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1.
Vitam Horm ; 115: 67-88, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33706965

RESUMO

Preservation of a robust circadian rhythmicity (particulsarly of the sleep/wake cycle), a proper nutrition and adequate physical exercise are key elements for healthy aging. Aging comes along with circadian alteration, e.g. a disrupted sleep and inflammation, that leads to metabolic disorders. In turn, sleep cycle disturbances cause numerous pathophysiological changes that accelerates the aging process. In the central nervous system, sleep disruption impairs several functions, among them, the clearance of waste molecules. The decrease of plasma melatonin, a molecule of unusual phylogenetic conservation present in all known aerobic organisms, plays a particular role as far as the endocrine sequels of aging. Every day, the late afternoon/nocturnal increase of melatonin synchronizes both the central circadian pacemaker located in the hypothalamic suprachiasmatic nuclei as well as myriads of peripheral cellular circadian clocks. This is called the "chronobiotic effect" of melatonin, the methoxyindole being the prototype of the endogenous family of chronobiotic agents. In addition, melatonin exerts a significant cytoprotective action by buffering free radicals and reversing inflammation via down regulation of proinflammatory cytokines, suppression of low degree inflammation and prevention of insulin resistance. Because of these properties melatonin has been advocated to be a potential therapeutic tool in COVID 19 pandemic. Melatonin administration to aged animals counteracts a significant number of senescence-related changes. In humans, melatonin is effective both as a chronobiotic and a cytoprotective agent to maintain a healthy aging. Circulating melatonin levels are consistently reduced in the metabolic syndrome, ischemic and non-ischemic cardiovascular diseases and neurodegenerative disorders like the Alzheimer's and Parkinson's diseases. The potential therapeutic value of melatonin has been suggested by a limited number of clinical trials generally employing melatonin in the 2-10mg/day range. However, from animal studies the cytoprotective effects of melatonin need higher doses to become apparent (i.e. in the 100mg/day range). Hence, controlled studies employing melatonin doses in this range are urgently needed.


Assuntos
Antioxidantes/farmacologia , Ritmo Circadiano/efeitos dos fármacos , Envelhecimento Saudável/efeitos dos fármacos , Melatonina/farmacologia , Animais , Antioxidantes/uso terapêutico , Humanos , Melatonina/uso terapêutico
2.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669456

RESUMO

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.


Assuntos
/tratamento farmacológico , Suplementos Nutricionais , Melatonina/uso terapêutico , Vitaminas/uso terapêutico , Zinco/uso terapêutico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Suplementos Nutricionais/análise , Alimento Funcional/análise , Humanos , Melatonina/farmacologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Vitaminas/farmacologia , Zinco/farmacologia
3.
Trials ; 22(1): 194, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685474

RESUMO

OBJECTIVES: We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N7 ". The registration date was February 16, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antioxidantes/uso terapêutico , Melatonina/uso terapêutico , Gasometria , Proteína C-Reativa/metabolismo , /fisiopatologia , Ferritinas/metabolismo , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico) , L-Lactato Desidrogenase/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Cochrane Database Syst Rev ; 2: CD013281, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591592

RESUMO

BACKGROUND: The prevalence of type 2 diabetes is increased in individuals with mental disorders. Much of the burden of disease falls on the populations of low- and middle-income countries (LMICs). OBJECTIVES: To assess the effects of pharmacological, behaviour change, and organisational interventions versus active and non-active comparators in the prevention or delay of type 2 diabetes among people with mental illness in LMICs. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase and six other databases, as well as three international trials registries. We also searched conference proceedings and checked the reference lists of relevant systematic reviews. Searches are current up to 20 February 2020. SELECTION CRITERIA: Randomized controlled trials (RCTs) of pharmacological, behavioural or organisational interventions targeting the prevention or delay of type 2 diabetes in adults with mental disorders in LMICs. DATA COLLECTION AND ANALYSIS: Pairs of review authors working independently performed data extraction and risk of bias assessments. We conducted meta-analyses using random-effects models. MAIN RESULTS: One hospital-based RCT with 150 participants (99 participants with schizophrenia) addressed our review's primary outcome of prevention or delay of type 2 diabetes onset. Low-certainty evidence from this study did not show a difference between atypical and typical antipsychotics in the development of diabetes at six weeks (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.03 to 7.05) (among a total 99 participants with schizophrenia, 68 were in atypical and 31 were in typical antipsychotic groups; 55 participants without mental illness were not considered in the analysis). An additional 29 RCTs with 2481 participants assessed one or more of the review's secondary outcomes. All studies were conducted in hospital settings and reported on pharmacological interventions. One study, which we could not include in our meta-analysis, included an intervention with pharmacological and behaviour change components. We identified no studies of organisational interventions. Low- to moderate-certainty evidence suggests there may be no difference between the use of atypical and typical antipsychotics for the outcomes of drop-outs from care (RR 1.31, 95% CI 0.63 to 2.69; two studies with 144 participants), and fasting blood glucose levels (mean difference (MD) 0.05 lower, 95% CI 0.10 to 0.00; two studies with 211 participants). Participants who receive typical antipsychotics may have a lower body mass index (BMI) at follow-up than participants who receive atypical antipsychotics (MD 0.57, 95% CI 0.33 to 0.81; two studies with 141 participants; moderate certainty of evidence), and may have lower total cholesterol levels eight weeks after starting treatment (MD 0.35, 95% CI 0.27 to 0.43; one study with 112 participants). There was moderate certainty evidence suggesting no difference between the use of metformin and placebo for the outcomes of drop-outs from care (RR 1.22, 95% CI 0.09 to 16.35; three studies with 158 participants). There was moderate-to-high certainty evidence of no difference between metformin and placebo for fasting blood glucose levels (endpoint data: MD -0.35, 95% CI -0.60 to -0.11; change from baseline data: MD 0.01, 95% CI -0.21 to 0.22; five studies with 264 participants). There was high certainty evidence that BMI was lower for participants receiving metformin compared with those receiving a placebo (MD -1.37, 95% CI -2.04 to -0.70; five studies with 264 participants; high certainty of evidence). There was no difference between metformin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels. Low-certainty evidence from one study (48 participants) suggests there may be no difference between the use of melatonin and placebo for the outcome of drop-outs from care (RR 1.00, 95% CI 0.38 to 2.66). Fasting blood glucose is probably reduced more in participants treated with melatonin compared with placebo (endpoint data: MD -0.17, 95% CI -0.35 to 0.01; change from baseline data: MD -0.24, 95% CI -0.39 to -0.09; three studies with 202 participants, moderate-certainty evidence). There was no difference between melatonin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels. Very low-certainty evidence from one study (25 participants) suggests that drop-outs may be higher in participants treated with a tricyclic antidepressant (TCA) compared with those receiving a selective serotonin reuptake inhibitor (SSRI) (RR 0.34, 95% CI 0.11 to 1.01). It is uncertain if there is no difference in fasting blood glucose levels between these groups (MD -0.39, 95% CI -0.88 to 0.10; three studies with 141 participants, moderate-certainty evidence). It is uncertain if there is no difference in BMI and depression between the TCA and SSRI antidepressant groups. AUTHORS' CONCLUSIONS: Only one study reported data on our primary outcome of interest, providing low-certainty evidence that there may be no difference in risk between atypical and typical antipsychotics for the outcome of developing type 2 diabetes. We are therefore not able to draw conclusions on the prevention of type 2 diabetes in people with mental disorders in LMICs. For studies reporting on secondary outcomes, there was evidence of risk of bias in the results. There is a need for further studies with participants from LMICs with mental disorders, particularly on behaviour change and on organisational interventions targeting prevention of type 2 diabetes in these populations.


Assuntos
Antipsicóticos/uso terapêutico , Países em Desenvolvimento , Diabetes Mellitus Tipo 2/prevenção & controle , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Antidepressivos Tricíclicos/uso terapêutico , Antioxidantes/uso terapêutico , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Jejum/sangue , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Melatonina/uso terapêutico , Transtornos Mentais/complicações , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/complicações , Inibidores de Captação de Serotonina/uso terapêutico
5.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540815

RESUMO

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin's effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.


Assuntos
Transtorno do Espectro Autista/complicações , Melatonina/farmacocinética , Transtornos Intrínsecos do Sono/tratamento farmacológico , Administração Oral , Adulto , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/psicologia , Disponibilidade Biológica , Criança , Pré-Escolar , Ritmo Circadiano , Preparações de Ação Retardada , Suplementos Nutricionais , Feminino , Humanos , Injeções Intravenosas , Masculino , Melatonina/administração & dosagem , Melatonina/análogos & derivados , Melatonina/fisiologia , Melatonina/uso terapêutico , Melatonina/urina , Receptores de Melatonina/fisiologia , Saliva/química , Estações do Ano , Serotonina/metabolismo , Transtornos Intrínsecos do Sono/etiologia , Transtornos Intrínsecos do Sono/fisiopatologia , Latência do Sono/efeitos dos fármacos , Transtornos do Comportamento Social/tratamento farmacológico , Transtornos do Comportamento Social/etiologia , Triptofano/metabolismo
6.
Actas dermo-sifiliogr. (Ed. impr.) ; 112: 0-0, 2021. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-196953

RESUMO

Researchers the world over are working to find the treatments needed to reduce the negative effects of coronavirus disease 2019 (COVID-19) and improve the current prognosis of patients. Several drugs that are often used in dermatology are among the potentially useful treatments: ivermectin, antiandrogenic agents, melatonin, and the antimalarial drugs chloroquine and hydroxychloroquine. These and other agents, some of which have proven controversial, are being scrutinized by the scientific community. We briefly review the aforementioned dermatologic drugs and describe the most recent findings relevant to their use against COVID-19


Frente a la necesidad de encontrar una alternativa terapéutica que logre disminuir el impacto negativo de la COVID-19 y mejore el pronóstico actual de los pacientes, investigadores de todo el mundo se esfuerzan por aportar información que nos acerque a esta meta. Dentro de los potenciales farmacos, existen algunos de uso frecuente en dermatología: los antipalúdicos (cloroquina e hidroxicloroquina), la ivermectina, los antiandrógenos y la melatonina. Tanto estos como otros tratamientos se encuentran en la mira de la comunidad científica, siendo algunos foco de polémica y controversia. En el presente trabajo relizamos una revisión breve de los fármacos previamente mencionados, presentando los más recientes hallazgos en relación a su uso en la COVID-19


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pandemias , Antimaláricos/uso terapêutico , Antiparasitários/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Cloroquina/uso terapêutico , Ivermectina/uso terapêutico , Melatonina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Antimaláricos/história , Antimaláricos/farmacologia , Antiparasitários/história , Antiparasitários/farmacologia , Antagonistas de Androgênios/história , Antagonistas de Androgênios/farmacologia , Cloroquina/história , Cloroquina/farmacologia , Ivermectina/história , Ivermectina/farmacologia , Melatonina/história , Melatonina/farmacologia , Hidroxicloroquina/história , Hidroxicloroquina/farmacologia
7.
Cochrane Database Syst Rev ; 12: CD009861, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33319916

RESUMO

BACKGROUND: Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods. OBJECTIVES: To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines. SEARCH METHODS: We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform. SELECTION CRITERIA: We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia. DATA COLLECTION AND ANALYSIS: One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures. MAIN RESULTS: We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines. AUTHORS' CONCLUSIONS: When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Melatonina/uso terapêutico , Procedimentos Cirúrgicos Operatórios/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alprazolam/uso terapêutico , Ansiolíticos/efeitos adversos , Viés , Clonidina/uso terapêutico , Esquema de Medicação , Humanos , Melatonina/efeitos adversos , Midazolam/uso terapêutico , Pessoa de Meia-Idade , Oxazepam/uso terapêutico , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/psicologia , Cuidados Pré-Operatórios , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
BMC Complement Med Ther ; 20(1): 353, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225948

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2, and responsible for a global pandemic. Despite there being no known vaccines or medicines that prevent or cure COVID-19, many traditional, integrative, complementary and alternative medicines (TICAMs) have been touted as the solution, as well as researched as a potential remedy globally. This study presents a bibliometric analysis of global research trends at the intersection of TICAM and COVID-19. METHODS: SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020, with results being exported on the same day. All publication types were included, however, articles were only deemed eligible if they made mention of one or more TICAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned. RESULTS: A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included China, the United States, India and Italy. The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were TICAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 TICAMs were mentioned across eligible articles, with the most common ones including: traditional Chinese medicine (n = 94), vitamin D (n = 67), melatonin (n = 16), phytochemicals (n = 12), and general herbal medicine (n = 11). CONCLUSIONS: This study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and TICAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of TICAM therapies and COVID-19.


Assuntos
Pesquisa Biomédica , Infecções por Coronavirus/tratamento farmacológico , Medicina Integrativa , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Bibliometria , Pesquisa Biomédica/tendências , China/epidemiologia , Terapias Complementares , Coronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Bases de Dados Factuais , Medicamentos de Ervas Chinesas , Humanos , Índia/epidemiologia , Itália/epidemiologia , Melatonina/uso terapêutico , Fitoterapia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Editoração , Estados Unidos/epidemiologia , Vitamina D/uso terapêutico
9.
PLoS One ; 15(10): e0240149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33006999

RESUMO

From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, non-severe symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Piridonas/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Bases de Dados de Produtos Farmacêuticos , Furina/metabolismo , Humanos , Melatonina/farmacologia , Pandemias , Piridonas/farmacologia
10.
Trials ; 21(1): 882, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106171

RESUMO

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. INCLUSION CRITERIA: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. CONTROL GROUP: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1ß (IL-1ß), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N5 ". The registration date was 14 August 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 the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/efeitos dos fármacos , Depressores do Sistema Nervoso Central/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Betacoronavirus/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Depressores do Sistema Nervoso Central/administração & dosagem , Depressores do Sistema Nervoso Central/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Método Duplo-Cego , Hospitalização , Humanos , Irã (Geográfico)/epidemiologia , Melatonina/administração & dosagem , Melatonina/efeitos adversos , Oxigênio/sangue , Pandemias , Placebos/administração & dosagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Segurança , Fatores de Tempo , Resultado do Tratamento
11.
Indian J Dent Res ; 31(4): 593-600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33107463

RESUMO

Background and Aims: Melatonin is an indolamine that is primarily secreted by the pineal gland. It has immunomodulatory as well as antioxidant properties. It is a potent anti-oxidant that protects against inflammation and cellular damage caused by reactive oxygen species, also has potent angiogenic function that adds on to the benefits of melatonin. As a result of these actions, melatonin may be useful as an adjuvant in the treatment of various conditions in the oral cavity. The aim of this study is to systematically evaluate the role of melatonin in periodontal disease. Methods: An extensive review of the scientific literature was carried out using PubMed, Science Direct, Google Scholar and the Cochrane base. Research articles were collected upto December 2017. Results: Melatonin may have beneficial effects in certain inflammatory oral pathologies, mainly periodontal diseases where they inhibit bone resorption destroy reactive oxygen species, stimulates osteoblastic differentiation. Salivary melatonin could also act as a risk indicator for periodontal diseases. Conclusion: Many studies showed that the melatonin levels in GCF, Saliva, Serum of patients suffering from chronic periodontitis is lowered suggesting that may play a pivotal role in protecting the tissue from damage caused by oxidative stress. However, there exists no data on the concentration needed, method of application for potential benefits. Randomized clinical trials in this field are needed to fill the lacunae and better improve our understanding.


Assuntos
Melatonina , Doenças Periodontais , Antioxidantes/uso terapêutico , Humanos , Melatonina/uso terapêutico , Estresse Oxidativo , Doenças Periodontais/terapia , Saliva
13.
Molecules ; 25(19)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992875

RESUMO

Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host's tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Viroses/tratamento farmacológico , Viroses/imunologia , Infecções por Coronavirus/metabolismo , Sistemas de Liberação de Medicamentos , Humanos , Melatonina/metabolismo , Mitocôndrias/metabolismo , Pandemias , Pneumonia Viral/metabolismo , Viroses/metabolismo
14.
Int J Med Sci ; 17(14): 2133-2146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922174

RESUMO

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Descoberta de Drogas , Melatonina/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Cisteína Endopeptidases , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Melatonina/uso terapêutico , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico
15.
Mol Biol Rep ; 47(10): 8229-8233, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32920757

RESUMO

COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Antivirais/uso terapêutico , Basigina/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Antivirais/farmacologia , Basigina/antagonistas & inibidores , Infecções por Coronavirus/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Melatonina/farmacologia , Pandemias , Pneumonia Viral/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Biomolecules ; 10(9)2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825327

RESUMO

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Melatonina/administração & dosagem , Melatonina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Homeostase/efeitos dos fármacos , Humanos , Melatonina/farmacologia , Pandemias
17.
Turk J Med Sci ; 50(6): 1504-1512, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-32777902

RESUMO

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed.


Assuntos
Envelhecimento , Antioxidantes/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Melatonina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Idoso , Envelhecimento/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Betacoronavirus , Infecções por Coronavirus/virologia , Suplementos Nutricionais , Humanos , Melatonina/metabolismo , Melatonina/farmacologia , Pandemias , Pneumonia Viral/virologia
18.
Biomolecules ; 10(8)2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784556

RESUMO

Neurodegenerative diseases are the second most common cause of death and characterized by progressive impairments in movement or mental functioning in the central or peripheral nervous system. The prevention of neurodegenerative disorders has become an emerging public health challenge for our society. Melatonin, a pineal hormone, has various physiological functions in the brain, including regulating circadian rhythms, clearing free radicals, inhibiting biomolecular oxidation, and suppressing neuroinflammation. Cumulative evidence indicates that melatonin has a wide range of neuroprotective roles by regulating pathophysiological mechanisms and signaling pathways. Moreover, melatonin levels are decreased in patients with neurodegenerative diseases. In this review, we summarize current knowledge on the regulation, molecular mechanisms and biological functions of melatonin in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, vascular dementia and multiple sclerosis. We also discuss the clinical application of melatonin in neurodegenerative disorders. This information will lead to a better understanding of the regulation of melatonin in the brain and provide therapeutic options for the treatment of various neurodegenerative diseases.


Assuntos
Ritmo Circadiano , Melatonina/fisiologia , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo , Doença de Alzheimer/metabolismo , Esclerose Amiotrófica Lateral/metabolismo , Animais , Ritmo Circadiano/efeitos dos fármacos , Demência Vascular/metabolismo , Humanos , Doença de Huntington/metabolismo , Melatonina/uso terapêutico , Esclerose Múltipla/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo
19.
Virus Res ; 287: 198108, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32768490

RESUMO

Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/virologia , Melatonina/farmacologia , Pneumonia Viral/virologia , Antioxidantes , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Melatonina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vacinação , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Viroses/tratamento farmacológico , Viroses/metabolismo , Viroses/virologia
20.
Psychosomatics ; 61(6): 585-596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32828569

RESUMO

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. OBJECTIVE: In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Antipsicóticos/uso terapêutico , Encefalopatias/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Delírio/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Pneumonia Viral/fisiopatologia , Betacoronavirus , Encefalopatias/psicologia , Depressores do Sistema Nervoso Central/uso terapêutico , Infecções por Coronavirus/psicologia , Delírio/fisiopatologia , Delírio/psicologia , Moduladores GABAérgicos/uso terapêutico , Humanos , Lorazepam/uso terapêutico , Melatonina/uso terapêutico , Pandemias , Pneumonia Viral/psicologia , Guias de Prática Clínica como Assunto
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