RESUMO
Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, "long COVID". Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or "brain fog"), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance. Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent. Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit. Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases. This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration ("brain fog") and pain in the ME/CFS syndrome-like documented in long COVID. Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted.
Assuntos
Tratamento Farmacológico da COVID-19 , Síndrome de Fadiga Crônica , Melatonina , Humanos , Melatonina/uso terapêutico , SARS-CoV-2 , Síndrome de Fadiga Crônica/tratamento farmacológico , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de COVID-19 Pós-AgudaRESUMO
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by severe and persistent fatigue. Along with clinical studies showing endothelial dysfunction (ED) in a subset of ME/CFS patients, we have recently reported altered ED-related microRNAs in plasma from affected individuals. Inadequate nitric oxide (NO), mainly produced by the endothelial isoform of nitric oxide synthase (eNOS) in endothelial cells (ECs), is a major cause of ED. In this study, we hypothesized that plasma from that cohort of ME/CFS patients induces eNOS-related ED in vitro. To test this, we cultured human umbilical vein endothelial cells (HUVECs) in the presence of plasma from either ME/CFS patients (ME/CFS-plasma, n = 11) or healthy controls (HC-plasma, n = 12). Then, we measured the NO production in the absence and presence of tyrosine kinase and G protein-coupled receptors agonists (TKRs and GPCRs, respectively), well-known to activate eNOS in ECs. Our data showed that HUVECs incubated with ME/CFS-plasma produced less NO either in the absence or presence of eNOS activators compared to ones in presence of HC-plasma. Also, the NO production elicited by bradykinin, histamine, and acetylcholine (GPCRs agonists) was more affected than the one triggered by insulin (TKR agonist). Finally, inhibitory eNOS phosphorylation at Thr495 was higher in HUVECs treated with ME/CFS-plasma compared to the same treatment with HC-plasma. In conclusion, this study in vitro shows a decreased NO production in HUVECs exposed to plasma from ME/CFS patients, suggesting an unreported role of eNOS in the pathophysiology of this disease.
Assuntos
Síndrome de Fadiga Crônica , MicroRNAs , Estudos de Coortes , Células Endoteliais , Síndrome de Fadiga Crônica/tratamento farmacológico , Humanos , Óxido NítricoRESUMO
RESUMEN Se supone que aproximadamente 80 millones de personas a nivel mundial están infectadas con el virus de la hepatitis C. Un aproximado del 60 % de dichos pacientes aqueja síndrome de fatiga crónica. Se presentó un paciente portador de hepatitis crónica de tipo C, con manifestaciones clínicas de síndrome de fatiga crónica por más de dos años. Se han reportado estudios internacionales que han demostrado la relación existente entre el desarrollo de la respuesta inmune y el daño que ocasiona en el tejido cerebral la infección por virus de hepatitis C. Este trabajo tiene como objetivo la presentación del primer caso que se tiene referencia (AU).
ABSTRACT It is believed that almost 80 million persons are infected with the Hepatitis C virus around the world, and 60 % of them suffer the chronic fatigue syndrome. For that reason we present the case of a patient who is a carrier of the chronic fatigue syndrome for more than two years. Reports of international research have showed the relation between the immune answer and the damage caused by the infection of the hepatitis C virus in the brain tissues. The aim of this work is presenting the first case reported in Cuba (AU).
Assuntos
Humanos , Masculino , Síndrome de Fadiga Crônica/etiologia , Hepatite C/complicações , Antivirais/uso terapêutico , Qualidade de Vida , Síndrome de Fadiga Crônica/tratamento farmacológico , Interferons/efeitos adversos , Interferons/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Formação de AnticorposRESUMO
BACKGROUND: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19(+) B cells, CD56(bright) and CD56(dim) cell populations from CFS/ME patients. RESULTS: TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56(bright) TRPM3 35.72 % ± 7.37; CD56(dim) 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19(+) B cells (1.56 ± 0.191) and CD56(bright) NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19(+) B lymphocytes. CD56(bright) NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients. CONCLUSIONS: The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.
Assuntos
Linfócitos B/metabolismo , Síndrome de Fadiga Crônica/sangue , Células Matadoras Naturais/metabolismo , Canais de Cátion TRPM/metabolismo , Análise de Variância , Canais de Cálcio/sangue , Estudos de Casos e Controles , Inibidores Enzimáticos/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tapsigargina/uso terapêuticoRESUMO
BACKGROUND: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19+ B cells, CD56bnght and CD56dim cell populations from CFS/ME patients. RESULTS: TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56bright TRPM3 35.72 % ± 7.37; CD56dim 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19+ B cells (1.56 ± 0.191) and CD56bright NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19+ B lymphocytes. CD56bright NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients. CONCLUSIONS: The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfócitos B/metabolismo , Células Matadoras Naturais/metabolismo , Síndrome de Fadiga Crônica/sangue , Canais de Cátion TRPM/metabolismo , Valores de Referência , Canais de Cálcio/sangue , Estudos de Casos e Controles , Síndrome de Fadiga Crônica/tratamento farmacológico , Análise de Variância , Imunofenotipagem/métodos , Tapsigargina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Citometria de Fluxo/métodosRESUMO
We describe the effect of propranolol in an adolescent with chronic fatigue syndrome and orthostatic intolerance. Our observations suggest that the head-up tilt-test and beta-blocker treatment might be considered in patients with chronic fatigue syndrome and that enhanced sympathetic nervous activity might be part of the underlying pathophysiology.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , Hipotensão Ortostática/tratamento farmacológico , Propranolol/uso terapêutico , Adolescente , Síndrome de Fadiga Crônica/fisiopatologia , Humanos , Hipotensão Ortostática/fisiopatologia , MasculinoRESUMO
The use of sustained release tri-iodothyronine (SR-T3) in clinical practice, has gained popularity in the complementary and alternative medical community in the treatment of chronic fatigue with a protocol (WT3) pioneered by Dr. Denis Wilson. The WT3 protocol involves the use of SR-T3 taken orally by the patient every 12 hours according to a cyclic dose schedule determined by patient response. The patient is then weaned once a body temperature of 98.6 degrees F has been maintained for 3 consecutive weeks. The symptoms associated with this protocol have been given the name Wilson's Temperature Syndrome (WTS). There have been clinical studies using T3 in patients who are euthyroid based on normal TSH values. However, this treatment has created a controversy in the conventional medical community, especially with the American Thyroid Association, because it is not based on a measured deficiency of thyroid hormone. However, just as estrogen and progesterone are prescribed to regulate menstrual cycles in patients who have normal serum hormone levels, the WT3 therapy can be used to regulate metabolism despite normal serum thyroid hormone levels. SR-T3 prescription is based exclusively on low body temperature and presentation of symptoms. Decreased T3 function exerts widespread effects throughout the body. It can decrease serotonin and growth hormone levels and increase the number of adrenal hormone receptor sites. These effects may explain some of the symptoms observed in WTS. The dysregulation of neuroendocrine function may begin to explain such symptoms as alpha intrusion into slow wave sleep, decrease in blood flow to the brain, alterations in carbohydrate metabolism, fatigue, myalgia and arthralgia, depression and cognitive dysfunction. Despite all thermoregulatory control mechanisms of the body and the complex metabolic processes involved, WT3 therapy seems a valuable tool to re-establish normal body functions. We report the results of 11 patients who underwent the WT3 protocol for the treatment of CFS. All the patients improved in the five symptoms measured. All patients increased their basal temperature. The recovery time varied from 3 weeks to 12 months.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Síndrome de Fadiga Crônica/tratamento farmacológico , Tri-Iodotironina/administração & dosagem , Esquema de Medicação , HumanosRESUMO
The use of sustained release tri-iodothyronine (SR-T3) in clinical practice, has gained popularity in the complementary and alternative medical community in the treatment of chronic fatigue with a protocol (WT3) pioneered by Dr. Denis Wilson. The WT3 protocol involves the use of SR-T3 taken orally by the patient every 12 hours according to a cyclic dose schedule determined by patient response. The patient is then weaned once a body temperature of 98.6 degrees F has been maintained for 3 consecutive weeks. The symptoms associated with this protocol have been given the name Wilson's Temperature Syndrome (WTS). There have been clinical studies using T3 in patients who are euthyroid based on normal TSH values. However, this treatment has created a controversy in the conventional medical community, especially with the American Thyroid Association, because it is not based on a measured deficiency of thyroid hormone. However, just as estrogen and progesterone are prescribed to regulate menstrual cycles in patients who have normal serum hormone levels, the WT3 therapy can be used to regulate metabolism despite normal serum thyroid hormone levels. SR-T3 prescription is based exclusively on low body temperature and presentation of symptoms. Decreased T3 function exerts widespread effects throughout the body. It can decrease serotonin and growth hormone levels and increase the number of adrenal hormone receptor sites. These effects may explain some of the symptoms observed in WTS. The dysregulation of neuroendocrine function may begin to explain such symptoms as alpha intrusion into slow wave sleep, decrease in blood flow to the brain, alterations in carbohydrate metabolism, fatigue, myalgia and arthralgia, depression and cognitive dysfunction. Despite all thermoregulatory control mechanisms of the body and the complex metabolic processes involved, WT3 therapy seems a valuable tool to re-establish normal body functions. We report the results of 11 patients who underwent the WT3 protocol for the treatment of CFS. All the patients improved in the five symptoms measured. All patients increased their basal temperature. The recovery time varied from 3 weeks to 12 months.
Assuntos
Humanos , Preparações de Ação Retardada/administração & dosagem , Síndrome de Fadiga Crônica/tratamento farmacológico , Tri-Iodotironina , Temperatura Corporal/efeitos dos fármacos , Esquema de MedicaçãoRESUMO
OBJECTIVE: To compare effectiveness of oral therapy with reduced nicotinamide adenine dinucleotide (NADH) to conventional modalities of treatment in patients with chronic fatigue syndrome (CFS). BACKGROUND: CFS is a potentially disabling condition of unknown etiology. Although its clinical presentation is associated to a myriad of symptoms, fatigue is a universal and essential finding for its diagnosis. No therapeutic regimen has proven effective for this condition. METHODS: A total of 31 patients fulfilling the Centers for Disease Control criteria for CFS, were randomly assigned to either NADH or nutritional supplements and psychological therapy for 24 months. A thorough medical history, physical examination and completion of a questionnaire on the severity of fatigue and other symptoms were performed each trimester of therapy. In addition, all of them underwent evaluation in terms of immunological parameters and viral antibody titers. Statistical analysis was applied to the demographic data, as well as to symptoms scores at baseline and at each trimester of therapy. RESULTS: The twelve patients who received NADH had a dramatic and statistically significant reduction of the mean symptom score in the first trimester (p < 0.001). However, symptom scores in the subsequent trimesters of therapy were similar in both treatment groups. Elevated IgG and Ig E antibody levels were found in a significant number of patients. CONCLUSIONS: Observed effectiveness of NADH over conventional treatment in the first trimester of the trial and the trend of improvement of that modality in the subsequent trimesters should be further assessed in a larger patient sample.
Assuntos
Síndrome de Fadiga Crônica/tratamento farmacológico , NAD/uso terapêutico , Administração Oral , Adulto , Suplementos Nutricionais , Síndrome de Fadiga Crônica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia/métodos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: To compare effectiveness of oral therapy with reduced nicotinamide adenine dinucleotide (NADH) to conventional modalities of treatment in patients with chronic fatigue syndrome (CFS). BACKGROUND: CFS is a potentially disabling condition of unknown etiology. Although its clinical presentation is associated to a myriad of symptoms, fatigue is a universal and essential finding for its diagnosis. No therapeutic regimen has proven effective for this condition. METHODS: A total of 31 patients fulfilling the Centers for Disease Control criteria for CFS, were randomly assigned to either NADH or nutritional supplements and psychological therapy for 24 months. A thorough medical history, physical examination and completion of a questionnaire on the severity of fatigue and other symptoms were performed each trimester of therapy. In addition, all of them underwent evaluation in terms of immunological parameters and viral antibody titers. Statistical analysis was applied to the demographic data, as well as to symptoms scores at baseline and at each trimester of therapy. RESULTS: The twelve patients who received NADH had a dramatic and statistically significant reduction of the mean symptom score in the first trimester (p < 0.001). However, symptom scores in the subsequent trimesters of therapy were similar in both treatment groups. Elevated IgG and Ig E antibody levels were found in a significant number of patients. CONCLUSIONS: Observed effectiveness of NADH over conventional treatment in the first trimester of the trial and the trend of improvement of that modality in the subsequent trimesters should be further assessed in a larger patient sample
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , NAD , Síndrome de Fadiga Crônica/tratamento farmacológico , Administração Oral , Suplementos Nutricionais , Psicoterapia/métodos , Inquéritos e Questionários , Síndrome de Fadiga Crônica/psicologia , Resultado do TratamentoRESUMO
Endocrinologists were not included in the multidisciplinary working groups that prepared two recent reports on chronic fatigue syndrome, despite its unequalled clinical overlap with Addison's disease, which is a classic endocrine disorder. The failure to include at least one endocrinologist in those panels may explain why in their extensive reports there is not a single word about the 42 clinical features that chronic fatigue syndrome shares with Addison's disease, including all the signs and symptoms listed in the case definition of this syndrome.
Assuntos
Doença de Addison/classificação , Síndrome de Fadiga Crônica/classificação , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/tratamento farmacológico , Glucocorticoides/uso terapêutico , HumanosAssuntos
Doença de Addison/metabolismo , Encéfalo/metabolismo , Síndrome de Fadiga Crônica/metabolismo , Hipotensão Ortostática/etiologia , Oxigênio/metabolismo , Doença de Addison/complicações , Doença de Addison/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Química Encefálica , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/tratamento farmacológico , Fludrocortisona/uso terapêutico , Humanos , Hidrocortisona/uso terapêuticoRESUMO
The aim of the study was to determine the possible effect of melatonin treatment on disturbed sleep, fatigue and pain symptoms observed in fibromyalgia (FM) patients. Twenty-one consecutive patients with FM were included in an open 4-week-duration pilot study. Before and after treatment with melatonin 3 mg at bedtime, patients were evaluated using tender point count by palpation of 18 classic anatomical regions, pain score in four predesignated areas, pain severity on a 10 cm visual analogue scale (VAS), sleep disturbances, fatigue, depression, anxiety, and patient and physician global assessments, also by a VAS. Urine 6-sulphatoxymelatonin levels (aMT-6S) were measured in the patients and 20 age- and sex-matched controls. Nineteen patients completed the study. One patient withdrew because of migraine and another was lost to follow-up. At day 30, median values for the tender point count and severity of pain at selected points, patient and physician global assessments and VAS for sleep significantly improved with melatonin treatment. Other variables improved but did not reach statistical significance. Adverse events were mild and transient. Lower levels of aMT-6S were found in FM patients compared with normal median controls (+/-SD, 9.16 +/- 7.9 microg/24 h vs 16.8 +/- 12.8 microg/24 h) (p = 0.06). Although this is an open study, our preliminary results suggest that melatonin can be an alternative and safe treatment for patients with FM. Double-blind placebo controlled studies are needed.
Assuntos
Anticonvulsivantes/uso terapêutico , Fibromialgia/tratamento farmacológico , Melatonina/uso terapêutico , Administração Oral , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Síndrome de Fadiga Crônica/tratamento farmacológico , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/metabolismo , Feminino , Fibromialgia/complicações , Fibromialgia/metabolismo , Humanos , Melatonina/administração & dosagem , Melatonina/análogos & derivados , Melatonina/farmacocinética , Melatonina/urina , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Dor/metabolismo , Medição da Dor , Projetos Piloto , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/metabolismo , Resultado do TratamentoRESUMO
Os psicoestimulantes vêm sendo empregados como potencializadores de drogas antidepressivas no tratamento de transtornos do humor refratários. Mesmo nao associados a antidepressivos, os estimulantes sao considerados úteis no paciente deprimido portador de doença física e no idoso deprimido apático, nos quais os antidepressivos encontram obstáculos, especialmente efeitos colaterais e longa latência para o início da açao terapêutica. Sao particularmente interessantes para o paciente deprimido portador de doença física crônica terminal, como a AIDS e o câncer, e para o deprimido portador de lesao encefálica residual. No transtorno de déficit de atenção e hiperatividade residual do adulto, os psicoestimulantes sao indicados. Pacientes com transtornos do humor relacionados ao complexo demencial da AIDS também parecem beneficiar-se de terapêutica com psicoestimulante. Em casos da síndrome de fadiga crônica, psicoestimulantes também têm sido considerados úteis
Assuntos
Humanos , Anfetaminas/farmacocinética , Anfetaminas/uso terapêutico , Complexo AIDS Demência/tratamento farmacológico , Depressão/tratamento farmacológico , Dextroanfetamina/farmacocinética , Dextroanfetamina/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Metilfenidato/farmacocinética , Metilfenidato/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológicoRESUMO
El síndrome de fatiga crónica es una entidad clínica controvertida, cuyos síntomas y signos producen severas limitaciones en el estilo de vida y productividad de muchos pacientes. Fue definida en abril de 1987, por un grupo de trabajo de la División de Enfermedades Virales del C.D.C. en USA, según criterios clínicos mayores y menores. En su patogenia se han involucrado mecanismos metabólicos, infecciosos, neuroendocrinos, inmunológicos y psiquiátricos. Las pruebas de laboratorio muestran alteraciones inespecíficas y hasta la fecha no existe un tratamiento específico para esta enfermedad