Methylene blue may have a role in the treatment of COVID-19
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ABSTRACT:
SUBMITTER: Ghahestani S
PROVIDER: S-EPMC7409924 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Project description:The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the most recent coronaviruses, which has infected humans, and caused the disease COVID-19. The World Health Organization has declared COVID-19 as a pandemic in March 2020. The SARS-CoV-2 enters human hosts majorly via the respiratory tract, affecting the lungs first. In few critical cases, the infection progresses to failure of the respiratory system known as acute respiratory distress syndrome acute respiratory distress syndrome may be further associated with multi-organ failure and vasoplegic shock. Currently, the treatment of COVID-19 involves use of antiviral and anti-cytokine drugs. However, both the drugs have low efficacy because they cannot inhibit the production of free radicals and cytokines at the same time. Recently, some researchers have reported the use of methylene blue (MB) in COVID-19 management. MB has been used since a long time as a therapeutic agent, and has been approved by the US FDA for the treatment of other diseases. The additional advantage of MB is its low cost. MB is a safe drug when used in the dose of < 2 mg/kg. In this review, the applicability of MB in COVID-19 and its mechanistic aspects have been explored and compiled. The clinical studies have been explained in great detail. Thus, the potential of MB in the management of COVID-19 has been examined.
| S-EPMC8352658 | biostudies-literature
Project description:BackgroundConvalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19.MethodsWe did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123.FindingsBetween Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention.InterpretationMethylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded.FundingGrifols, Crowdfunding campaign YoMeCorono.
| S-EPMC8828369 | biostudies-literature
Project description:COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.
| S-EPMC7440159 | biostudies-literature
Project description:BACKGROUND:Although methylene blue (MB) had long been proposed to counteract the effects of cyanide (CN) intoxication, research on its mechanisms of action and efficacy has been abandoned for decades. Recent studies on the benefits of MB in post-anoxic injuries have prompted us to reexamine the relevance of this historical observation. METHODS:Our study was performed in adult male Sprague-Dawley rats and on HEK293T epithelial cells. First, the effects and toxicity of MB (0-80?mg/kg) on circulation and metabolism were established in four urethane-anesthetized rats. Then nine rats received a lethal infusion of a solution of KCN (0.75?mg/kg/min) and were treated by either saline or MB, at 20?mg/kg, a dose that we found to be innocuous in rat and to correspond to a dose of about 4?mg/kg in humans. MB was also administered 5?min after the end of a sub-lethal exposure to CN in a separate group of 10 rats. In addition, ATP/ADP ratio, ROS production, mitochondrial membrane potential (??m) and cellular O2 consumption rate (OCR) were determined in HEK293T cells exposed to toxic levels of CN (200?µM for 10?min) before and after applying a solution containing MB (1-100?µM for 10?min). RESULTS:Methylene blue was found to be innocuous up to 50?mg/kg. KCN infusion (0.75?mg/kg/min) killed all animals within 7-8?min. MB (20?mg/kg) administered at the same time restored blood pressure, cardiac contractility and limited O2 deficit, allowing all the animals to survive, without any significant methemoglobinemia. When administered 5?min after a non-lethal CN intoxication, MB sped up the recovery of lactate and O2 deficit. Finally, MB was able to decrease the production of ROS and restore the ATP/ADP ratio, ??m as well as OCR of epithelial cells intoxicated by CN. CONCLUSIONS:The present observations should make us consider the potential interest of MB in the treatment of CN intoxication. The mechanisms of the antidotal properties of MB cannot be accounted for by the creation of a cyanomethemoglobinemia, rather its protective effects appears to be related to the unique properties of this redox dye, which, depending on the dose, could directly oppose some of the consequences of the metabolic depression produced by CN at the cellular level.
| S-EPMC6086742 | biostudies-literature
Project description:A promising alternative to antibiotics for treatment of Staphylococcus aureus infections is photodynamic inactivation (PDI), which employs a photosensitizer (PS) that produces cytotoxic reactive oxygen species (ROS) when exposed to molecular oxygen and antimicrobial blue light in the spectrum of 400-470 nm. Although the precise mechanistic basis of PDI has not been defined, the formation of ROS and free radicals that oxidize a number of cellular targets, including membrane lipids, damage to proteins and nucleic acids result in inactivation of essential cellular functions and subsequent cell death. Because PDI is non-selective and affects multiple cellular targets, development of resistance or tolerance to PDI has been considered to be unlikely and attempts to induce S. aureus resistance or tolerance upon repeated sub-lethal doses of PDI have not succeeded. However, multiple aspects of PDI suggest that development of tolerance is highly probable, in particular when PDI is used for treatment of infections where the environment at the infection site prevents penetration of PDI at a level sufficient to cause death of all bacteria and with tolerant phenotypes emerging from the surviving bacteria. In this study, we sought to identify the mechanisms that contribute to PDI tolerance in S. aureus. S. aureus HG003 and the isogenic HG003DmutSL strain with defects in DNA mismatch repair were used to evaluate the response of S. aureus and the roles of DNA mismatch repair and gene regulatory networks to repeated sublethal doses of PDI. Global transcriptome and genome analyses were used in an agnostic approach to identify the underlying transcriptional responses and genetic adaptations that occur as a result of repeated PDI and contribute to PDI tolerance. Our results reveal multiple metabolic, transport and cell wall biogenesis pathways that contribute to PDI tolerance, and a S. aureus regulatory gene likely responsible for the adaptive transcriptional response to PDI.
2020-07-01 | GSE153561 | GEO
Project description:BACKGROUND:Methylene blue (MB) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. MB has been shown to be effective in inhibiting Plasmodium falciparum in culture, in the mouse model and in rhesus monkeys. MB was also shown to have a potent ex vivo activity against drug-resistant isolates of P. falciparum and P. vivax. In preclinical studies, MB acted synergistically with artemisinin derivates and demonstrated a strong effect on gametocyte reduction in P. falciparum. MB has, thus, been considered a potentially useful partner drug for artemisinin-based combination therapy (ACT), particularly when elimination is the final goal. The aim of this study was to review the scientific literature published until early 2017 to summarise existing knowledge on the efficacy and safety of MB in the treatment of malaria. METHODS:This systematic review followed PRISMA guidelines. Studies reporting on the efficacy and safety of MB were systematically searched for in relevant electronic databases according to a pre-designed search strategy. The search (without language restrictions) was limited to studies of humans published until February 2017. RESULTS:Out of 474 studies retrieved, a total of 22 articles reporting on 21 studies were eligible for analysis. The 21 included studies that reported data on 1504 malaria patients (2/3 were children). Older studies were case series and reports on MB monotherapy while recent studies were mainly controlled trials of combination regimens. MB was consistently shown to be highly effective in all endemic areas and demonstrated a strong effect on P. falciparum gametocyte reduction and synergy with ACT. MB treatment was associated with mild urogenital and gastrointestinal symptoms as well as blue coloration of urine. In G6PD-deficient African individuals, MB caused a slight but clinically non-significant haemoglobin reduction. CONCLUSIONS:More studies are needed to define the effects of MB in P. falciparum malaria in areas outside Africa and against P. vivax malaria. Adding MB to ACT could be a valuable approach for the prevention of resistance development and for transmission reduction in control and elimination programs. SYSTEMATIC REVIEW REGISTRATION:This study is registered at PROSPERO (registration number CRD42017062349 ).
| S-EPMC5979000 | biostudies-literature
Project description:In this work, an innovative nano-carbon material (N-CM) adsorbent was reported for exploring its adsorption behaviors toward cationic methylene blue (MB) and anionic reactive blue 19 (RB19) pollutants. The proposed N-CM was synthesized by a one-step solvothermal treatment of citric acid and zinc gluconate small precursors. N-CM consists of nanosheets that have an advantageous specific surface area, large sp2/sp3 hybridized domains, and abundant nitrogen/oxygen-containing surface functional groups. The synergistic effects of these features are conducive to the MB and RB19 adsorption. Different from anionic RB19 adsorption (79.54 mg/g) by the cooperative π-π stacking and hydrogen bonding, cationic MB adsorbed onto N-CM mainly by the electrostatic attraction at the natural pH solution (> pHpzc), with an adsorption capacity up to 118.98 mg/g. Interestingly, both MB and RB19 adsorption conformed to the pseudo-second order kinetic (R2 ≥ 0.995) and Langmuir isothermal (R2 ≥ 0.990) models, accompanied by similar maximum monolayer adsorption capacities of 120.77 and 116.01 mg/g, respectively. Their adsorption processes exhibited spontaneously endothermic characteristics. Moreover, N-CM showed superior selective capability toward MB in different mixed dye systems, with high removal efficiencies of 73-89%. These results demonstrate that the high-performance carbon adsorbent prepared from small precursors via low-temperature carbonization shows great potentials in wastewater treatment.
| S-EPMC9182342 | biostudies-literature
Project description:UNLABELLED: BACKGROUND:We aimed to minimalize operative complications by spraying of methylene blue stain on thyroid glands and the perithyroidal area. MATERIAL AND METHODS:The intra-operative methylene blue spraying technique was used prospectively on a total of 56 patients who had undergone primary (not recurrent) thyroid surgery for a variety of thyroid diseases. Bilateral total thyroidectomy was performed in all cases. After superior but before inferior pole ligation, 0.5ml of methylene blue was sprayed over the thyroid lobe and perilober area. Tissues, especially parathyroides, the recurrent laryngeal nerve, and the inferior thyroid artery, were identified and evaluated. RESULTS:Recurrent laryngeal nerve and arteries were not stained and thus they remained white in all cases while all other tissues were stained blue. Within three minutes parathyroid glands washed out the blue stain and the original yellow color was regained. Thyroid tissue wash-out time was not less than 15 minutes; perithyroideal muscles, tendinous and lipoid structures took no less than 25 minutes. CONCLUSION:The safety of intravascular methylene blue guidance on thyroid surgery is known. This research demonstrates the effectiveness of the spraying technique, a new technique which ensures not only identification of parathyroid glands within three minutes, but also identification of recurrent laryngeal nerves and inferior thyroid arteries.
| S-EPMC3539958 | biostudies-literature
Project description: Not available
| S-BSST563 | biostudies-other
Project description:IntroductionNeurofibrillary tangles (NFT) composed of Tau are hallmarks of neurodegeneration in Alzheimer disease. Transgenic mice expressing full-length pro-aggregant human Tau (2N4R Tau-ΔK280, termed Tau(ΔK)) or its repeat domain (TauRD-ΔK280, TauRD(ΔK)) develop a progressive Tau pathology with missorting, phosphorylation, aggregation of Tau, loss of synapses and functional deficits. Whereas TauRD(ΔK) assembles into NFT concomitant with neuronal death, Tau(ΔK) accumulates into Tau pretangles without overt neuronal loss. Both forms cause a comparable cognitive decline (with onset at 10mo and 12mo, respectively), which is rescued upon switch-off of transgene expression. Since methylene blue (MB) is able to inhibit Tau aggregation in vitro, we investigated whether MB can prevent or rescue Tau-induced cognitive impairments in our mouse models. Both types of mice received MB orally using different preventive and therapeutic treatment protocols, initiated either before or after disease onset. The cognitive status of the mice was assessed by behavior tasks (open field, Morris water maze) to determine the most successful conditions for therapeutic intervention.ResultsPreventive and therapeutic MB application failed to avert or recover learning and memory deficits of TauRD(ΔK) mice. Similarly, therapeutic MB treatment initiated after onset of cognitive impairments was ineffective in Tau(ΔK) mice. In contrast, preventive MB application starting before onset of functional deficits preserved cognition of Tau(ΔK) mice. Beside improved learning and memory, MB-treated Tau(ΔK) mice showed a strong decrease of insoluble Tau, a reduction of conformationally changed (MC1) and phosphorylated Tau species (AT180, PHF1) as well as an upregulation of protein degradation systems (autophagy and proteasome). This argues for additional pleiotropic effects of MB beyond its properties as Tau aggregation inhibitor.ConclusionsOur data support the use of Tau aggregation inhibitors as potential drugs for the treatment of AD and other tauopathies and highlights the need for preventive treatment before onset of cognitive impairments.
| S-EPMC4425867 | biostudies-literature