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1.
Int J Nanomedicine ; 15: 7687-7702, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116495

RESUMO

Background: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications. Materials and Methods: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed "all-in-one" FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent. Results: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3-5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs. Conclusion: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.


Assuntos
Háfnio/química , Hipertermia Induzida , Estruturas Metalorgânicas/química , Metaloporfirinas/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Animais , Meios de Contraste/química , Fluorescência , Ácido Fólico/uso terapêutico , Células HeLa , Humanos , Imagem por Ressonância Magnética , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Neoplasias/radioterapia , Técnicas Fotoacústicas , Radioterapia Guiada por Imagem
2.
J Assoc Physicians India ; 68(9): 36-42, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32798344

RESUMO

Objectives: Ideally, the upper reference limit of plasma or serum homocysteine (Hcy) is to be defined from the studies done on individuals with normal cobalamin and folate status. It is difficult to separate the truly healthy (Cobalamin/Folate Replete) individuals from the randomly selected, apparently healthy individuals who are sub-clinically deficient of cobalamin/folate. The present study was aimed at defining the reference values for the serum homocysteine from individuals with normalized cobalamin and folate status. Methods: In our study, 215 patients with cobalamin, folic acid deficiency were treated accordingly till complete restoration of clinical and laboratory abnormalities. The post-therapy serum Hcy values were used as reference values. Results: Post-therapy serum Hcy values 12.56 µmol/L (95th percentile), 11.4 µmol/L (85th percentile), 9.8 µmol/L (67th percentile) were seen. The hyperhomocysteinemia was more visible (17.3% gain in prevalence) in the same patient group if interpreted using the post-therapy Hcy value (11.4 µmol/L) as the cut-off. There was no difference between the genders and age groups in the pre or post-therapy Hcy values. Conclusions: The benefit of the gain in prevalence of disease or the increase in the sensitivity of the test, though small, gets magnified in common diseases and in populous countries. Selection of the individuals is as important as the method or the reagent used in the method when a particular parameter is studied. Repleting the vitamin stores in the confirmed vitamin-deficient patients is more appropriate and easily feasible, since anyway they require treatment, than doing the same on the apparently healthy people. The data thus obtained can be better used as the reference value, for a more meaningful interpretation. The reference range can in turn be used to identify the sub-clinically deficient but asymptomatic people and managed accordingly.


Assuntos
Deficiência de Ácido Fólico , Ácido Fólico/uso terapêutico , Deficiência de Vitamina B 12 , Vitamina B 12/uso terapêutico , Feminino , Deficiência de Ácido Fólico/tratamento farmacológico , Homocisteína , Humanos , Masculino , Valores de Referência , Deficiência de Vitamina B 12/tratamento farmacológico
3.
Med Hypotheses ; 143: 110142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759013

RESUMO

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Ácido Fólico/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/metabolismo , Pandemias , Pneumonia Viral/complicações , Administração por Inalação , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Humanos , Hipertensão Pulmonar/complicações , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Camundongos , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Taquifilaxia
4.
Brasília; s.n; 11 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117979

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Ácido Ursodesoxicólico/uso terapêutico , Imunoglobulinas/uso terapêutico , Prednisolona/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Cloroquina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interferon-alfa/uso terapêutico , Tacrolimo/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Células-Tronco Mesenquimais , Lopinavir/uso terapêutico , Ácido Fólico/uso terapêutico , Meropeném/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Ácido Micofenólico/uso terapêutico
5.
Wilderness Environ Med ; 31(3): 350-353, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32773354

RESUMO

Trioxane is a stable cyclic trimer of formaldehyde. It is an active ingredient in fuel bars for heating prepackaged foods by military and outdoorspeople. Trioxane depolymerizes to formaldehyde in an acidic environment and is further oxidized to formic acid, which causes neurologic and ocular damage. Because it is solid at room temperature, trioxane is a greater potential hazard to children than aqueous formaldehyde. Little information is available regarding the management of ingestion of solid, compressed fuel bars. We present a case of a 19-mo-old male child who ingested an unknown amount of a trioxane fuel bar, with fortunately limited consequences.


Assuntos
Ácido Fólico/uso terapêutico , Formiatos/envenenamento , Envenenamento/tratamento farmacológico , Ingestão de Alimentos , Humanos , Lactente , Masculino , Resultado do Tratamento
6.
Chem Biol Interact ; 327: 109187, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32610055

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is not only one of the pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. IRI after liver transplant occurs due to in major resections and occlusion of vessels, or during the perioperative period, leads to acute liver failure which shows the dynamic process that involves two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury and has an impact on morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) is activated locally in the injured cells by the occurrence of I/R, which plays an essential role in the fate of the damaged tissue. However, a preclinical study explores the protective role of RAAS inhibitor in acute liver injury in a model of inflammation caused by ischemia and reperfusion. In-addition to RAAS blockers in monotherapy does not effectively block the complete pathway. Thus, the present study is designed to explore the effect of combined folic acid with RAAS blockers in combination, produce a synergistic effect. Moreover, in this review, we will describe the understanding of the possible incidence of downregulatory molecular mechanisms associated with renin-angiotensin-aldosterone system and the significance & outcome of the combination of folic acid and RAAS blockers in liver injury due to ischemia/reperfusion.


Assuntos
Ácido Fólico/uso terapêutico , Hepatopatias/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Sinergismo Farmacológico , Homocisteína/metabolismo , Humanos , Hepatopatias/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Ácido Úrico/metabolismo
7.
Int J Nanomedicine ; 15: 3433-3445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523342

RESUMO

Background: Reconstituted lipoproteins (rLips) based on endogenous lipid nanostructures has been increasingly regarded as an excellent and promising antitumor drug delivery. However, some problems relating to the main component, apolipoprotein, for instance, rare source, unaffordable price, and low specificity of relevant receptor expression, become chief obstacles to its broad development and application. Purpose: The primary aim of this study is to develop biomimetic rLips by utilizing folic acid (FA)-modified bovine serum albumin (BSA) as a replacement for apolipoprotein and demonstrate its tumor targeting and antitumor efficacy. Methods: The amino groups of BSA were covalently conjugated with FA through the amide reaction. PTX-loaded nanostructured lipid carrier (termed as P-NLC) consisting of phospholipid, cholesteryl ester, triglyceride and cholesterol was prepared by the emulsification-evaporation method and utilized as the lipid core. FA-modified BSA (FA-BSA) was characterized for the protein substitute degree and attached with NLC by incubation-insert method to form the lipoprotein-mimic nanocomplex (termed as PFB-rLips). The morphology of nanoparticles was observed under transmission electron microscopy (TEM), and the particle size and zeta potential were determined using dynamic light scattering. In vitro release behavior of PTX from PFB-rLips was investigated with the dialysis method. Hemolysis tests were conducted to evaluate the biosecurity of PFB-rLips. Cell uptake and cytotoxicity assays were performed on human hepatocytes (LO2) and human hepatoma cells (HepG2). Tumor targeting was assessed using in vivo imaging system in H22 tumor-bearing mice model. Antitumor efficacy in vivo was investigated and compared between Taxol® (paclitaxel) formulation and PTX-incorporated nanoparticles in the same tumor model. Results: A fixed molar ratio 50:1 of FA to BSA was chosen as the optimal input ratio based on the balance between appropriate degree of protein substitution and amphiphilicity of FA-BSA. The morphology of FB-rLips exhibited as a homogeneous spherical structure featured by lipid cores surrounded with a cloudy protein shell observed under TEM. The particle size, zeta potential and encapsulation efficiency were 174.6±3.2 nm, -17.26±0.9 mV and 82.2±2.4%, respectively. In vitro release behavior of PTX from PFB-rLips was slow and sustained. The uptake of FB-rLips was much higher in HepG2 cells than in LO2 cells. Furthermore, the uptake of FB-rLips was significantly higher than that of rLips without FA involved (termed as B-rLips) and NLC in HepG2 cells. Hemolysis and cytotoxicity assays showed good biocompatibility of FB-rLips. The internalization mechanism of FB-rLips mainly depended on clathrin-mediated and caveolin-mediated endocytosis coupling with energy consumption, and FA receptors expressed on tumor cells played a critical role in cellular uptake process. CCK-8 studies demonstrated that PFB-rLips exhibited significantly better tumor killing ability than Taxol® (paclitaxel) formulation in vitro. Moreover, FB-rLips produced more excellent tumor-targeting properties than NLC through in vivo imaging assays. On the basis of this, PTX-loaded FB-rLips also performed more remarkable anticancer activity than other therapy groups in H22 tumor-bearing mice. Conclusion: FB-rLips would serve as a potential nanocarrier for improving tumor-targeting and therapeutic efficacy while reducing the side effects on normal tissues and organs.


Assuntos
Portadores de Fármacos/química , Ácido Fólico/uso terapêutico , Lipoproteínas/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Ácido Fólico/síntese química , Ácido Fólico/química , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Nanopartículas/ultraestrutura , Neoplasias/patologia , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Tamanho da Partícula , Coelhos , Soroalbumina Bovina/química , Eletricidade Estática
8.
PLoS One ; 15(5): e0232625, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365114

RESUMO

INTRODUCTION: Anemia during pregnancy has a significant adverse effect on both the mother and fetus. Iron and folic acid supplementation (IFAS) is the feasible and cost effective strategy to control and prevent anemia in pregnancy. However, the success of this strategy is suboptimal due to poor maternal adherences to the regimen. The aim of this study was to assess prevalence of anemia, rate of adherence to IFAS and associated factors among pregnant women at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. METHOD: Institution based cross sectional study was conducted among 250 pregnant women who were selected using systematic random sampling from antenatal care clinic (ANC) attendants of TASH. Data was collected through interview and medical chart review by using structured questionnaire. The data was analyzed by SPSS v.24. Binary logistic regression was used to identify the associated factors for IFAS and P < 0.05 was used to declare the association. RESULTS: The prevalence of anemia was 4.8% and half of the study participants were knowledgeable about anemia. The rate of adherence to IFAS was 63.6%. Forgetfulness and fear of side effect were the commonest reasons for poor adherence to IFAS. Gestational age at first ANC visit and educational level were significantly associated with adherence to IFAS. Thus, pregnant women who started their ANC follow up at first trimester (AOR = 1.87, 95% CI (1.18-3.36)) and education level of college and above (AOR = 4.236, 95% CI (1.35-13.25)) and completed secondary education (AOR = 4.09, 95% CI (1.39-12.02)) were more likely to be adherent to IFAS compared with their comparators. CONCLUSION: Even though anemia prevalence was very low among the study participants, adherence to IFAS was still a challenge during pregnancy. Therefore, counseling about IFAS and anemia prevention and promoting the benefits of early ANC visit are recommended to improve adherence to IFAS.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Ferro/uso terapêutico , Complicações Hematológicas na Gravidez/epidemiologia , Adulto , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Cooperação do Paciente , Educação de Pacientes como Assunto , Gravidez , Cuidado Pré-Natal , Prevalência , Análise de Regressão , Classe Social , Inquéritos e Questionários , Adulto Jovem
9.
Cochrane Database Syst Rev ; 5: CD011033, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32364620

RESUMO

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.


Assuntos
Inibidores da Agregação de Plaquetas/uso terapêutico , Tromboangiite Obliterante/tratamento farmacológico , Adulto , Alprostadil/uso terapêutico , Amputação/estatística & dados numéricos , Aspirina/uso terapêutico , Epoprostenol/análogos & derivados , Epoprostenol/uso terapêutico , Ácido Fólico/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Iloprosta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Placebos/uso terapêutico , Prostaglandinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboangiite Obliterante/cirurgia , Úlcera/tratamento farmacológico
10.
Anaesthesia ; 75(8): 1039-1049, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32342498

RESUMO

In patients with pre-operative anaemia undergoing cardiac surgery, combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12 and oral folic acid reduces allogeneic blood product transfusions. It is unclear if certain types of anaemia particularly benefit from this treatment. We performed a post-hoc analysis of anaemic patients from a randomised trial on the 'Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery'. We used linear regression analyses to examine the efficacy of a combination anaemia treatment compared with placebo on the following deficiencies, each representing a part of the combination treatment: ferritin and transferrin saturation; endogenous erythropoietin; holotranscobalamine; and folic acid in erythrocytes. Efficacy was defined as change in reticulocyte count from baseline to the first, third and fifth postoperative days and represented erythropoietic activity in the immediate peri-operative recovery phase. In all 253 anaemic patients, iron deficiency was the most common cause of anaemia. Treatment significantly increased reticulocyte count in all regression analyses on postoperative days 1, 3 and 5 (all p < 0.001). Baseline ferritin and endogenous erythropoietin were negatively associated with change in reticulocyte count on postoperative day 5, with an unstandardised regression coefficient B of -0.08 (95%CI -0.14 to -0.02) and -0.14 (95%CI -0.23 to -0.06), respectively. Quadruple anaemia treatment was effective regardless of the cause of anaemia and its effect manifested early in the peri-operative recovery phase. The more pronounced a deficiency was, the stronger the subsequent boost to erythropoiesis may have been.


Assuntos
Anemia/tratamento farmacológico , Cuidados Pré-Operatórios/métodos , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/tratamento farmacológico , Transfusão de Sangue/estatística & dados numéricos , Procedimentos Cirúrgicos Cardíacos/métodos , Método Duplo-Cego , Quimioterapia Combinada , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/uso terapêutico , Hematínicos/administração & dosagem , Hematínicos/uso terapêutico , Humanos , Ferro/administração & dosagem , Ferro/uso terapêutico , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Contagem de Reticulócitos , Vitamina B 12/administração & dosagem , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico
11.
BMC Public Health ; 20(1): 457, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252698

RESUMO

BACKGROUND: To reduce the prevalence of anemia, the Indian government recommends daily iron and folic acid supplements (iron supplements) for pregnant women and weekly iron supplements for adolescents and all women of reproductive age. The government has distributed free iron supplements to adolescents and pregnant women for over four decades. However, initial uptake and adherence remain inadequate and non-pregnant women of reproductive age are largely ignored. The aim of this study is to examine the multilevel barriers to iron supplement use and to subsequently identify promising areas to intervene. METHODS: We conducted a qualitative study in the state of Odisha, India. Data collection included key informant interviews, focus group discussions with women, husbands, and mothers-in-law, and direct observations in health centers, pharmacies and village health and nutrition days. RESULTS: We found that at the individual level, participants knew that iron supplements prevent anemia but underestimated anemia prevalence and risk in their community. Participants also believed that taking too many iron supplements during pregnancy would "make your baby big" causing a painful birth and a costly cesarean section. At the interpersonal level, mothers-in-law were not supportive of their daughters-in-law taking regular iron supplements during pregnancy but husbands were more supportive. At the community level, participants reported that only pregnant women and adolescents are taking iron supplements, ignoring non-pregnant women altogether. Unequal gender norms are also an upstream barrier for non-pregnant women to prioritize their health to obtain iron supplements. At the policy level, frontline health workers distribute iron supplements to pregnant women only and do not follow up on adherence. CONCLUSIONS: Interventions should address multiple barriers to iron supplement use along the socio-ecological model. They should also be tailored to a woman's reproductive life course stage: adolescents, pregnancy, and non-pregnant women of reproductive age because social norms and available services differ between the subpopulations.


Assuntos
Anemia/prevenção & controle , Suplementos Nutricionais/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Ferro/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adolescente , Adulto , Anemia/epidemiologia , Anemia/psicologia , Feminino , Grupos Focais , Ácido Fólico/uso terapêutico , Humanos , Índia/epidemiologia , Ferro/deficiência , Masculino , Análise Multinível , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/prevenção & controle , Complicações Hematológicas na Gravidez/psicologia , Cuidado Pré-Natal/psicologia , Prevalência , Pesquisa Qualitativa , Adulto Jovem
12.
Curr Urol Rep ; 21(3): 15, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32185555

RESUMO

PURPOSE OF REVIEW: To discuss the overall and latest observations of the effect of diet, lifestyle, supplements, and some prescription heart healthy medications for prostate cancer prevention. RECENT FINDINGS: The concept of maximizing heart health to prevent aggressive prostate cancer continues to be solidified with the addition of more prospective observational and randomized controlled trial data. Heart healthy is prostate healthy, and heart unhealthy is prostate unhealthy. The primary goal of reducing the risk of all-cause and cardiovascular disease (CVD) morbidity and mortality also coincides with maximizing prostate cancer prevention. The obesity epidemic in children and adults along with recent diverse research has only strengthened the nexus between heart and prostate health. Greater dietary adherence toward a variety of healthy foods is associated with a graded improved probability of CVD and potentially aggressive cancer risk reduction. Preventing prostate cancer via dietary supplements should encourage a "first do no harm," or less is more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer. Supplements to reduce side effects of some cancer treatments appear to have more encouraging data. A discussion of quality (QC) before utilizing any pill also requires attention. Medications or interventions that potentially improve heart health including statins, aspirin, and metformin (S.A.M.), specific beta-blocker medications, and even preventive vaccines are in general generic, low-cost, "natural," and should continue to garner research interest. A watershed moment in medical education has arrived where the past perception of a diverse number of trees seemingly separated by vast distances, in reality, now appear to exist within the same forest.


Assuntos
Dieta , Suplementos Nutricionais/normas , Estilo de Vida , Neoplasias da Próstata/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais/efeitos adversos , Óleos de Peixe/uso terapêutico , Ácido Fólico/uso terapêutico , Alimentos/normas , Nível de Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Medicamentos sob Prescrição/normas , Controle de Qualidade , Comportamento de Redução do Risco , Vitamina B 12/uso terapêutico
14.
Neurology ; 94(11): e1126-e1136, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-31932513

RESUMO

OBJECTIVE: We evaluated the interaction of serum folate and vitamin B12 with methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke. METHODS: A total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months. RESULTS: Median values of folate and B12 concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B12 or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with MTHFR 677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B12 below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in MTHFR 677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B12 levels above the median (HR, 0.28; 95% CI, 0.10-0.75). CONCLUSIONS: The risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B12. Effect of folic acid treatment was greatest in patients with low folate and B12 with the CC genotype, and with high folate and B12 with the TT genotype.


Assuntos
Ácido Fólico/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/prevenção & controle , Idoso , Anti-Hipertensivos/uso terapêutico , Método Duplo-Cego , Enalapril/uso terapêutico , Feminino , Ácido Fólico/sangue , Genótipo , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Vitamina B 12/sangue
15.
JAMA ; 323(1): 35-48, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910279

RESUMO

Importance: Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth. Objective: To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. Design, Setting, and Participants: The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019. Interventions: Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. Main Outcomes and Measures: The co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. Results: Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]). Conclusions and Relevance: Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility. Trial Registration: ClinicalTrials.gov Identifier: NCT01857310.


Assuntos
Suplementos Nutricionais , Ácido Fólico/farmacologia , Infertilidade Masculina/tratamento farmacológico , Sêmen/efeitos dos fármacos , Zinco/farmacologia , Adolescente , Adulto , Fragmentação do DNA/efeitos dos fármacos , Suplementos Nutricionais/efeitos adversos , Feminino , Fertilização In Vitro , Ácido Fólico/efeitos adversos , Ácido Fólico/uso terapêutico , Humanos , Nascimento Vivo , Masculino , Pessoa de Meia-Idade , Análise do Sêmen , Contagem de Espermatozoides , Falha de Tratamento , Adulto Jovem , Zinco/efeitos adversos , Zinco/uso terapêutico
16.
PLoS One ; 15(1): e0227090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910215

RESUMO

BACKGROUND: Iron-folic acid supplementation during pregnancy is among the very effective interventions to prevent iron deficiency anemia, low birth weight, and prematurity. There is a need of having recent studies on adherence to the supplement that consider the very recent interventions targeted to scale up the use of iron-folic acid (IFA) supplement. Therefore we sought to assess adherence to IFA supplement and its associated factors among antenatal care attending pregnant mothers in governmental health institutions of Adwa town. METHODS: Institution-based cross-sectional study was conducted among 629 antenatal care attending pregnant mothers. Systematic random sampling method was used to select the study subjects. Data were collected through face-to-face interview and chart-review. Bivariable and multivariable binary logistic regression was computed. Variables with P-value <0.05 were considered statistically significant at 95% confidence interval (CI). RESULT: Only 40.9% (95%CI: 37.0%- 44.7%) of participants were adherent (took four or more tablets per week). Women in the age group of 25-29 years [AOR: 2.22(1.21-4.07)] had increased odds of adherence as compared to those in the age group ≥ 35 years. Women who received nutrition counseling [AOR: 4.12(2.12-8.03)] and partner support [AOR: 2.23 (1.42-3.49)] had increased odds of adherence as compared to those who didn't receive nutrition counseling and partner support respectively. Similarly, women who had satisfactory knowledge on IFA supplement (AOR: 2.16(1.37-3.40)) had increased odds of adherence as compared to those who didn't have satisfactory knowledge on IFA supplement. CONCLUSION: Adherence to the supplement was low. Efforts shall be done to improve awareness of pregnant mothers about IFA supplement through targeted nutrition counseling that includes the engagement of a partner.


Assuntos
Ácido Fólico/administração & dosagem , Ferro/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Cuidado Pré-Natal/normas , Oligoelementos/administração & dosagem , Vitaminas/administração & dosagem , Adulto , Anemia/prevenção & controle , Uso de Medicamentos/estatística & dados numéricos , Etiópia , Feminino , Ácido Fólico/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Hospitais Públicos/estatística & dados numéricos , Humanos , Ferro/uso terapêutico , Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Oligoelementos/uso terapêutico , Vitaminas/uso terapêutico
17.
PLoS One ; 15(1): e0227351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923240

RESUMO

INTRODUCTION: Iron and Folic Acid Supplementation (IFAS) is an essential and affordable intervention strategy for prevention of anaemia during pregnancy. The supplements are currently provided for free to pregnant women in Kenya during antenatal care (ANC), but compliance remains low over the years. There is need for diversification of IFAS programme implementation by exploring other distribution channels to complement existing antenatal distribution and ensure consistent access to IFAS supplements. OBJECTIVES: To determine the effect of a community-based approach of IFAS distribution on compliance and assess side-effects experienced and their mitigation by pregnant women in Kiambu County. METHODOLOGY: A pretest-posttest quasi-experimental study design was used, consisting of an intervention and a control group, among 340 pregnant women 15-49 years, in five health facilities in Lari Sub-County in Kiambu County, between June 2016 and March 2017. Community health volunteers provided IFAS supplements, counselling and weekly follow-up to pregnant women in the intervention group while the control group followed standard practice from health facilities. Baseline and endline data were collected during antenatal care and compared. Quantitative data was analyzed using STATA version 14. Analysis of effect of intervention was done using Difference-In-Difference regression approach. RESULTS: Levels of compliance increased by 8% in intervention group and 6% in control group. There was increased awareness of IFAS side-effects across groups. The intervention group reported experiencing less side-effects and were better able to manage them compared to the control group. CONCLUSION: Implementation a community-based approach improved maternal compliance with IFAS, awareness of IFAS side effects and their management, with better improvement being recorded in the intervention group. Hence, there is need to integrate community-based approach with antenatal distribution of IFAS to improve supplementation.


Assuntos
Anemia/prevenção & controle , Ácido Fólico/uso terapêutico , Ferro/uso terapêutico , Gestantes , Adolescente , Adulto , Estudos de Casos e Controles , Serviços de Saúde Comunitária/normas , Suplementos Nutricionais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Quênia , Pessoa de Meia-Idade , Cooperação do Paciente , Gravidez , Cuidado Pré-Natal , Adulto Jovem
18.
PLoS One ; 15(1): e0228399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995624

RESUMO

Sickle cell disease (SCD) consists of a group of hemoglobinopathies in which individuals present highly variable clinical manifestations. Sickle cell anemia (SCA) is the most severe form, while SC hemoglobinopathy (HbSC) is thought to be milder. Thus, we investigated the clinical manifestations and laboratory parameters by comparing each SCD genotype. We designed a cross-sectional study including 126 SCA individuals and 55 HbSC individuals in steady-state. Hematological, biochemical and inflammatory characterization was performed as well as investigation of previous history of clinical events. SCA patients exhibited most prominent anemia, hemolysis, leukocytosis and inflammation, whereas HbSC patients had increased lipid determinations. The main cause of hospitalization was pain crises on both genotypes. Vaso-occlusive events and pain crises were associated with hematological, inflammatory and anemia biomarkers on both groups. Cluster analysis reveals hematological, inflammatory, hemolytic, endothelial dysfunction and anemia biomarkers in HbSC disease as well as SCA. The results found herein corroborate with previous studies suggesting that SCA and HbSC, although may be similar from the genetic point of view, exhibit different clinical manifestations and laboratory alterations which are useful to monitor the clinical course of each genotype.


Assuntos
Anemia Falciforme/metabolismo , Biomarcadores/análise , Hemoglobina Falciforme/genética , Adolescente , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/genética , Criança , Estudos Transversais , Feminino , Ácido Fólico/uso terapêutico , Genótipo , Doença da Hemoglobina SC/tratamento farmacológico , Doença da Hemoglobina SC/genética , Doença da Hemoglobina SC/metabolismo , Humanos , Hidroxiureia/uso terapêutico , Masculino
19.
Yakugaku Zasshi ; 140(1): 15-22, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31902879

RESUMO

The development of serious lung diseases, such as pulmonary fibrosis, is associated with several drugs. A recent study has shown that the epithelial-mesenchymal transition (EMT) plays an essential role in the development of pulmonary fibrosis. However, the mechanisms underlying drug-induced EMT in alveolar epithelial cells have not been characterized. The present study showed that methotrexate (MTX), a drug known to cause lung injury, induced EMT-like phenotypic changes in an A549 cell model of the alveolar epithelium. We also found that the transforming growth factor (TGF)-ß1-mediated signaling pathway was associated with MTX-induced EMT. In addition, our results showed that certain secreted factors and microRNAs, a class of small noncoding RNAs, may be involved in MTX-induced EMT. The effects of COA-Cl, a novel synthetic small molecule, on TGF-ß1-induced EMT were evaluated to determine the therapeutic potential of COA-Cl against drug-induced lung injury. COA-Cl significantly suppressed TGF-ß1-induced EMT-like phenotypic changes, as evidenced by the inhibition of EMT-related transcription factors. Furthermore, MTX-induced EMT was completely suppressed by co-treatment with folic acid. Thus, these compounds may be promising therapeutic agents against drug-induced lung injury. In conclusion, the present study elucidated mechanisms underlying drug-induced EMT and highlighted a potential novel therapeutic approach to drug-induced lung diseases.


Assuntos
Lesão Pulmonar/induzido quimicamente , Metotrexato/efeitos adversos , Adenosina/análogos & derivados , Adenosina/farmacologia , Adenosina/uso terapêutico , Animais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/uso terapêutico , Humanos , Lesão Pulmonar/tratamento farmacológico , MicroRNAs , Terapia de Alvo Molecular , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1/fisiologia
20.
J Knee Surg ; 33(1): 34-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30620987

RESUMO

Despite the evolution of blood management protocols, total knee arthroplasty (TKA) occasionally requires allogeneic blood transfusion. This poses a particular challenge for Jehovah's Witnesses (JW) who believe that the Bible strictly prohibits the use of blood products. The aim of this study was to compare JW and a matched-control cohort of non-JW candidates undergoing TKA to assess the safety using modern blood management protocols. Fifty-five JW patients (63 knees) who underwent TKA at our institution between 2005 and 2017 were matched to 63 non-JW patients (63 knees). Patient demographics, intraoperative details, and postoperative complications including in-hospital complications, revisions, and 90-day readmissions were collected and compared between the groups. Additionally, subgroup analysis was performed comparing JW patients who were administered tranexamic acid (TXA) between the two groups. Baseline demographics did not vary significantly between the study cohorts. The mean follow-up was 3.1 years in both the JW and non-JW cohorts. Postoperative complications, including in-hospital complications (7.9 vs. 4.8%; p = 0.47), revision TKA (1.6 vs. 1.6%; p = 1.00), and 90-day readmission (1.6 vs. 4.8%; p = 0.31) were not significantly different between the JW and non-JW groups. Subgroup analysis demonstrated JW patients who received TXA had a significantly lower decline in postoperative hemoglobin (Hgb) (8.6 vs. 14.0%; p < 0.01). At a follow-up of up to 12 years, JW patients who underwent TKA have outcomes equivalent to non-JW patients without the need for transfusion. Our findings support that surgeons are more likely to optimize JW patients preoperatively with iron and folate supplementation. Despite these variations in preoperative optimization efforts, no significant difference with regard to Hgb or hematocrit levels was demonstrated. Level of evidence is III, retrospective observational study.


Assuntos
Anemia/terapia , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Testemunhas de Jeová , Hemorragia Pós-Operatória/terapia , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/métodos , Epoetina alfa/uso terapêutico , Feminino , Ácido Fólico/uso terapêutico , Hematínicos/uso terapêutico , Hemoglobinas/análise , Hemostasia Cirúrgica , Humanos , Compostos de Ferro/uso terapêutico , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Cuidados Pré-Operatórios , Estudos Retrospectivos , Ácido Tranexâmico/uso terapêutico , Resultado do Tratamento
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