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1.
Nutrients ; 13(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572045

RESUMO

BACKGROUND: Zinc is an essential micronutrient that impacts host-pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. METHODS: We ran an observational cohort study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel, we have studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) replication in the Vero E6 cell line modifying zinc concentrations. FINDINGS: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dL at admission correlated with worse clinical presentation, longer time to reach stability, and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV-2 infected cells. INTERPRETATION: Low SZC is a risk factor that determines COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency.


Assuntos
/sangue , Zinco/sangue , Idoso , Animais , Sobrevivência Celular , Chlorocebus aethiops , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Vero , Zinco/administração & dosagem , Zinco/farmacologia
2.
PLoS Negl Trop Dis ; 15(1): e0008895, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395417

RESUMO

A wide variety of symptoms is associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and these symptoms can overlap with other conditions and diseases. Knowing the distribution of symptoms across diseases and individuals can support clinical actions on timelines shorter than those for drug and vaccine development. Here, we focus on zinc deficiency symptoms, symptom overlap with other conditions, as well as zinc effects on immune health and mechanistic zinc deficiency risk groups. There are well-studied beneficial effects of zinc on the immune system including a decreased susceptibility to and improved clinical outcomes for infectious pathogens including multiple viruses. Zinc is also an anti-inflammatory and anti-oxidative stress agent, relevant to some severe Coronavirus Disease 2019 (COVID-19) symptoms. Unfortunately, zinc deficiency is common worldwide and not exclusive to the developing world. Lifestyle choices and preexisting conditions alone can result in zinc deficiency, and we compile zinc risk groups based on a review of the literature. It is also important to distinguish chronic zinc deficiency from deficiency acquired upon viral infection and immune response and their different supplementation strategies. Zinc is being considered as prophylactic or adjunct therapy for COVID-19, with 12 clinical trials underway, highlighting the relevance of this trace element for global pandemics. Using the example of zinc, we show that there is a critical need for a deeper understanding of essential trace elements in human health, and the resulting deficiency symptoms and their overlap with other conditions. This knowledge will directly support human immune health for decreasing susceptibility, shortening illness duration, and preventing progression to severe cases in the current and future pandemics.


Assuntos
/tratamento farmacológico , Zinco/administração & dosagem , Zinco/deficiência , Anti-Inflamatórios/farmacologia , /virologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Fatores de Risco , /isolamento & purificação
3.
Avian Dis ; 64(4): 451-456, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347551

RESUMO

Major histocompatibility complex (MHC) congenic chicken lines have been used as a model to study infectious bronchitis virus (IBV) immune responses in chickens. Zinc (Zn) and manganese (Mn) are trace minerals that act as enzyme cofactors in cellular reactions. In addition, Zn is an important modulator of immune responses, especially in the respiratory tract. Zinc and Zn + Mn amino acid complex supplements were tested to alleviate the effects of an IBV challenge using relatively resistant and susceptible MHC congenic chicken lines. Prior to the challenge with IBV, the amino acid-bound supplements induced better weight gain in the IBV-resistant chicken line (331/B2) compared to the birds fed with the sulfate-delivered supplements. No body weight differences were detected between IBV-challenged and unchallenged 331/B2 birds supplemented with Zn in amino acid complex. A reduction of respiratory signs was observed in 335/B19 birds fed with the diet supplemented with Zn in amino acid complexes at 4 dpi. Compared to the sulfate-bound trace minerals, 331/B2 chickens fed with the amino acid-bound supplements presented milder clinical sign trends at 6 dpi and less severe airsacculitis at 14 dpi. The total antibody response in serum in 331/B2 birds fed with the amino acid-bound Zn ration was the highest among all groups tested. Both amino acid-delivered trace mineral supplements induced a slightly higher antibody response than the sulfate-bound ration in both chicken lines. This experiment provides insights into the effect of Zn and Mn on the immunity of chickens with known different susceptibilities to IBV.


Assuntos
Infecções por Coronavirus/veterinária , Suplementos Nutricionais , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas/dietoterapia , Aminoácidos/administração & dosagem , Ração Animal/análise , Animais , Animais Congênicos , Anticorpos Antivirais/sangue , Galinhas/genética , Galinhas/imunologia , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/veterinária , Haplótipos , Vírus da Bronquite Infecciosa/imunologia , Complexo Principal de Histocompatibilidade , Manganês/administração & dosagem , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/imunologia , Zinco/administração & dosagem
4.
Trials ; 21(1): 892, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109252

RESUMO

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Ácido Ascórbico , Betacoronavirus , Infecções por Coronavirus , Medicina Ayurvédica/métodos , Pandemias , Pneumonia Viral , Zinco , Adulto , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Infecções Assintomáticas/terapia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Suplementos Nutricionais , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Índia , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Carga Viral/métodos , Zinco/administração & dosagem , Zinco/efeitos adversos
5.
N Engl J Med ; 383(13): 1231-1241, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32966722

RESUMO

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).


Assuntos
Antidiarreicos/administração & dosagem , Diarreia/tratamento farmacológico , Zinco/administração & dosagem , Antidiarreicos/efeitos adversos , Antidiarreicos/sangue , Pré-Escolar , Diarreia Infantil/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Adesão à Medicação , Vômito/induzido quimicamente , Vômito/epidemiologia , Zinco/efeitos adversos , Zinco/sangue
6.
Biomolecules ; 10(8)2020 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-32784855

RESUMO

Zinc therapy is normally utilized for treatment of Wilson disease (WD), an inherited condition that is characterized by increased levels of non-ceruloplasmin bound ('free') copper in serum and urine. A subset of patients with Alzheimer's disease (AD) or its prodromal form, known as Mild Cognitive Impairment (MCI), fail to maintain a normal copper metabolic balance and exhibit higher than normal values of non-ceruloplasmin copper. Zinc's action mechanism involves the induction of intestinal cell metallothionein, which blocks copper absorption from the intestinal tract, thus restoring physiological levels of non-ceruloplasmin copper in the body. On this basis, it is employed in WD. Zinc therapy has shown potential beneficial effects in preliminary AD clinical trials, even though the studies have missed their primary endpoints, since they have study design and other important weaknesses. Nevertheless, in the studied AD patients, zinc effectively decreased non-ceruloplasmin copper levels and showed potential for improved cognitive performances with no major side effects. This review discusses zinc therapy safety and the potential therapeutic effects that might be expected on a subset of individuals showing both cognitive complaints and signs of copper imbalance.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Cobre/metabolismo , Zinco/uso terapêutico , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Ceruloplasmina/metabolismo , Disfunção Cognitiva/enzimologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Humanos , Zinco/administração & dosagem , Zinco/efeitos adversos , Zinco/metabolismo
7.
Tohoku J Exp Med ; 251(3): 175-181, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641644

RESUMO

The novel coronavirus disease 2019 (COVID-19) is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Millions around the world are wondering, if there is anything that could be done, other than maintaining high personal hygiene, and be vigilant of the symptoms, to reduce the spread of the disease and chances of getting infected, or at least to lessen the burden of the disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this article, I will briefly discuss, why keeping adequate zinc balance might enhance the host response and be protective of viral infections.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Zinco/fisiologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Fatores Etários , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Suplementos Nutricionais , Resistência à Doença/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Sistema Imunitário/efeitos dos fármacos , Micronutrientes/fisiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Replicação Viral/efeitos dos fármacos , Zinco/administração & dosagem , Zinco/deficiência , Zinco/farmacologia
8.
Am J Trop Med Hyg ; 103(4): 1416-1426, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32618258

RESUMO

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.


Assuntos
Biomarcadores/análise , Diarreia/tratamento farmacológico , Fezes/química , Zinco/administração & dosagem , Desenvolvimento Infantil/efeitos dos fármacos , Saúde da Criança , Diarreia/epidemiologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Lactente , Laos/epidemiologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/efeitos adversos , Micronutrientes/uso terapêutico , Neopterina/análise , Peroxidase/análise , Zinco/efeitos adversos , Zinco/uso terapêutico
9.
Cochrane Database Syst Rev ; 7: CD008037, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32671834

RESUMO

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, would be a significant therapeutic advance. This is an update of a previously published review. OBJECTIVES: To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis. SEARCH METHODS: We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings. Date of most recent search: 16 January 2020. We also searched MEDLINE (all years) on 14 February 2019 and ongoing trials registers on 06 April 2020. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two of the authors independently assessed and extracted data from identified trials. MAIN RESULTS: We identified 42 trials of which eight (350 participants) that examined antibiotic adjuvant therapies are included. Two further trials are ongoing and five are awaiting classification. The included trials assessed ß-carotene (one trial, 24 participants), garlic (one trial, 34 participants), KB001-A (a monoclonal antibody) (two trials, 196 participants), nitric oxide (two trials, 30 participants) and zinc supplementation (two trials, 66 participants). The zinc trials recruited children only, whereas the remaining trials recruited both adults and children. Three trials were located in Europe, one in Asia and four in the USA. Three of the interventions measured our primary outcome of pulmonary exacerbations (ß-carotene, mean difference (MD) -8.00 (95% confidence interval (CI) -18.78 to 2.78); KB001-A, risk ratio (RR) 0.25 (95% CI 0.03 to 2.40); zinc supplementation, RR 1.85 (95% CI 0.65 to 5.26). ß-carotene and KB001-A may make little or no difference to the number of exacerbations experienced (low-quality evidence); whereas, given the moderate-quality evidence we found that zinc probably makes no difference to this outcome. Respiratory function was measured in all of the included trials. ß-carotene and nitric oxide may make little or no difference to forced expiratory volume in one second (FEV1) (low-quality evidence), whilst garlic probably makes little or no difference to FEV1 (moderate-quality evidence). It is uncertain whether zinc or KB001-A improve FEV1 as the certainty of this evidence is very low. Few adverse events were seen across all of the different interventions and the adverse events that were reported were mild or not treatment-related (quality of the evidence ranged from very low to moderate). One of the trials (169 participants) comparing KB001-A and placebo, reported on the time to the next course of antibiotics; results showed there is probably no difference between groups, HR 1.00 (95% CI 0.69 to 1.45) (moderate-quality evidence). Quality of life was only reported in the two KB001-A trials, which demonstrated that there may be little or no difference between KB001-A and placebo (low-quality evidence). Sputum microbiology was measured and reported for the trials of KB001-A and nitric oxide (four trials). There was very low-quality evidence of a numerical reduction in Pseudomonas aeruginosa density with KB001-A, but it was not significant. The two trials looking at the effects of nitric oxide reported significant reductions in Staphylococcus aureus and near-significant reductions in Pseudomonas aeruginosa, but the quality of this evidence is again very low. AUTHORS' CONCLUSIONS: We could not identify an antibiotic adjuvant therapy that we could recommend for treating of lung infection in people with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Fibrose Cística/complicações , Pneumopatias/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Infecções Bacterianas/microbiologia , Quimioterapia Adjuvante , Criança , Progressão da Doença , Alho , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Pneumopatias/microbiologia , Óxido Nítrico/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitaminas/uso terapêutico , Adulto Jovem , Zinco/administração & dosagem , beta Caroteno/uso terapêutico
10.
Clin Nutr ESPEN ; 38: 65-66, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32690179

RESUMO

BACKGROUND & AIMS: The COVID-19 infection can lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affecting patients aged 60 and older. Preliminary data suggest that the nutritional status can change the course of the infection, and on the matter, zinc is crucial for growth, development, and the maintenance of immune function. In the absence of treatment for this virus, there is an urgent need to find alternative methods that can contribute to control of disease. The aim of this paper is to establish the relation between zinc and COVID-19. METHODS AND RESULTS: From the prior scientific knowledge, we have performed a review of the literature and examine the role of zinc in immune function in the infection by COVID-19. Our findings are that the zinc as an anti-inflammatory agent may help to optimize immune function and reduce the risk of infection. CONCLUSIONS: Zinc supplementation can be a useful strategy to reduce the global burden of infection in the elderly, there is a need the increased reporting to improve our understanding of COVID-19 and the care of affected patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Imunidade/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Oligoelementos/administração & dosagem , Zinco/administração & dosagem , Idoso , Infecções por Coronavirus/imunologia , Feminino , Humanos , Fatores Imunológicos/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Oligoelementos/imunologia , Zinco/imunologia
11.
Buenos Aires; IECS; 28 jul. 2020.
Não convencional em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-1119361

RESUMO

CONTEXTO CLÍNICO: La enfermedad por el Coronavirus 2019 (COVID-19), por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos por un nuevo Coronovirus identificado con la sigla SARS-CoV-2. TECNOLOGÍA: La vitamina C o ácido ascórbico es una vitamina soluble en agua con una función conocida sobre la síntesis de colágeno en tejidos conectivos y actúa como antioxidante. La vitamina D no solo es un nutriente sino también una hormona, que puede sintetizarse en nuestro cuerpo con la ayuda de la luz solar. El zinc es un oligoelemento dietético y es importante para el mantenimiento y el desarrollo de las células inmunes del sistema inmunitario innato y adaptativo. La deficiencia de Zinc resulta en la disfunción de la inmunidad humoral y mediada por células y aumenta la susceptibilidad a enfermedades infecciosas. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de suplementos vitamínicos (Vit. C, D) y Zinc en la infección por COVID-19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y recomendaciones de diferentes organizaciones de salud. RESULTADOS: Se incluyeron una RS con MA, un protocolo de RS, un estudio observacional retrospectivo y ocho recomendaciones de sociedades científicas. No se hallaron estudios que evalúen la suplementación con vitaminas C y D para la prevención o tratamiento de la infección por COVID-19. Para Zinc, se halló un solo estudio que lo utiliza combinado con tratamientos discontinuados para esta patología por alertas en su seguridad. CONCLUSIONES: No hallaron estudios que evalúen la suplementación con las vitaminas C y D, solas o combinadas con otros tratamientos, en la prevención o tratamiento de la infección por COVID-19. Tampoco se encontraron estudios preventivos que evaluén el uso de Zinc. En el caso de su uso terapéutico, evidencia de muy baja calidad no permite determinar los efectos de la suplementación con Zinc en pacientes hospitalizados por COVID-19. Aunque se desconoce el efecto preventivo en relación al COVID-19, se halló evidencia de alta calidad de estudios realizados durante la era pre- COVID-19 que muestra que, en población general, la suplementación con vitamina D reduce el riesgo de infecciones respiratorias agudas. La incertidumbre actual podría reducirse a corto o mediano plazo debido a que se encuentran en curso aproximadamente 90 estudios que evaluarán el efecto de la administración C y D, y Zinc, solas o en combinación con otros tratamientos, para la prevención o tratamiento de la infección por COVID-19.


Assuntos
Humanos , Ácido Ascórbico/administração & dosagem , Vitamina D/administração & dosagem , Zinco/administração & dosagem , Infecções por Coronavirus/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Avaliação em Saúde , Análise Custo-Benefício
12.
BMC Neurol ; 20(1): 255, 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32593295

RESUMO

BACKGROUND: Even though recent research has achieved significant advancement in the development of therapeutic approaches for Wilson's diseases (WD), the current treatment options available for WD are still limited, especially for WD patients with neurological symptoms. This study is intended to compare the therapeutic approaches for WD patients with neurological symptoms receiving either combined sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) and zinc treatment or D-penicillamine (DPA) monotherapy as first-line therapy, and identify the more effective therapeutic approach. METHODS: The case records of 158 patients diagnosed with neurological WD were retrospectively analyzed. These patients treated with intravenous DMPS + Zinc and in combination with oral zinc as a maintenance therapy (Group 1) or DPA alone (Group 2) for 1 year. During the period of treatment, the neurological symptoms of the patients were assessed using the Global Assessment Scale (GAS) and Barthel index. The key hematological and biochemical parameters of the patients (such as the levels of aminotransferase, serum ceruloplasmin, 24-h urine copper excretion), as well as adverse effects were recorded and analyzed. RESULTS: Ninety-three patients in Group 1, displayed decreased GAS scores and increased Barthel indexes consistently in comparison with the baseline (P < 0.01). Among them, 82 patients (88.2%) exhibited significant neurological improvement after 1 year, while 8 patients (8.6%) experienced neurological deterioration. Among the 65 patients in Group 2, 37 patients (58.5%) exhibited neurological improvements, while 17 patients (26.2%) experienced neurological deterioration after 1-year follow up. Six patients discontinued their treatment midway due to their exacerbating neurological symptoms. A comprehensive comparison of the effectiveness of the two courses of treatment revealed that patients in group 1 demonstrated a higher improvement ratio (P < 0.01) and lower worsening ratio of the neurological symptoms for the patients (P < 0.01) in comparison to the patients in group 2. Meanwhile, renal function, liver enzyme and blood cell counts remained stabilized in group1. CONCLUSIONS: This study indicates that the combined therapeutic approach of DPMS and zinc may be a preferred first-line therapy in treating the neurological symptoms of WD, in comparison to the treatment with DPA.


Assuntos
Quelantes/administração & dosagem , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/uso terapêutico , Unitiol/administração & dosagem , Zinco/administração & dosagem , Adulto , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
13.
Life Sci ; 256: 117993, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574664

RESUMO

Flavonoids are known for their wide range of bioactive properties including beneficial effect on bone formation. Their intense metal ion chelating capacity endorsed their nomination as a new biomaterial for biomedical applications. The present study examined the functional role of Kaemferal-Zinc(II) (Kaem-Zn) complex in bone formation, in vitro and in vivo. The cyto-compatibility assay confirmed that upto 25 µM of Kaem and Kaem-Zn complex was non-toxic. In fact, it facilitates ALP activity and accumulation of calcium in osteoblast; it was confirmed by Alizarin red and von Kossa staining. In addition to this, osteoblast markers, Runx2, type 1 col., ALP mRNAs expression, and osteocalcin and osteonectin secretory proteins level were also induced by the Kaem-Zn complex. Furthermore, bone forming ability of Kaem and Kaem-Zn was assessed by zebrafish model. The optimal concentration of Kaem and Kaem-Zn was determined by the viability assay of Zebrafish larvae. Osteoblasts distribution in scale, vertebrae and caudal fin ossification was studied by alizarin red staining accompanied by confocal imaging were carried out in adult zebrafish exposed to Kaem and Kaem-Zn complex. To sum up, our findings showed that Kaem promotes bone growth, and Kaem-Zn complex has further strengthened it. Kaem-Zn complex could be an effectively explored and used use in bone tissue engineering.


Assuntos
Quempferóis/administração & dosagem , Quempferóis/síntese química , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Zinco/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Peixe-Zebra , Zinco/química
14.
JAMA Netw Open ; 3(5): e204330, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32383748

RESUMO

Importance: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. Objective: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. Design, Setting, and Participants: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. Intervention: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo. Main Outcomes and Measures: The primary outcome was mortality risk measured as a change in Veterans Aging Cohort Study (VACS) Index score between baseline and 18 months. The VACS Index scores range from 0 to 164, with higher scores indicating higher mortality risk. Secondary outcomes were change in CD4 cell count between baseline and 18 months, the assessment of cardiovascular disease risk (Reynolds Risk Score, which ranges from 0% to 100%, with higher scores indicating higher risk), and changes in inflammatory or microbial translocation biomarkers at 18 months. Adjusted linear regression analyses were performed. Results: A total of 254 participants (184 men [72%]; mean [SD] age, 34 [6] years) were enrolled in the trial; 126 were randomized to receive zinc, and 128 were randomized to receive placebo. Participants had high CD4 cell counts (mean [SD], 521 [292] cells/mm3), and 188 (74%) reported heavy drinking in the past week. In the main analyses, zinc supplementation did not affect changes in the VACS Index score at 18 months (change for zinc, mean [SD], 0.49 [14.6]; median [interquartile range], 0.0 [-7.0 to 6.0]; change for placebo, mean [SD], 5.5 [17.2]; median [interquartile range], 6.0 [-6.0 to 14.0]; adjusted mean difference [AMD], -4.68; 95% CI, -9.62 to 0.25; P = .06) or any secondary outcomes, including change in CD4 cell count (AMD, 41.8 cells/mm3; 95% CI, -20.3 to 103.8 cells/mm3; P = .19), Reynolds Risk Score (AMD, -0.014; 95% CI, -0.167 to 0.139; P = .85), interleukin-6 level (AMD, -0.13 pg/mL; 95% CI, -0.38 to 0.11 pg/mL; P = .30), dimerized plasmin fragment D level (AMD, -0.21 µg/mL fibrinogen equivalent units; 95% CI, -0.48 to 0.07 µg/mL fibrinogen equivalent units; P = .14), soluble CD14 level (AMD, -38.01 ng/mL; 95% CI, -166.90 to 90.88 ng/mL; P = .56), intestinal fatty acid binding protein level (AMD, 0.08 pg/mL; 95% CI, -0.07 to 0.22 pg/mL; P = .32), and lipopolysaccharide binding protein level (AMD, -0.09 ng/mL; 95% CI, -0.23 to 0.06 ng/mL; P = .24). In the per-protocol analyses, zinc supplementation statistically significantly affected changes in the VACS Index score at 18 months (AMD, -7.49; 95% CI, -13.74 to -1.23; P = .02); however, the adherence rate to zinc supplementation was 51%. Conclusions and Relevance: Zinc supplementation did not reduce mortality risk, CD4 cell counts, cardiovascular disease risk, and levels of inflammation or microbial translocation in people with heavy alcohol use who are living with HIV/AIDS. Zinc supplementation did not change the VACS Index score but may have been limited by low adherence. Trial Registration: ClinicalTrials.gov Identifier: NCT01934803.


Assuntos
Transtornos Relacionados ao Uso de Álcool/complicações , Suplementos Nutricionais , Infecções por HIV/tratamento farmacológico , Veteranos , Zinco/administração & dosagem , Adolescente , Adulto , Idoso , Progressão da Doença , Método Duplo-Cego , Feminino , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Federação Russa , Resultado do Tratamento , Adulto Jovem
15.
Am J Gastroenterol ; 115(8): 1293-1297, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32467505

RESUMO

INTRODUCTION: This study aimed to assess the association between incident Crohn's disease (CD) or incident ulcerative colitis (UC) and dietary zinc intake. METHODS: NutriNet-Santé cohort's participants who completed at least three 24-hour dietary records were included and incident CD or UC cases were identified. Multivariable Poisson models were performed to assess associations between tertiles of zinc intake and CD or UC. RESULTS: Among the 105,832 participants, 27 reported incident CD and 48 reported incident UC. The relative risks of CD decreased with dietary zinc intakes. Compared with participants with the lowest tertile of zinc intake, the relative risks for CD were 0.60 (95% confidence interval [0.22-1.66]) and 0.12 (95% confidence interval [0.02-0.73]) for the second and the highest tertiles, respectively (Ptrend = 0.02). No significant association was observed for UC. DISCUSSION: Dietary zinc intake was inversely associated with incident CD.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Suplementos Nutricionais , Zinco/administração & dosagem , Adulto , Estudos de Coortes , Registros de Dieta , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Fatores de Risco
16.
Z Gerontol Geriatr ; 53(4): 295-302, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32468295

RESUMO

Selenium and zinc are essential trace elements and an inadequate dietary intake has been implicated in the decline of immune and cognitive functions in aged persons and in the pathogenesis of age-related disorders. Both micronutrients are often marketed as "antioxidants" in mineral supplements; however, neither selenium nor zinc are antioxidants per se but they may exert beneficial effects as components of enzymes and other proteins that catalyze redox reactions and/or are involved in the maintenance of redox homeostasis. According to epidemiological data older individuals have an increased risk of developing deficiencies in the selenium and zinc status; however, such statistical correlations in epidemiological studies do not imply a causal association. Intervention trials are scarce and have yielded inconsistent and sometimes even adverse results. It should also be noted that the observed deficiencies in micronutrients may not necessarily be attributable to inadequate dietary intake as the absorption and distribution within the body might also be influenced by factors such as medications or interaction with other food ingredients. Thus, any dietary supplementation should be implemented with caution and persons who wish to take mineral supplements should first seek medical advice. This article discusses the role of selenium and zinc in biological antioxidant systems, summarizes findings on the supply and supplementation of aged persons with these trace elements and on the influence they may exert on aging-related health issues, such as cognitive decline and type 2 diabetes mellitus.


Assuntos
Antioxidantes/administração & dosagem , Envelhecimento Saudável , Selênio/administração & dosagem , Zinco/administração & dosagem , Idoso , Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Humanos
17.
S D Med ; 73(4): 178-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32445306

RESUMO

In this report, we present a case of acquired copper deficiency which initially presented as progressive pain and numbness in the patient's lower extremities. The acquired copper deficiency is attributed to a previous bariatric surgery exacerbated by zinc toxicity. A 42-year-old female with a past medical history of type 2 diabetes mellitus, anemia, hypertension, bipolar disorder, attention deficit disorder, pulmonary embolus, fibromyalgia, migraine headaches, and chronic pain as well as a remote past surgical history of gastric bypass procedure presented with progressive pain and numbness in her lower extremities. The patient reported chronic use of zinc supplements. Clinical evaluation revealed abnormal neurologic exam consistent with a myeloneuropathy and anemia. A cervical spine MRI showed increased signal intensity primarily affecting the posterior columns from C2-C6. Laboratory studies confirmed low copper, low ceruloplasmin, and elevated zinc levels. This case is an example of acquired copper deficiency due to previous bariatric surgery exacerbated by zinc ingestion. With an increased prevalence of bariatric surgery, it is important to monitor patients postoperatively for neurologic symptoms potentially due to copper deficiency.


Assuntos
Cirurgia Bariátrica , Cobre , Diabetes Mellitus Tipo 2 , Doenças do Sistema Nervoso , Zinco , Adulto , Cobre/deficiência , Feminino , Humanos , Doenças do Sistema Nervoso/etiologia , Exame Neurológico , Zinco/administração & dosagem , Zinco/efeitos adversos
18.
Med Hypotheses ; 142: 109815, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32408070

RESUMO

Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.


Assuntos
Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Suplementos Nutricionais , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Zinco/administração & dosagem , Idoso , Betacoronavirus , Sinergismo Farmacológico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Tempo de Internação , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Modelos Teóricos , Pandemias , Segurança do Paciente , Zinco/farmacologia
19.
Am J Trop Med Hyg ; 103(1): 86-99, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342851

RESUMO

The common cold had resulted in significant economic and social burden worldwide. The effect of vitamin C on preventing common cold in healthy adults has been investigated extensively, but not that of other micronutrients. Thus, we aim to assess the effects of providing micronutrients singly through oral means, on cold incidence, and/or management (in terms of cold duration and symptom severity) in healthy adults from systematically searched randomized controlled trials. From four electronic databases, 660 identified studies were screened and data were extracted from 20 studies (zinc, 10; vitamin D, 8; and vitamins A and E, 2). The quality of selected studies was assessed using the Cochrane risk of bias tool and certainty in the outcomes was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. The review found that micronutrients supplementation, except vitamin C, may not prevent cold incidence or reduce symptom severity among healthy adults. However, zinc supplementation was observed to potentially reduce cold duration by 2.25 days (when zinc is provided singly, 95% CI: -3.39, -1.12). This suggests that zinc supplementation may reduce the overall burden due to common cold among healthy adults.


Assuntos
Ácido Ascórbico/administração & dosagem , Resfriado Comum/epidemiologia , Resfriado Comum/prevenção & controle , Suplementos Nutricionais , Zinco/administração & dosagem , Adolescente , Adulto , Idoso , Humanos , Incidência , Micronutrientes/administração & dosagem , Pessoa de Meia-Idade , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Vitamina A/administração & dosagem , Vitamina D/administração & dosagem , Vitamina E/administração & dosagem
20.
Biomater Sci ; 8(8): 2143-2155, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32248211

RESUMO

Among emerging biomaterials, bioactive glasses (BGs) are being widely explored for various applications in tissue engineering. However, the effects of BGs (in particular BG ionic dissolution products) on immune cells and specifically on dendritic cells (DCs), which are the most potent antigen-presenting cells of the immune system, have not been previously investigated in detail. Such interactions between BGs and DCs must be assessed as a novel biocompatibility criterion for biomaterials, since, with the increased application possibilities of BGs, the modulation of the immune system may induce potential complications and undesired side effects. Indeed, the effects of BG exposure on specific immune cells are not well understood. Thus, in this study we investigated, for the first time, the effect of borate BGs doped with biologically active ions on specific immune cells, such as DCs and we further investigated the antibacterial properties of these borate BGs. The compositions of the borate BGs (B3) were based on the well-known 13-93 (silicate) composition by replacing silica with boron trioxide and by adding copper (3 wt%) and/or zinc (1 wt%). By performing an agar diffusion test, the antibacterial effect depending on the compositions of the borate BGs could be proved. Furthermore we found a dose-dependent immune modulation of DCs after treatment with borate BGs, especially when the borate BGs contained Zn and/or Cu. Depending on the ion concentration and the rise in pH, the phenotype and function of DCs were modified. While at low doses B3 and Zn-doped B3 BGs had no impact on DC viability, Cu containing BGs strongly affected cell viability. Furthermore, the surface expression of DC-specific activation markers, such as the major histocompatibility complex (MHC)-II, CD86 and CD80, was modulated. In addition, also DC mediated T-cell proliferation was remarkably reduced when treated with high doses of B3-Cu and B3-Cu-Zn BGs. Interestingly, the release of inflammatory cytokines increased after incubation with B3 and B3-Zn BGs compared to mock-treated DCs. Considering the essential role of DCs in the modulation and regulation of immune responses, these findings provide first evidence of phenotypic and functional consequences regarding the exposure of DCs to BGs in vitro.


Assuntos
Antibacterianos/administração & dosagem , Boratos/administração & dosagem , Cobre/administração & dosagem , Células Dendríticas/efeitos dos fármacos , Vidro , Zinco/administração & dosagem , Animais , Antibacterianos/química , Boratos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cobre/química , Citocinas/metabolismo , Células Dendríticas/metabolismo , Vidro/química , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Zinco/química
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