Methylene blue in covid-19.

SARS-CoV-2 infection generally begins in the respiratory tract where it can cause bilateral pneumonia. The disease can evolve into acute respiratory distress syndrome and multi-organ failure, due to viral spread in the blood and an excessive inflammatory reaction including cytokine storm. Antiviral and anti-cytokine drugs have proven to be poorly or in-effective in stopping disease progression, and mortality or serious chronic damage is common in severely ill cases. The low efficacy of antiviral drugs is probably due to late administration, when the virus has triggered the inflammatory reaction and is no longer the main protagonist. The relatively poor efficacy of anti-cytokine drugs is explained by the fact that they act on one or a few of the dozens of cytokines involved, and because other mediators of inflammation - reactive oxygen and nitrogen species - are not targeted. When produced in excess, reactive species cause extensive cell and tissue damage. The only drug known to inhibit the excessive production of reactive species and cytokines is methylene blue, a low-cost dye with antiseptic properties used effectively to treat malaria, urinary tract infections, septic shock, and methaemoglobinaemia. We propose testing methylene blue to contrast Covid-related acute respiratory distress syndrome, but particularly suggest testing it early in Covid infections to prevent the hyper-inflammatory reaction responsible for the serious complications of the disease.

Antipsychotic-induced metabolic and cardiovascular side effects in schizophrenia: a novel mechanistic hypothesis.

The use of antipsychotics is hindered by the frequent occurrence of metabolic and cardiovascular side effects, resulting in worsened quality of life and greater mortality as a result of cardiovascular and cerebrovascular disorders in schizophrenia patients than the comparable general population. The various antipsychotics induce extrapyramidal symptoms, impaired glucose and lipid metabolism, weight gain, hypertension and arrhythmias, with variable frequency. Second-generation antipsychotics appear to have several advantages over first-generation antipsychotics, including a claimed better action on cognitive function and the negative symptoms of schizophrenia, and lower frequency of extrapyramidal side effects; however, their use is associated with a greater frequency of metabolic and cardiovascular disturbances. The mechanisms of these important side effects are not well understood, and generic approaches (psychoeducational programmes and symptomatic therapies) have been proposed to limit their severity. Extensive data from the literature indicate that autonomic nervous system dysfunction--intrinsic to schizophrenia and strongly exacerbated by antipsychotic treatment--is the cause of the pervasive metabolic and vascular dysfunctions associated with schizophrenia. In this article, we marshal further literature data to argue that the metabolic and cardiovascular side effects of antipsychotics are primarily mediated by their ability to block peripheral dopamine receptors, which physiologically modulate sympathetic activity. We also propose that these effects might be overcome by providing peripheral dopaminergic stimulation.

La medicación dopaminérgica podría ser útil para mejorar el síndrome metabólico en la enfermedad de Parkinson / Dopaminergic medication could be of use in improving metabolic syndrome in Parkinson’s disease

Realizamos un estudio de casos y controles con 483 pacientes consecutivos con enfermedad de Parkinson idiopática (EP) y 533 controles apareados por edad y sexo con el fin de investigar la relación entre la EP y los factores de riesgo de enfermedades cardiovasculares. Mediante análisis multivariado, la diabetes, la hipertensión, los antecedentes de tabaquismo, colesterol elevado y altos niveles de triglicéridos fueron significativamente menos frecuentes en la EP que en los controles. Además, estas asociaciones resultaban más evidentes para los pacientes tratados con levodopa. Interpretamos esta asociación entre EP y reducción de los factores de riesgo vascular como debidos a insuficiencia en el eje hipotálamo-hipófisosuprarrenal, desnervación simpática generalizada en la EP y estimulación central o periférica de los receptores dopamínicos D1 y D2 por la levodopa. Estos efectos cardiovasculares y metabólicos favorables sugieren que la medicación dopaminérgica puede resultar útil en el tratamiento de los trastornos cardiovasculares.

La medicación dopaminérgica podría ser útil para mejorar el síndrome metabólico en la enfermedad de Parkinson / Dopaminergic medication could be of use in improving metabolic syndrome in Parkinsons disease

Realizamos un estudio de casos y controles con 483 pacientes consecutivos con enfermedad de Parkinson idiopática (EP) y 533 controles apareados por edad y sexo con el fin de investigar la relación entre la EP y los factores de riesgo de enfermedades cardiovasculares. Mediante análisis multivariado, la diabetes, la hipertensión, los antecedentes de tabaquismo, colesterol elevado y altos niveles de triglicéridos fueron significativamente menos frecuentes en la EP que en los controles. Además, estas asociaciones resultaban más evidentes para los pacientes tratados con levodopa. Interpretamos esta asociación entre EP y reducción de los factores de riesgo vascular como debidos a insuficiencia en el eje hipotálamo-hipófisosuprarrenal, desnervación simpática generalizada en la EP y estimulación central o periférica de los receptores dopamínicos D1 y D2 por la levodopa. Estos efectos cardiovasculares y metabólicos favorables sugieren que la medicación dopaminérgica puede resultar útil en el tratamiento de los trastornos cardiovasculares.(AU)

Sympathetic modulation by levodopa reduces vascular risk factors in Parkinson disease.

BACKGROUND: Sympathetic nervous system hyperactivity promotes vascular disorders by its catabolic effects and by increasing arterial blood pressure. Levodopa-derived dopamine modulates sympathetic overactivity and is known to reduce blood pressure, but its effects on glucose and lipid metabolism have not been studied in large series of patients. METHODS: We retrospectively examined 483 consecutive parkinsonian patients, admitted to a single institute between 1970 and 1987, before statins were available. We compared risk factors for vascular disease in the 305 who were on levodopa with the 178 who had never received the drug. RESULTS: On admission levodopa-treated patients had significantly lower plasma levels of triglycerides, total cholesterol and lipids, and lower frequency of diabetes and hypertension than untreated patients. Mean body mass index, resting blood pressure, fasting plasma glucose, and smoking did not differ between the groups. A year after enrollment 160 patients were re-hospitalized; of these 63 had started levodopa during first hospitalization. In these new levodopa users total cholesterol, triglycerides and lipids had reduced to levels comparable with those of longer-term levodopa users. CONCLUSION: Levodopa use in parkinsonian patients is associated with reduced vascular risk factors. In causal terms this finding might be attributed to the inhibitory action of levodopa-derived dopamine on the sympathetic nervous system.

Autonomic nervous system and risk factors for vascular disease. Effects of autonomic unbalance in schizophrenia and Parkinson's disease.

Alterations of the cardiovascular system and of the glucose and lipid metabolism can represent important factors of vascular risk. The autonomic nervous system, through its two efferent branches, the parasympatheticcholinergic and the sympathetic-adrenergic, plays an important role in the control of the cardiovascular activity and of the glucose and lipid metabolism, and its impaired working can interfere with these functions. An increased sympathetic activity and an increased frequency of diabetes, dyslipidemia, hypertension and obesity have been reported in untreated schizophrenic patients, and a further worsening of these vascular risk factors has been signalled as a side effect of treatment with neuroleptic drugs. The opposite is observed in Parkinson's disease, where the reduced autonomic activity induced by the illness is associated with a decreased frequency of vascular risk factors, and their occurrence is further reduced by the treatment with dopaminergic drugs.

Reduced risk factors for vascular disorders in Parkinson disease patients: a case-control study.

BACKGROUND AND PURPOSE: Sympathetic hyperactivity is a contributing cause of vascular disorders because it increases blood pressure, blood sugar, and blood lipids. Pervasive compromise of the central and peripheral autonomic nervous systems is common in idiopathic Parkinson disease (IPD) resulting in reduced sympathetic and parasympathetic function. We hypothesized that IPD was associated with reduced prevalence of cardiovascular disease risk factors as a result of reduced sympathetic activity. METHODS: We performed a retrospective case-control study on 178 newly diagnosed consecutive IPD patients, and 533 age- (+/-3 years) and sex-matched controls with other neurological diseases seen over the same period at the same hospital. For each case and control the following were noted on admission: smoking, diabetes, hypertension, body mass index, serum glucose, plasma cholesterol, triglycerides and total lipid levels, and blood pressure. RESULTS: Diabetes, history of smoking, high blood pressure, high blood glucose, high blood cholesterol, and triglycerides were significantly less frequent in IPD than controls. CONCLUSIONS: IDP is a natural model of impaired hypothalamic-pituitary-adrenal axis activity and generalized sympathetic denervation. We interpret the association of untreated IPD with reduced vascular diseases risk factors as attributable to reduced autonomic activity, suggesting that autonomic hyperactivity may be involved in the pathogenesis of vascular disorders.