasites and the fish condition and size (total length) in not any of the two seasons studied, suggesting that the body size and the biological condition index of the host did not directly influence the abundance of parasites in early life stages of L. griseus. Moreover, the species of parasites found that could be zoonotic for humans through the consumption of raw or inadequately cooked fish were the nematodes Contracaecum sp. type 1, Contracaecum sp. type 2, Cucullanus pargi and Pseudoterranova sp. The presence of the monogeneans E. griseus and E. fastigatum was also highlighted because these ectoparasite species are known to cause harm to fish under culture systems. All the parasite species found in this study, except nematodes, were new records of geographic distribution.

9.
Epidemiol Infect ; 149: e145, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34130765

RESUMO

The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.


Assuntos
COVID-19/complicações , Herpes Simples/etiologia , Herpes Zoster/etiologia , Herpesvirus Humano 3/fisiologia , Simplexvirus/fisiologia , Ativação Viral , Adulto , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Herpes Simples/diagnóstico , Herpes Simples/virologia , Herpes Zoster/diagnóstico , Herpes Zoster/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha/epidemiologia
10.
Alzheimers Dement ; 16(1): 60-70, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914226

RESUMO

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.


Assuntos
Demência Frontotemporal , Predisposição Genética para Doença , Mutação/genética , Testes Neuropsicológicos/estatística & dados numéricos , Fatores Etários , Idoso , Encéfalo/patologia , Proteína C9orf72/genética , Feminino , Demência Frontotemporal/classificação , Demência Frontotemporal/genética , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Progranulinas/genética , Proteínas tau/genética
11.
Helminthologia ; 56(3): 211-218, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31662693

RESUMO

The aim of this investigation was to identify the parasites present in the largely understudied pleasure oyster Crassostrea corteziensis in Sinaloa state in the northwestern Mexican Pacific coast. Inspection of twenty-eight oysters collected on "Ceuta" lagoon revealed the presence of the digenean Stephanostomum sp. (Digenea: Acanthocolpidae) cysts. Metacercariae were found encapsulated and embedded in the digestive gland and mantle tissue of oysters. The prevalence of infection revealed that 84.6 % were infected, the abundance was 13.62, with a mean intensity of 16.09 per host. The members of this genus are characterized by a double crown of spines in the cephalic region surrounding the buccal opening of the worm. Significantly, we report the first incidence of the digenean Stephanostomum sp of the family Acanthocolpidae parasitizing Crassostrea corteziensis. Further we report that this bivalve is now considered a new intermediate host, and the northwestern Mexican Pacific coast is a new geographical distribution area for this digenean. The findings contribute to our understanding of the biology, biodiversity and host preference of these parasites, with implications for health risks posed by human consumption of the pleasure oyster.

12.
J Neurooncol ; 140(1): 107-113, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29959694

RESUMO

PURPOSE: The neuroimaging diagnosis of diffuse gliomas can be challenging owing to their variable clinical and radiologic presentation. The purpose of this study was to identify factors that are associated with imaging errors in the diagnosis of diffuse gliomas. METHODS: A retrospective case-control analysis was undertaken. 18 misdiagnosed diffuse gliomas on initial neuroimaging (cases) and 108 accurately diagnosed diffuse gliomas on initial neuroimaging (controls) were collected. Clinical, pathological, and imaging metrics were tabulated for each patient. The tabulated metrics were compared between cases and controls to determine factors associated with misdiagnosis. RESULTS: Cases of misdiagnosed diffuse glioma (vs controls) were more likely to undergo initial triage as a stroke workup [OR 14.429 (95% CI 4.345, 47.915), p < 0.0001], were less likely to enhance [OR 0.283 (95% CI 0.098, 0.812), p = 0.02], were smaller (mean diameter 4.4 vs 6.0 cm, p = 0.0008), produced less midline shift (median midline shift 0.0 vs 2.0 mm, p = 0.003), were less likely to demonstrate necrosis [OR 0.156 (95% CI 0.034-0.713), p = 0.008], and were less likely to have IV contrast administered on the initial MRI [OR 0.100 (95% CI 0.020, 0.494), p = 0.008]. CONCLUSION: Several clinical and radiologic metrics are associated with diffuse gliomas that are missed or misdiagnosed on the initial neuroimaging study. Knowledge of these associations may aid in avoiding misinterpretation and accurately diagnosing such cases in clinical practice.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Erros de Diagnóstico , Glioma/diagnóstico por imagem , Neuroimagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Erros de Diagnóstico/prevenção & controle , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
13.
Microb Pathog ; 112: 259-268, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28970172

RESUMO

Pseudomonas aeruginosa plasmid pUM505 possesses a pathogenicity island that contains the pumAB genes that encode products with sequence similarity to Toxin-Antitoxin (TA) modules. RT-PCR assays on the overlapping regions of the pumAB genes generated a bicistronic messenger RNA, suggesting that they form an operon. When the pumAB genes were cloned into the pJET vector, recombinant plasmid pJET-pumAB was maintained under nonselective conditions in Escherichia coli cells after six daily subcultures, whereas pJET without pumAB genes was lost. These data indicate that pumAB genes confer post-segregational plasmid stability. In addition, overexpression of the PumA protein in the E. coli BL21 strain resulted in a significant growth inhibition, while BL21 co-expressing the PumA and PumB proteins did not show growth inhibition. These results indicate that pumAB genes encode a TA system where the PumB protein counters the toxic effects of the PumA toxin. Furthermore, P. aeruginosa PAO1 transformants with the pumA gene increased Caenorhabditis elegans and mouse mortality rate and improved mouse organ invasion, effects neutralized by the PumB protein. Moreover, purified recombinant His-PumA protein decreased the viability of C. elegans, indicating that the PumA protein could acts as a toxin. These results indicate that PumA has the potential to promoter the PAO1 virulence against C. elegans and mice when is expressed in absence of PumB. This is the first description, to our knowledge, of a plasmid-encoded TA system that confers plasmid stability and encoded a toxin with the possible ability to increase the P. aeruginosa virulence.


Assuntos
Toxinas Bacterianas/genética , Toxinas Bacterianas/toxicidade , Genes Bacterianos/genética , Plasmídeos/genética , Pseudomonas aeruginosa/genética , Sistemas Toxina-Antitoxina/genética , Fatores de Virulência/genética , Animais , Antitoxinas/genética , Proteínas de Bactérias/genética , Sequência de Bases , Caenorhabditis elegans/efeitos dos fármacos , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óperon/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/patogenicidade , RNA Bacteriano/análise , Proteínas Recombinantes/genética , Análise de Sequência , Virulência/genética
14.
J Cell Biochem ; 117(8): 1926-33, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26756719

RESUMO

Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL-2H3). It exhibits immunomodulatory, anti-inflammatory and anti-apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti-inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL-2H3 were pre-treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12-myristate 13-acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre-treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF-α and IL-6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF-κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down-regulation of mast cell activation. J. Cell. Biochem. 117: 1926-1933, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Mastócitos/imunologia , Melatonina/farmacologia , NF-kappa B/imunologia , Transdução de Sinais/efeitos dos fármacos , Animais , Calcimicina/toxicidade , Linhagem Celular Tumoral , Interleucina-6/imunologia , Ratos , Transdução de Sinais/imunologia , Acetato de Tetradecanoilforbol/toxicidade , Fator de Necrose Tumoral alfa/imunologia
15.
Transfus Apher Sci ; 53(3): 293-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26043812

RESUMO

Platelet units for transfusion purposes are obtained manually from whole blood or by apheresis, in an automated process. In both methods, platelets during storage present a characteristics grouped under the name "storage lesion" that are associated with adverse effects on platelet units. Oxidative stress has been claimed to be one of major causes, leading to activation and apoptosis processes affecting their post transfusion functionality. In this work, we observed an association between apheresis and a reduced presence of oxidative stress and better results in functional markers in stored platelets, compared to manually obtained platelets. Then, apheresis which would ensure a greater number of functional platelets during the 5 days of storage, compared to concentrates obtained from whole blood.


Assuntos
Plaquetas/metabolismo , Preservação de Sangue , Estresse Oxidativo , Ativação Plaquetária , Plaquetoferese , Adulto , Feminino , Humanos , Masculino , Transfusão de Plaquetas , Fatores de Tempo
16.
Clin Endocrinol (Oxf) ; 80(2): 261-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23746264

RESUMO

OBJECTIVE: Twenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data. DESIGN: Observational study (enrolment phase of Phase III study). METHODS: Patients (n = 152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30-145 nmol/24 h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2 weeks. RESULTS: Over 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48-56). The intrapatient CV was 51% (95% CI: 44-58) for samples 1 and 2, 49% (95% CI: 43-56) for samples 3 and 4 and 54% (95% CI: 49-59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism. CONCLUSIONS: There is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity.


Assuntos
Hidrocortisona/urina , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/urina , Somatostatina/análogos & derivados , Adulto , Idoso , Síndrome de Cushing/patologia , Síndrome de Cushing/urina , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/patologia , Recidiva , Valores de Referência , Índice de Gravidade de Doença , Somatostatina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
17.
Pituitary ; 17(4): 320-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23943009

RESUMO

In a previous 15-day, Phase II study of patients with de novo or persistent/recurrent Cushing's disease (core study), treatment with pasireotide 600 µg sc bid reduced urinary free cortisol (UFC) levels in 76% of patients and normalized UFC in 17%. The objective of this study was to evaluate the efficacy and safety of extended treatment with pasireotide. This was a planned, open-ended, single-arm, multicenter extension study (primary endpoint: 6 months). Patients aged ≥18 years with Cushing's disease who completed the core study could enter the extension if they achieved UFC normalization at core study end and/or obtained significant clinical benefit. Of the 38 patients who completed the core study, 19 entered the extension and 18 were included in the efficacy analyses (three responders, 11 reducers, four non-reducers in the core study). At data cut-off, median treatment duration in the extension was 9.7 months (range: 2 months to 4.8 years). At extension month 6, 56% of the 18 patients had lower UFC than at core baseline and 22% had normalized UFC. Of the four patients who remained on study drug at month 24, one had normalized UFC. Reductions in serum cortisol, plasma adrenocorticotropic hormone, body weight and diastolic blood pressure were observed. The most common adverse events were mild-to-moderate gastrointestinal disorders and hyperglycemia. Pasireotide offers a tumor-directed medical therapy that may be effective for the extended treatment of some patients with Cushing's disease.


Assuntos
Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Somatostatina/análogos & derivados , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Somatostatina/uso terapêutico , Adulto Jovem
18.
Biomed Microdevices ; 15(5): 849-58, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23660841

RESUMO

Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.


Assuntos
Epitélio Corneano/química , Pletismografia de Impedância/instrumentação , Animais , Compostos de Benzalcônio/metabolismo , Impedância Elétrica , Eletrodos , Desenho de Equipamento , Olho/efeitos dos fármacos , Olho/metabolismo , Permeabilidade , Coelhos
19.
J Pineal Res ; 55(2): 103-20, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23889107

RESUMO

Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. In recent years, a considerable amount of experimental evidence has accumulated showing a relationship between the nervous, endocrine, and immune systems. The molecular basis of the communication between these systems is the use of a common chemical language. In this framework, currently melatonin is considered one of the members of the neuroendocrine-immunological network. A number of in vivo and in vitro studies have documented that melatonin plays a fundamental role in neuroimmunomodulation. Based on the information published, it is clear that the majority of the present data in the literature relate to lymphocytes; thus, they have been rather thoroughly investigated, and several reviews have been published related to the mechanisms of action and the effects of melatonin on lymphocytes. However, few studies concerning the effects of melatonin on cells belonging to the innate immunity have been reported. Innate immunity provides the early line of defense against microbes and consists of both cellular and biochemical mechanisms. In this review, we have focused on the role of melatonin in the innate immunity. More specifically, we summarize the effects and action mechanisms of melatonin in the different cells that belong to or participate in the innate immunity, such as monocytes-macrophages, dendritic cells, neutrophils, eosinophils, basophils, mast cells, and natural killer cells.


Assuntos
Imunidade Inata , Melatonina/fisiologia , Sistema Fagocitário Mononuclear/imunologia , Animais , Granulócitos/imunologia , Humanos , Células Matadoras Naturais/imunologia , Melatonina/biossíntese , Melatonina/metabolismo
20.
J Pineal Res ; 55(1): 26-30, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23607887

RESUMO

Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin.


Assuntos
Cerveja , Fermentação/fisiologia , Hordeum/metabolismo , Melatonina , Leveduras/metabolismo , Análise de Variância , Melatonina/análise , Melatonina/metabolismo
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