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The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid-liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15-0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis.
Assuntos
Microextração em Fase Líquida , Zolpidem , Zolpidem/sangue , Humanos , Microextração em Fase Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Sonicação/métodos , Reprodutibilidade dos Testes , Hipnóticos e Sedativos/sangue , Limite de Detecção , Piridinas/sangueRESUMO
PURPOSE OF REVIEW: Familial hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that, all people with Familial Hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. RECENT FINDINGS: In the last year, several studies have been published focusing on the contribution of diabetes to Familial Hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. SUMMARY: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.
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Aterosclerose , Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Humanos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Hiperlipoproteinemia Tipo II/epidemiologia , LDL-Colesterol , Aterosclerose/complicações , Aterosclerose/epidemiologia , Aterosclerose/diagnóstico , Fatores de Risco de Doenças CardíacasRESUMO
Metabolic stress causes activation of the cJun NH2-terminal kinase (JNK) signal transduction pathway. It is established that one consequence of JNK activation is the development of insulin resistance and hepatic steatosis through inhibition of the transcription factor PPARα. Indeed, JNK1/2 deficiency in hepatocytes protects against the development of steatosis, suggesting that JNK inhibition represents a possible treatment for this disease. However, the long-term consequences of JNK inhibition have not been evaluated. Here we demonstrate that hepatic JNK controls bile acid production. We found that hepatic JNK deficiency alters cholesterol metabolism and bile acid synthesis, conjugation, and transport, resulting in cholestasis, increased cholangiocyte proliferation, and intrahepatic cholangiocarcinoma. Gene ablation studies confirmed that PPARα mediated these effects of JNK in hepatocytes. This analysis highlights potential consequences of long-term use of JNK inhibitors for the treatment of metabolic syndrome.
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Ácidos e Sais Biliares/metabolismo , Colangiocarcinoma/enzimologia , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Animais , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/fisiopatologia , Homeostase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 8 Ativada por Mitógeno/genética , Proteína Quinase 9 Ativada por Mitógeno/genética , PPAR alfa/genética , PPAR alfa/metabolismoRESUMO
BACKGROUND: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America. METHODS: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact. RESULTS: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care. CONCLUSIONS: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes. LAY SUMMARY: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes.
Assuntos
Oncologia , Neoplasias , Criança , Humanos , América Latina , Hospitais Pediátricos , HospitalizaçãoRESUMO
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.
Assuntos
Biocatálise , Meios de Cultura/química , Ibuprofeno/química , Sorbitol/química , Animais , Esterificação , Hidrólise , Ibuprofeno/síntese química , Lipase/metabolismo , Solventes , Especificidade por Substrato , Suínos , Temperatura , Fatores de Tempo , Água/químicaRESUMO
PURPOSE: Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. METHODS: Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. RESULTS: Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. CONCLUSION: p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.
Assuntos
Diagnóstico por Computador , Doença de Fabry/complicações , Doença de Fabry/genética , Mutação , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Adulto , Idoso , Biomarcadores , Doença de Fabry/fisiopatologia , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Prognóstico , Refração Ocular , Doenças Retinianas/fisiopatologia , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
The biotransformations of cholic acid (1a), deoxycholic acid (1b), and hyodeoxycholic acid (1c) to bendigoles and other metabolites with bacteria isolated from the rural slaughterhouse of Cayambe (Pichincha Province, Ecuador) were reported. The more active strains were characterized, and belong to the genera Pseudomonas and Rhodococcus. Various biotransformation products were obtained depending on bacteria and substrates. Cholic acid (1a) afforded the 3-oxo and 3-oxo-4-ene derivatives 2a and 3a (45% and 45%, resp.) with P. mendocina ECS10, 3,12-dioxo-4-ene derivative 4a (60%) with Rh. erythropolis ECS25, and 9,10-secosteroid 6 (15%) with Rh. erythropolis ECS12. Bendigole F (5a) was obtained in 20% with P. fragi ECS22. Deoxycholic acid (1b) gave 3-oxo derivative 2b with P. prosekii ECS1 and Rh. erythropolis ECS25 (20% and 61%, resp.), while 3-oxo-4-ene derivative 3b was obtained with P. prosekii ECS1 and P. mendocina ECS10 (22% and 95%, resp.). Moreover, P. fragi ECS9 afforded bendigole A (8b; 80%). Finally, P. mendocina ECS10 biotransformed hyodeoxycholic acid (1c) to 3-oxo derivative 2c (50%) and Rh. erythropolis ECS12 to 6α-hydroxy-3-oxo-23,24-dinor-5ß-cholan-22-oic acid (9c, 66%). Bendigole G (5c; 13%) with P. prosekii ECS1 and bendigole H (8c) with P. prosekii ECS1 and Rh. erythropolis ECS12 (20% and 16%, resp.) were obtained.
Assuntos
Ácidos e Sais Biliares/metabolismo , Hidroxiesteroides/metabolismo , Pseudomonas/metabolismo , Rhodococcus/metabolismo , Matadouros , Equador , Hidroxiesteroides/química , Conformação MolecularRESUMO
Arthrospira platensis, known as spirulina, is a cyanobacterium with multiple nutritional benefits, as it contains substantial amounts of proteins, fatty acids, and pigments. However, the production of this microalga has faced significant challenges, primarily related to the cost and composition of the required culture medium for its optimal growth. This study focused on optimizing two nitrogen sources (urea and potassium nitrate) to maximize the growth of A. platensis and the production of phycocyanin, a photosynthetic pigment of significant commercial value. Optimization was performed using the response surface methodology (RSM) with a central composite design (CCD). Analysis of variance (ANOVA) was employed to validate the model, which revealed that the different concentrations of urea were statistically significant (p < 0.05) for biomass and phycocyanin production. However, potassium nitrate (KNO3) showed no significant influence (p > 0.05) on the response variables. The RSM analysis indicated that the optimal concentrations of KNO3 and urea to maximize the response variables were 3.5 g L-1 and 0.098 g L-1, respectively. This study offers valuable perspectives for the efficient production of A. platensis while reducing production costs for its cultivation on a larger scale.
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PURPOSE OF REVIEW: Familial Hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that all people with familial hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. RECENT FINDINGS: In the last year, several studies have been published focusing on the contribution of diabetes to familial hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. SUMMARY: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.
Assuntos
Doenças Cardiovasculares , Fatores de Risco de Doenças Cardíacas , Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/complicações , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Medição de Risco/métodos , Fatores de RiscoRESUMO
PIM serine/threonine kinases are overexpressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa-associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.
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Inibidores Enzimáticos/farmacologia , Terapia Genética/métodos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfonodos/patologia , Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Tonsila Palatina/patologia , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.
Assuntos
Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/biossíntese , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunoterapia , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de TecidosRESUMO
Introduction: Policymakers, health practitioners, and other key partners are increasingly focused on ensuring that clients of food assistance programs have positive experiences, a key aspect of high-quality programming. The objectives of this review are to describe the experiences of clients participating in food assistance programs in the United States (US) and to identify ways that these programs promote or hinder positive experiences. Methods and analysis: We will conduct a qualitative evidence synthesis with partners from food security organizations and community members. Peer-reviewed literature will be systematically searched in Scopus, CINAHL, and AGRICOLA. To identify grey literature, we will use Google's programmable search engine. This review will consider sources that present results of primary qualitative studies that focus on at least one food assistance program in the US and explore the perspectives of adult clients. Only sources published in English or Spanish from 2007 onward will be included. Multiple reviewers will screen articles for inclusion and extract data from articles that meet the inclusion criteria, using a structured data extraction tool. Thematic synthesis or meta-ethnography may be appropriate approaches for synthesizing the extracted data. The final selection of synthesis method will be determined once the set of primary qualitative studies to be included in the review is complete and the type of data presented in these studies is known. We will assess the methodological quality of the included studies using the CASP (Critical Appraisal Skills Programme) tool for qualitative studies and assess the confidence in the review findings using the GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach. Discussion: The findings of this review will inform the development of measures to assess client experience and quality improvement efforts.
Assuntos
Assistência Alimentar , Humanos , Estados Unidos , Adulto , Pesquisa Qualitativa , Melhoria de Qualidade , Ferramenta de Busca , Revisões Sistemáticas como AssuntoRESUMO
Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions. We discovered that, upon activation, p38γ and p38δ cooperatively increase the susceptibility to stress-induced VF. Mechanistically, our data indicate that activated p38γ and p38δ phosphorylate ryanodine receptor 2 (RyR2) disrupt Kv4.3 channel localization, promoting sarcoplasmic reticulum calcium leak, Ito current reduction and action potential duration prolongation. In turn, this led to aberrant intracellular calcium handling, premature ventricular complexes and enhanced susceptibility to VF. Blocking this pathway protected genetically modified animals from VF development and reduced the VF duration in aged animals. These results indicate that p38γ and p38δ are a potential therapeutic target for sustained VF prevention.
Assuntos
Proteína Quinase 12 Ativada por Mitógeno , Canal de Liberação de Cálcio do Receptor de Rianodina , Fibrilação Ventricular , Animais , Proteína Quinase 12 Ativada por Mitógeno/metabolismo , Proteína Quinase 12 Ativada por Mitógeno/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/genética , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Proteína Quinase 13 Ativada por Mitógeno/metabolismo , Proteína Quinase 13 Ativada por Mitógeno/genética , Fosforilação , Miócitos Cardíacos/metabolismo , Masculino , Ativação Enzimática , Camundongos , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/genética , Complexos Ventriculares Prematuros/metabolismo , Retículo Sarcoplasmático/metabolismo , Camundongos Knockout , Humanos , Sinalização do Cálcio , Fatores EtáriosRESUMO
INTRODUCTION: Heterozygous familial hypercholesterolaemia (heFH) is the most common monogenic cause of premature atherosclerotic cardiovascular disease. The precise diagnosis of heFH is established by genetic testing. This systematic review will investigate the risk factors that predict cardiovascular events in patients with a genetic diagnosis of heFH. METHODS AND ANALYSIS: Our literature search will cover publications from database inception until June 2023. We will undertake a search of CINAHL (trial), clinicalKey, Cochrane Library, DynaMed, Embase, Espacenet, Experiments (trial), Fisterra, ÍnDICEs CSIC, LILACS, LISTA, Medline, Micromedex, NEJM Resident 360, OpenDissertations, PEDro, Trip Database, PubPsych, Scopus, TESEO, UpToDate, Web of Science and the grey literature for eligible studies. We will screen the title, abstract and full-text papers for potential inclusion and assess the risk of bias. We will employ the Cochrane tool for randomised controlled trials and non-randomised clinical studies and the Newcastle-Ottawa Scale for assessing the risk of bias in observational studies. We will include full-text peer-reviewed publications, reports of a cohort/registry, case-control and cross-sectional studies, case report/series and surveys related to adults (≥18 years of age) with a genetic diagnostic heFH. The language of the searched studies will be restricted to English or Spanish. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. Based on the data available, the authors will determine whether the data can be pooled in meta-analyses. ETHICS AND DISSEMINATION: All data will be extracted from published literature. Hence, ethical approval and patient informed consent are not required. The findings of the systematic review will be submitted for publication in a peer-reviewed journal and presentation at international conferences. PROSPERO REGISTRATION NUMBER: CRD42022304273.
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Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Humanos , Estudos Transversais , Fatores de Risco , Doenças Cardiovasculares/genética , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/genética , Revisões Sistemáticas como AssuntoRESUMO
Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. AIMS: To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. MATERIALS AND METHODS: One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. RESULTS: There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2, HFF1A, ILI8R1, EIF2AK2, TXNRD2, PPARA, NDUFS2 and ERN1. CONCLUSIONS: Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them.
Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Haplótipos , Obesidade/genética , Alelos , Polimorfismo de Nucleotídeo Único , Estudos de Casos e ControlesRESUMO
OBJECTIVES: To test the safety of the diode light therapy and evaluate the advantages of the interferential effect of two light probes versus a conventional light probe in the relief of shoulder pain and disability caused by shoulder tendinopathies. DESIGN: Randomized single-blind pilot study. SETTING: Clinical electrotherapy unit. PARTICIPANTS: A total of 30 patients with shoulder pain from tendinopathies. INTERVENTIONS: The patients were randomly assigned into two groups. Group 1 (n = 15) received interferential light therapy generated by two independent and identical cluster probes composed of light emitting and superluminescent diodes. Similarly, two applicators were applied in group 2 (n = 15), but only one was active, as in conventional clinical therapy. Each multi-diode cluster probe was composed of seven light-emitting diodes at 600 nm and 12 superluminescent diodes at 950 nm. MAIN OUTCOME MEASURES: Pain was evaluated by visual analogue scale (VAS) at day, at night and during several shoulder movements. Shoulder functional status was measured by means of the University California Los Angeles scale (UCLA). RESULTS: Comparison between both treatments using the Mann-Whitney U-test showed better results for the interferential treatment. There were significant differences in pain reduction during abduction (P < 0.05) and external rotation (P < 0.05), with pain reductions in abduction and external rotation of 1.5 (± 1.3) and 0.5 (± 1.0) respectively. CONCLUSION: Interferential light therapy was safe and effective regarding the shoulder pain reduction during abduction and external rotation movements. The estimated size sample needed for future two-treatment parallel-design studies will require about 60 patients.
Assuntos
Fototerapia/métodos , Dor de Ombro/reabilitação , Tendinopatia/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fototerapia/efeitos adversos , Projetos Piloto , Segurança , Método Simples-CegoRESUMO
BACKGROUND: Familial Hypercholesterolemia is the most frequent genetic cause of premature coronary heart disease. The delay in the diagnosis prevents the correct early treatment. There are no effective screening strategies at the national level that ensure a correct diagnosis. OBJECTIVE: To determine the capacity of a centralized laboratory for the diagnosis of Familial Hypercholesterolemia through the creation of a health program for population screening in the province of Huelva. METHOD: Active search of patients with primary hypercholesterolemia through the blood tests carried out in the reference laboratories with results of low-density lipoprotein cholesterol greater than 200â¯mg/dl and assessment in the Lipid Unit of Huelva to identify index cases, with subsequent family cascade screening. RESULTS: 37,440 laboratory tests with lipid profile were examined. After screening, 846 individuals were seen in the Lipid Unit, of which they were diagnosed according to criteria of the Dutch Lipid Clinic Network as possible 654 and probable/definitive 192 individuals, representing 1.74% and 0.51% of the general population examined respectively. CONCLUSIONS: The point prevalence of Familial Hypercholesterolemia in patients submitted to laboratory lipid profile tests was 1:195, higher compared to the prevalence of Familial Hypercholesterolemia in the general population (based on 1 in 200-300). The opportunistic search strategy of the index case through a laboratory alert and centralized screening is an efficient strategy to implement a national screening for the diagnosis of Familial Hypercholesterolemia.
Assuntos
Hiperlipoproteinemia Tipo II , LDL-Colesterol , Doença da Artéria Coronariana , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Programas de Rastreamento , Prevalência , EspanhaRESUMO
To evaluate the pathogenic mechanisms and transmission routes involved in KSHV infection in 22 Cuban individuals who maintained close contact with epidemic KS patients, real-time PCR was used to quantify KSHV-DNA in clinical samples of plasma, saliva and peripheral blood mononuclear cells (PBMC). KSHV-DNA was detected in 72.7% (16/22) of the contacts. The highest levels of KSHV load were detected in saliva, followed by PBMC (average log copies/100 ng DNA = 1.28 and 1.12), while significantly lower levels were detected in plasma (average log copies/ml = 0.37). Two of three intra-domiciliary and two serodiscordant sexual contacts of AIDS-KS patients were infected with KSHV. The rate of KSHV-DNA detection in saliva and PBMC samples in men who have sex with men (MSM) was significantly higher than in heterosexuals (HT) (p = 0.014). MSM were more likely to harbor KSHV-DNA in saliva when compared with HT individuals (OR 4.33; 95% CI 1.117-16.8). These results emphasize that, in Cuba, KSHV horizontal transmission through saliva may occur, although homosexual behavior may predispose an individual to KSHV acquisition. Even in the absence of disease, KSHV could cause an asymptomatic systemic infection in individuals who maintain close contact with AIDS-KS patients.
Assuntos
Infecções por Herpesviridae/transmissão , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/isolamento & purificação , Carga Viral , Cuba , DNA Viral/isolamento & purificação , Transmissão de Doença Infecciosa , Feminino , Homossexualidade Masculina , Humanos , Leucócitos Mononucleares/virologia , Masculino , Plasma/virologia , Reação em Cadeia da Polimerase , Saliva/virologiaRESUMO
To ascertain the relationship between the perimetric differences obtained between the limbs and the type of fluoroscopic pattern observed by Indocyanine green (ICG) lymphography in patients with upper limb lymphedema.A correlational descriptive study was carried out in 19 patients with upper limb lymphedema secondary to breast cancer. The perimetric increase was recorded in 11 anatomical regions after ICG injection, fluoroscopic patterns were identified using an infrared camera. The ICG patterns were categorized into worse (stardust, diffuse) or better (linear, splash) patterns.The pattern coincidence between the anterior and posterior regions of the edematous extremities was 45%. At the wrist level, a difference of 2âcm was associated with the presence of a worse fluoroscopic pattern, whereas perimeter differences of 4.25âcm in the elbow and 2.25âcm in the arm (12âcm from the epicondyle) were associated with the presence of a better fluoroscopic pattern.The perimetric differences observed between the healthy and affected upper limbs in 4 specific anatomical areas allowed us to predict the type of fluoroscopic pattern. ICG lymphography has facilitated the study of the posterior regions of edema, which are difficult to visualize using other imaging techniques.
Assuntos
Verde de Indocianina/administração & dosagem , Vasos Linfáticos/diagnóstico por imagem , Linfedema/etiologia , Linfografia/métodos , Testes de Campo Visual/métodos , Adulto , Idoso , Neoplasias da Mama/complicações , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Fluoroscopia/métodos , Fluoroscopia/estatística & dados numéricos , Humanos , Vasos Linfáticos/patologia , Linfedema/classificação , Linfedema/patologia , Pessoa de Meia-Idade , Espanha/epidemiologia , Extremidade Superior/anatomia & histologia , Extremidade Superior/diagnóstico por imagemRESUMO
Indocyanine green (ICG) lymphography is used to evaluate the lymphatic function before and after pneumatic compression or post-manual lymphatic drainage. The aim of this study was to ascertain the changes in the fluoroscopic pattern produced by the provision of complex physical therapy. This prospective analytic (pretest-posttest) study was conducted in 19 patients with upper lymphedema secondary to breast cancer. Nine patients were excluded due to ICG found after 3 weeks. The ICG patterns were analyzed under basal conditions and after three weeks of treatment. After the treatment, 45% of the patients presented tracer remains in the affected limb, and this finding was significantly related to time of the lymphedema development. In one subject, the patterns remain unchanged or cannot be defined. Three of the ten patients observed present the worsening of at least 1 of the patterns and in the rest of the subjects, six cases, the improvement of the patterns is observed. In 60% of the cases, the most severe pattern reversed towards slight (splash) cases, and moderate cases reversed towards a slight case in 70% of cases. Therefore, after treatment with complex physical therapy, the pathological patterns observed in the pretest, which evolved positively, reverted their severity toward milder disease patterns or towards normality.