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1.
Nat Commun ; 13(1): 7791, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543778

RESUMO

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.


Assuntos
Biotina , Doença de Huntington , Oligodendroglia , Tiamina , Animais , Humanos , Camundongos , Biotina/metabolismo , Biotina/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Doença de Huntington/metabolismo , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Oligodendroglia/metabolismo , Núcleo Solitário/metabolismo , Tiamina/metabolismo , Tiamina/farmacologia
2.
Int J Mol Sci ; 23(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35897642

RESUMO

Glaucomatous optic neuropathy is the leading cause of irreversible blindness in the world. The chronic disease is characterized by optic nerve degeneration and vision field loss. The reduction of intraocular pressure remains the only proven glaucoma treatment, but it does not prevent further neurodegeneration. There are three major classes of cells in the human optic nerve head (ONH): lamina cribrosa (LC) cells, glial cells, and scleral fibroblasts. These cells provide support for the LC which is essential to maintain healthy retinal ganglion cell (RGC) axons. All these cells demonstrate responses to glaucomatous conditions through extracellular matrix remodeling. Therefore, investigations into alternative therapies that alter the characteristic remodeling response of the ONH to enhance the survival of RGC axons are prevalent. Understanding major remodeling pathways in the ONH may be key to developing targeted therapies that reduce deleterious remodeling.


Assuntos
Glaucoma , Disco Óptico , Doenças do Nervo Óptico , Glaucoma/metabolismo , Glaucoma/terapia , Humanos , Pressão Intraocular , Disco Óptico/metabolismo , Doenças do Nervo Óptico/metabolismo , Células Ganglionares da Retina
3.
Phytomedicine ; 103: 154237, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35688101

RESUMO

BACKGROUND: With increased consumer demand in Europe for natural and efficacious health products, the use of herbal products in the market is rising. Products of Chinese herbal medicine (CHM) could greatly expand European consumer options; however, only seven herbal medicinal products (HMPs) based on CHM formulae have been registered in the European Union (EU) since 2012. PURPOSE: This study reviews the ten-year registration status of HMPs based on CHM formulae in Europe and identifies major challenges and possible solutions for pharmaceutical companies seeking market access for new HMPs. METHODS: An overview of relevant EU regulations identifies pathways to market access in EU countries for CHM products. A discussion of successful attempts to register HMPs based on CHM formulae since 2012 highlights specific challenges that applicants can expect to face. RESULTS: CHM products can enter the EU market as HMPs through the full or well-established use marketing authorization, or through the simplified registration procedure. Alternatively, some CHM products have entered the market as dietary supplements, nutritional foods, and agricultural products; however, under these categories, claims for medicinal use cannot be advertised. Since the registration of the first CHM product, Diao Xin Xue Kang (with the single component of Dioscorea nipponica rhizome), in 2012, only six other HMPs based on CHM formulae have been successfully registered. Among these, four are mono-component products. The remaining two products contain combinations of several herbal ingredients. It is more difficult to register combination products than mono-component products, due to their more complex composition and differences in registration requirements (esp. concerning establishing indications) in China and Europe. CONCLUSIONS: To promote the successful registration of CHM products in Europe, pharmaceutical companies are advised to: demonstrate full control of, and the ability to test, their supply chain and manufacturing procedures following the guidance of European competent authorities; carefully adhere to all steps of the registration process and advices from European competent authorities; take the medication habits and pharmaceutical needs of European market into consideration; and establish collaboration with European local organizations, as appropriate.


Assuntos
Medicina Herbária , Plantas Medicinais , China , Europa (Continente) , Humanos , Fitoterapia , Políticas
4.
World Neurosurg ; 158: e184-e195, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34757211

RESUMO

OBJECTIVE: In the present retrospective cohort analysis, we examined the differences in baseline characteristics and peri- and postoperative outcomes stratified by 3 groups: cannabis abuse or dependence versus none, surgical versus endovascular treatment, and unruptured and ruptured intracranial aneurysms. METHODS: A study population of 26,868 patients was defined using the 2009-2016 National Inpatient Sample database. The baseline characteristics were compared between the cannabis and no-cannabis groups, and the traits that differed significantly were factored into the multivariate analysis using 1:1 propensity score matching. The matched groups were analyzed to compare the cannabis and no-cannabis cohorts for the following endpoints: mortality, length of stay, discharge disposition, total hospital charges, and several peri- and postoperative outcomes. RESULTS: In the surgically and endovascularly treated groups for unruptured intracranial aneurysms, those in the cannabis group were more likely to be male and younger and to smoke tobacco than were those in the no-cannabis group. After matching, no significant endpoint differences were noted. Similarly, in the surgically and endovascularly treated ruptured aneurysm groups, those in the cannabis group were more likely to be male and younger and to smoke tobacco. After matching, the cannabis group within the endovascular treatment group had had a longer length of stay and were more likely to have developed any hydrocephalus, obstructive hydrocephalus, sepsis, and acute kidney injury. Those in the cannabis group who had undergone surgery were more likely to have developed any hydrocephalus, specifically, communicating hydrocephalus. CONCLUSIONS: The cannabis group with ruptured intracranial aneurysms was more likely to experience certain adverse outcomes after surgical or endovascular treatment compared with the no-cannabis group. However, such was not the case for cannabis abusers treated for unruptured aneurysms.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Hidrocefalia , Aneurisma Intracraniano , Abuso de Maconha , Aneurisma Roto/cirurgia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Hidrocefalia/complicações , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Tempo de Internação , Masculino , Abuso de Maconha/complicações , Abuso de Maconha/epidemiologia , Abuso de Maconha/terapia , Estudos Retrospectivos , Instrumentos Cirúrgicos , Resultado do Tratamento
5.
Glob Health Action ; 14(1): 1898131, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33797347

RESUMO

There are estimated two million traditional healers in sub-Saharan Africa (SSA), with more than 10% (200,000) working in South Africa. Traditional healers in SSA are frequently exposed to bloodborne pathogens through the widespread practice of traditional 'injections', in which the healers perform dozens of subcutaneous incisions to rub herbs directly into the bloodied tissue with their hands. Healers who report exposure to patient blood have a 2.2-fold higher risk of being HIV-positive than those who do not report exposure. We propose a randomized controlled trial (61 healers in the intervention group and 61 healers in the control group) in Mpumalanga Province. Healers will receive personal protective equipment (PPE) education and training, general HIV prevention education, and three educational outreach visits at the healer's place of practice to provide advice and support for PPE use and disposal. Healers in the control arm will be trained by health care providers, while participants in the intervention arm will receive training and outreach from a team of healers who were early adopters of PPE. We will evaluate intervention implementation using data from surveys, observation, and educational assessments. Implementation outcomes of interest include acceptability and feasibility of PPE use during clinical encounters and fidelity of PPE use during treatments that involve blood exposure. We will test our two intervention strategies to identify an optimal strategy for PPE education in a region with high HIV prevalence.


Assuntos
Medicinas Tradicionais Africanas , Equipamento de Proteção Individual , Pessoal de Saúde , Humanos , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , África do Sul
6.
Nitric Oxide ; 111-112: 37-44, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831566

RESUMO

Dietary nitrate (NO3-) supplementation via beetroot juice (BR) has been reported to lower oxygen cost (i.e., increased exercise efficiency) and speed up oxygen uptake (VO2) kinetics in untrained and moderately trained individuals, particularly during conditions of low oxygen availability (i.e., hypoxia). However, the effects of multiple-day, high dose (12.4 mmol NO3- per day) BR supplementation on exercise efficiency and VO2 kinetics during normoxia and hypoxia in well-trained individuals are not resolved. In a double-blinded, randomized crossover study, 12 well-trained cyclists (66.4 ± 5.3 ml min-1∙kg-1) completed three transitions from rest to moderate-intensity (~70% of gas exchange threshold) cycling in hypoxia and normoxia with supplementation of BR or nitrate-depleted BR as placebo. Continuous measures of VO2 and muscle (vastus lateralis) deoxygenation (ΔHHb, using near-infrared spectroscopy) were acquired during all transitions. Kinetics of VO2 and deoxygenation (ΔHHb) were modeled using mono-exponential functions. Our results showed that BR supplementation did not alter the primary time constant for VO2 or ΔHHb during the transition from rest to moderate-intensity cycling. While BR supplementation lowered the amplitude of the VO2 response (2.1%, p = 0.038), BR did not alter steady state VO2 derived from the fit (p = 0.258), raw VO2 data (p = 0.231), moderate intensity exercise efficiency (p = 0.333) nor steady state ΔHHb (p = 0.224). Altogether, these results demonstrate that multiple-day, high-dose BR supplementation does not alter exercise efficiency or oxygen uptake kinetics during normoxia and hypoxia in well-trained athletes.


Assuntos
Beta vulgaris/química , Ciclismo , Exercício Físico , Sucos de Frutas e Vegetais , Nitratos/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Hipóxia/metabolismo , Cinética , Músculo Esquelético/metabolismo , Nitratos/administração & dosagem , Oxigênio/química , Oxigênio/metabolismo , Raízes de Plantas/química
7.
AIDS Care ; 33(10): 1316-1320, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32799661

RESUMO

In 2018, nearly 800,000 HIV positive individuals in South Africa were unaware of their status. Traditional healers see patients who avoid health clinics, including those who refuse HIV testing. This manuscript details the results of a qualitative study to understand traditional healer perspectives on performing healer-initiated HIV counseling and testing HIV in rural South Africa. We conducted 30 structured in-depth interviews between April and June 2019 to elicit traditional healer attitudes towards partnering with local health services to perform HIV counseling and testing with their patients. Healers reported that while some patients are open about their HIV status, others lie about it due to stigma. This creates challenges with concurrent treatment, which healers believe leads to allopathic and/or traditional medication treatment failure. Most healers expressed both an interest and a willingness to perform HIV counseling and testing. Healers felt that by performing testing in the community, it would overcome issues related to HIV stigma, as well as a lack of confidentiality and trust with health care workers at the clinic. Trained traditional healers may be able to bridge the testing gap between "non-testers" and the allopathic health system, essentially "opening" thousands of new testing locations with little financial investment.


Assuntos
Infecções por HIV , Medicinas Tradicionais Africanas , Aconselhamento , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Humanos , População Rural , Estigma Social , África do Sul
8.
AIDS ; 34(15): 2313-2317, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33048882

RESUMO

OBJECTIVE: To understand the risk of HIV acquisition through occupational exposure among rural South African traditional healers, notably via the practice of traditional skin incisions with razors. DESIGN: A random sample of traditional healers living in South Africa participated in a cross-sectional survey that included a rapid HIV test. SETTING: Rural Bushbuckridge district of Mpumalanga, South Africa. PARTICIPANTS: Traditional healers. INTERVENTION: Pretest counseling, posttest counseling, and referral to care if HIV seropositive. MAIN OUTCOME MEASURE(S): HIV infection. RESULTS: Among healers who reported a previous positive test result or accepted an HIV test (96%), HIV prevalence was 30% (95% confidence interval: 23-37%). During their careers, 98% of healers reported conducting at least one 'vaccination' (as traditional incisions are called), 32% reported always using gloves when conducting these procedures, 29 (14%) reported patient blood touching their bare skin. Healers who reported exposure to patient blood had a higher HIV prevalence than their nonexposed colleagues (adjusted risk ratio: 2.35, 95% confidence interval: 1.55-3.56, P = 0.001). CONCLUSION: Nearly all traditional healers are routinely performing minimally invasive skin incisions that could expose them to patient blood. The lack of training and access to personal protective equipment increase their risk of acquisition of blood-borne pathogens, including HIV. Given the widespread practice of traditional skin incisions across southern Africa, and the higher levels of HIV among traditional healers exposed to patient blood, it is likely that traditional healers are a hitherto unrecognized key population at disproportionate risk of acquiring HIV.


Assuntos
Infecções por HIV , Medicinas Tradicionais Africanas , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , África do Sul/epidemiologia
10.
Front Immunol ; 11: 1447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760397

RESUMO

Alcoholism is one of the leading and increasingly prevalent reasons of liver associated morbidity and mortality worldwide. Alcoholic hepatitis (AH) constitutes a severe disease with currently no satisfying treatment options. Lipoxin A4 (LXA4), a 15-lipoxygenase (ALOX15)-dependent lipid mediator involved in resolution of inflammation, showed promising pre-clinical results in the therapy of several inflammatory diseases. Since inflammation is a main driver of disease progression in alcoholic hepatitis, we investigated the impact of endogenous ALOX15-dependent lipid mediators and exogenously applied LXA4 on AH development. A mouse model for alcoholic steatohepatitis (NIAAA model) was tested in Alox12/15+/+ and Alox12/15-/- mice, with or without supplementation of LXA4. Absence of Alox12/15 aggravated parameters of liver disease, increased hepatic immune cell infiltration in AH, and elevated systemic neutrophils as a marker for systemic inflammation. Interestingly, i.p. injections of LXA4 significantly lowered transaminase levels only in Alox12/15-/- mice and reduced hepatic immune cell infiltration as well as systemic inflammatory cytokine expression in both genotypes, even though steatosis progressed. Thus, while LXA4 injection attenuated selected parameters of disease progression in Alox12/15-/- mice, its beneficial impact on immunity was also apparent in Alox12/15+/+ mice. In conclusion, pro-resolving lipid mediators may be beneficial to reduce inflammation in alcoholic hepatitis.


Assuntos
Araquidonato 12-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/genética , Hepatite Alcoólica/metabolismo , Inflamação/metabolismo , Lipoxinas/metabolismo , Fígado/fisiologia , Neutrófilos/imunologia , Animais , Modelos Animais de Doenças , Hepatite Alcoólica/genética , Humanos , Inflamação/genética , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ativação de Neutrófilo/genética
11.
BMC Health Serv Res ; 20(1): 655, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669101

RESUMO

BACKGROUND: Traditional healers are frequently exposed to hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) through the widespread practice of traditional "injections", in which the healer performs dozens of subcutaneous incisions using a razor blade to rub herbs directly into bloodied tissue. An average healer in Agincourt, a rural northeastern sub-district in Mpumalanga province, South Africa, experiences approximately 1500 occupational blood exposures over the course of their lifetime. Healers in Agincourt have an HIV prevalence of 30% compared to 19% in the general population, and healers who report exposure to patient blood have an adjusted 2.4-fold higher odds of being HIV-positive than those with no exposure. Although research on appropriate PPE use has been well documented for allopathic care providers, little is known about the practices of traditional healers. METHODS: This qualitative study was conducted with 30 traditional healers who practice in the rural Bushbuckridge sub-district of Mpumalanga province, northeastern South Africa. We elicited traditional healer attitudes towards glove use during traditional treatments - including patient baths, injections, or other treatments that exposed healers to patient blood or open sores. RESULTS: While 90% of healers reported using latex gloves during some treatments, the majority do not use them regularly. Most employ a combination of gloves, plastic shopping bags, bread bags, paper, and sticks to prevent blood exposure. Healers reported plastic bags slipping or breaking during procedures, exposing them to patient blood. Only three healers consistently used gloves, regardless of the cost. CONCLUSIONS: Inadequate PPE use and high HIV prevalence make traditional healers particularly susceptible to contracting HIV in rural South Africa. Despite positive attitudes, consistent glove use remains low due to financial constraints and glove availability. Addressing issues of accessibility and cost of gloves for traditional healers could have a significant impact on the adherence to PPE and, in turn, reduce new HIV infections among this high-risk group.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Infecções por HIV/prevenção & controle , Medicinas Tradicionais Africanas , Equipamento de Proteção Individual/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Humanos , Injeções , Masculino , Prevalência , Pesquisa Qualitativa , Serviços de Saúde Rural , População Rural , África do Sul/epidemiologia , Ferida Cirúrgica
12.
J Clin Neurosci ; 71: 93-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31771803

RESUMO

A unique challenge in some brain tumor patients is the fact that tumors arising in certain areas of the brain involve the neural structures of consciousness or alertness, limiting the patient's ability to participate in rehabilitation following surgery. A critical question is whether neurostimulant therapy can help patients participate in rehabilitation efforts. We performed a retrospective review of all patients undergoing brain tumor surgery by the senior author from 2012 to 2018. We limited this study to patients with tumors occupying critical structures related to consciousness, alertness, and motor initiation. A combination of methylphenidate and levodopa/carbidopa was used to monitor the progress of patients through neurorehabilitation efforts. We identified 101 patients who experienced an inability to participate in rehabilitation (ITPR) in the post-operative period. Of these, 86 patients (85%) were treated with methylphenidate and levodopa/carbidopa. Cases of ITPR were related to dysfunction of the brainstem (12/86 cases, 14%), thalamus (17/86 cases, 20%), hypothalamus (14/86 cases, 16%), basal ganglia (13/86 cases, 15%), and medial frontal lobe (30/86 cases, 35%). Of the 86 individuals treated, 47/86 patients (55%) showed early improvement in their ability to participate with rehabilitation. At three month follow-up, 58/86 patients (67%) had returned to living independently or were at least interactive and cooperative during follow-up examination. This feasibility report suggests that combined therapy with methylphenidate and levodopa/carbidopa may help patients participate in neurorehabilitation efforts in the immediate post-operative period following brain tumor surgery. Randomized, controlled clinical trials are needed to explore this concept more thoroughly.


Assuntos
Neoplasias Encefálicas/reabilitação , Carbidopa/uso terapêutico , Levodopa/uso terapêutico , Metilfenidato/uso terapêutico , Adulto , Gânglios da Base , Encéfalo/cirurgia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Suplementos Nutricionais , Combinação de Medicamentos , Feminino , Lobo Frontal , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Período Pós-Operatório , Estudos Retrospectivos
13.
Health Promot Pract ; 21(4): 633-641, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-30442018

RESUMO

The purpose of this study was to identify adolescents' consequence, referent, and circumstance beliefs about trying to meditate at least twice in the next week in order to inform subsequent meditation intervention design. A survey based on reasoned action approach (RAA) constructs was developed and pilot-tested. Thereafter, adolescents (N = 129), recruited from a northeastern U.S. high school, responded to open-ended survey questions eliciting beliefs underlying intention to try meditating. Thematic analysis was executed to examine beliefs and frequencies of beliefs. Five types of salient meditation beliefs were identified: advantages (e.g., reduces stress, increases relaxation, improves focus), disadvantages (e.g., slows everything down), supporters and disapprovers (e.g., family and friends), and facilitating circumstances (e.g., more time, fewer distractions). Adolescents recognize meditation as having health benefits but as also taking time. They further viewed meditation as socially acceptable but need sufficient time and a conducive environment to try it. To be effective, interventions designed to promote adolescents' self-regulation through meditation should address identified salient beliefs.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Meditação/psicologia , Pensamento , Adolescente , Feminino , Humanos , Intenção , Masculino , Projetos Piloto , Relaxamento/psicologia , Instituições Acadêmicas , Estresse Psicológico/prevenção & controle , Inquéritos e Questionários
14.
J Am Heart Assoc ; 8(15): e012862, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31378125

RESUMO

See Article Bodar et al.


Assuntos
Fibrilação Atrial , Café , Humanos
15.
Physiol Rep ; 7(13): e14162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31293100

RESUMO

Unaccustomed eccentric exercise leads to impaired microvascular function but the underlying mechanism is unknown. In this study, we evaluated the role of oxidative stress and of nitric oxide (NO) bioavailability. Thirty young men and women performed eccentric contractions of the tibialis anterior (TA) muscle (ECC), with the contralateral leg serving as nonexercising control (CON). Participants were randomized into three groups ingesting an antioxidant cocktail (AO), beetroot juice (BR) or placebo 46 h postexercise. At baseline and 48 h postexercise, hyperemic responses to brief muscle contractions and 5 min of cuff occlusion were assessed bilaterally in the TA muscles using blood oxygen level dependent (BOLD) magnetic resonance imaging. Eccentric contractions resulted in delayed time-to-peak (~22%; P < 0.001), blunted peak (~21%; P < 0.001) and prolonged time-to-half relaxation (~12%, P < 0.001) in the BOLD response to brief contractions, with no effects of AO or BR, and no changes in CON. Postocclusive time-to-peak was also delayed (~54%; P < 0.001) in ECC, with no effects of AO or BR, and no changes in CON. Impaired microvascular reactivity after eccentric contractions is confined to the exercised tissue, and is not restored with acute ingestion of AO or BR. Impairments in microvascular reactivity after unaccustomed eccentric contractions may result from structural changes within the microvasculature that can diminish muscle blood flow regulation during intermittent activities requiring prompt adjustments in oxygen delivery.


Assuntos
Antioxidantes/farmacologia , Beta vulgaris/química , Sucos de Frutas e Vegetais , Hiperemia/prevenção & controle , Contração Isométrica , Músculo Esquelético/fisiologia , Vasodilatação , Adulto , Antioxidantes/administração & dosagem , Feminino , Humanos , Hiperemia/tratamento farmacológico , Masculino , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos
16.
J Cardiovasc Electrophysiol ; 30(10): 1939-1948, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31257683

RESUMO

INTRODUCTION: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function. METHODS: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs. RESULTS: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy. CONCLUSIONS: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression.


Assuntos
Potenciais de Ação , Arritmias Cardíacas/diagnóstico , Cardiomiopatias/diagnóstico , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Sarcoidose/diagnóstico , Função Ventricular Esquerda , Função Ventricular Direita , Idoso , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Progressão da Doença , Cardioversão Elétrica/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sarcoidose/mortalidade , Sarcoidose/fisiopatologia , Sarcoidose/terapia , Volume Sistólico , Sístole , Fatores de Tempo
17.
J Ind Microbiol Biotechnol ; 46(11): 1531-1545, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31270700

RESUMO

The economic viability of the biorefinery concept is limited by the valorization of lignin. One possible method of lignin valorization is biological upgrading with aromatic-catabolic microbes. In conjunction, lignin monomers can be produced by fast pyrolysis and fractionation. However, biological upgrading of these lignin monomers is limited by low water solubility. Here, we address the problem of low water solubility with an emulsifier blend containing approximately 70 wt% Tween® 20 and 30 wt% Span® 80. Pseudomonas putida KT2440 grew to an optical density (OD600) of 1.0 ± 0.2 when supplied with 1.6 wt% emulsified phenolic monomer-rich product produced by fast pyrolysis of red oak using an emulsifier dose of 0.076 ± 0.002 g emulsifier blend per g of phenolic monomer-rich product. This approach partially mitigated the toxicity of the model phenolic monomer p-coumarate to the microbe, but not benzoate or vanillin. This study provides a proof of concept that processing of biomass-derived phenolics to increase aqueous availability can enhance microbial utilization.


Assuntos
Fenóis/metabolismo , Óleos de Plantas/metabolismo , Polifenóis/metabolismo , Pseudomonas putida/metabolismo , Biomassa , Fracionamento Químico , Emulsões , Lignina/metabolismo
18.
Nitric Oxide ; 85: 44-52, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30685420

RESUMO

Dietary nitrate (NO3-) supplementation via beetroot juice (BR) is known to improve endurance performance in untrained and moderately trained individuals. However, conflicting results exist in well-trained individuals. Evidence suggests that the effects of NO3- are augmented during conditions of reduced oxygen availability (e.g., hypoxia), thereby increasing the probability of performance improvements for well-trained athletes in hypoxia vs. normoxia. This randomized, double-blinded, counterbalanced-crossover study examined the effects of 7 days of BR supplementation with 12.4 mmol NO3- per day on 10-km cycling time trial (TT) performance in 12 well-trained cyclists in normoxia (N) and normobaric hypoxia (H). Linear mixed models for repeated measures revealed increases in plasma NO3- and NO2- after supplementation with BR (both p < 0.001). Further, TT performance increased with BR supplementation (∼1.6%, p < 0.05), with no difference between normoxia and hypoxia (p = 0.92). For respiratory variables there were significant effects of supplementation on VO2 (p < 0.05) and VE (p < 0.05) such that average VO2 and VE during the TT increased with BR, with no difference between normoxia and hypoxia (p ≥ 0.86). We found no effect of supplementation on heart rate, oxygen saturation or muscle oxygenation during the TT. Our results provide new evidence that chronic high-dose NO3- supplementation improves cycling performance of well-trained cyclists in both normoxia and hypoxia.


Assuntos
Beta vulgaris/química , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Hipóxia/metabolismo , Oxigênio/metabolismo , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Humanos , Masculino , Consumo de Oxigênio , Fatores de Tempo , Adulto Jovem
19.
Colloids Surf B Biointerfaces ; 176: 387-393, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30660012

RESUMO

Pectin polysaccharides have significant potential as all-natural, non-toxic "green" coatings that exhibit thermally-cued swelling behavior. Herein, ultra-thin coatings of highly-esterified pectin polysaccharides were cross-linked with calcium chloride (CaCl2) and their swelling in water was investigated with ellipsometry. At low temperatures, the coatings swell to 2-3 times their dry layer thickness. As the temperature is increased, the coatings show a pronounced decrease in swollen thickness, reminiscent of the hydrophilic-hydrophobic transition observed in lower critical solution temperature (LCST) polymers. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy establishes that this transition is driven by dehydration of the esterified galacturonic acid residues along the pectin backbone. By adjusting both the CaCl2 concentration used to crosslink the pectin coatings as well as pH of swelling medium, the pectin coatings could be judiciously tuned for a desired swelling response as a function of temperature. Due to their non-toxic and responsive nature, it was further demonstrated that such coatings could be used in applications to control cell adhesion.


Assuntos
Materiais Revestidos Biocompatíveis/química , Pectinas/química , Polissacarídeos/química , Animais , Reagentes de Ligações Cruzadas/química , Fibroblastos/citologia , Camundongos , Células NIH 3T3 , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Curr Aging Sci ; 11(2): 140-146, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30019655

RESUMO

BACKGROUND: This paper describes a pilot study to assess the feasibility of a novel intervention to improve the management of hypertension among older people in rural South Africa. Older South Africans have the highest rates of uncontrolled hypertension recorded for any country. Notably, South Africa has a widely-available old age grant (pension), which is delivered on a monthly basis to citizens living in rural villages. METHODS: We assessed the feasibility of engaging with older people at the point of pension delivery in the Agincourt sub-district of Mpumalanga Province. This included providing information about hypertension, measuring blood pressure, referral to primary care services, and providing a monthly supply of low sodium salt. We recruited 20 people aged 60 and over to participate in the pilot intervention, which was conducted over three months in two villages. Towards the end of the intervention, we conducted focus groups with study participants and held a meeting with local stakeholders, including the district health office and the state social security agency. RESULTS: The pilot study demonstrated (i) Sustained engagement with the original 20 participants. Of these, 19 continued to participate in the intervention during subsequent monthly pension days. (ii) A high level of acceptance of the low sodium salt product reflected in repeat usage and comments made in the focus groups. (iii) Strong support for the intervention and a willingness to collaborate with local stakeholders. (iv) A perception among participants that symptoms they associated with hypertension had abated. This is supported by blood pressure readings made over the three months of follow-up. CONCLUSION: Though limited in scope, this pilot study provided evidence of the feasibility of the intervention and justification for it to be tested on a larger and more robust basis.


Assuntos
Pressão Sanguínea , Prestação Integrada de Cuidados de Saúde/organização & administração , Dieta Hipossódica , Hipertensão/dietoterapia , Pensões , Serviços de Saúde Rural/organização & administração , Saúde da População Rural , Cloreto de Sódio na Dieta/provisão & distribuição , Fatores Etários , Estudos de Viabilidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Educação de Pacientes como Assunto , Participação do Paciente , Projetos Piloto , Pesquisa Qualitativa , Cloreto de Sódio na Dieta/efeitos adversos , África do Sul/epidemiologia , Fatores de Tempo , Resultado do Tratamento
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