Methylene Blue Administration Research Articles

Methylene blue therapy in addition to standard treatment for acute-phase septic shock: a pilot randomized controlled trial.

Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase. To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group. This was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6). MB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group. Early administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock. https://clinicaltrials.gov/, identifier RBR-96584w4.

Evaluation of the Efficacy of Methylene Blue Administration in SARS-CoV-2-Affected Patients: A Proof-of-Concept Phase 2, Randomized, Placebo-Controlled, Single-Blind Clinical Trial

The SARS-CoV-2 pandemic has revolutionized the scientific and medical world in recent years. Methylene blue (MB) is a well-known molecule. The aim of our study was to assess the efficacy of MB against early-phase SARS-CoV-2 infections. All patients with a positive swab for SARS-CoV-2 were eligible for the trial. The intervention was a starting dose of 200 mg MB or placebo in the morning and 100 mg in the evening on the first day and afterwards the standard daily dose of 200 mg. Patients were followed up for safety and efficacy until day 84. We analyzed 21 patients for the safety profile and 19 for the efficacy objective: of these, there were 11 in the MB group and 8 in the placebo one. In both groups, patients had undetectable RNA from day 3 and 10 out of 11 subjects in the MB group were virus free by day 12 vs. 6 out of 8 in the placebo one. None of the patients experienced serious adverse events. MB has proved to be a safe and well-tolerated drug. We did not find superiority of efficacy or viral clearance of MB compared to the placebo. Given the good in vitro efficacy, larger studies are needed to assess MB efficacy against COVID-19 in vivo.

Methylene blue for COVID-19 ARDS: insights from a randomized Clinical Trial.

Around the world, the COVID-19 pandemic has presented many difficulties, and acute respiratory distress syndrome (ARDS) has become a major worry. The antiviral and anti-inflammatory characteristics of methylene blue (MB) have garnered interest for potential medicinal applications. The object of the current study is to assess the effect of orally administered MB on the treatment of ARDS associated with COVID-19. A randomized clinical study was carried out on 122 hospitalized patients who had ARDS related to COVID-19. Patients who met the eligibility requirements were randomized at random to either the control group (CG) (n = 60) or the intervention group (IG) (n = 62). Standard treatments were administered to both groups, with the addition of oral MB to the IG. Clinical outcomes, including SpO2 levels, CRP levels were assessed on the third and fifth days. Additionally, at the time of discharge, patients' assessments were made in terms of APACHE II scores, SOFA scores, LDH and CRP levels, SpO2, and respiratory rate in comparison to the day prior to the intervention. Patients were followed for mortality outcomes at one month and three months after the intervention. Significant changes were observed in SpO2 levels over time (P < 0.001) and between groups (P = 0.022), with higher levels in the MB-treated group. The interaction between time and group (P = 0.019) indicated a stronger increase in SpO2 in the IG, with the IG's SpO2 level increasing by 6.42%. Furthermore, CRP levels showed significant changes over time (P < 0.001), but not between groups (P = 0.092). However, the interaction between group and CRP change over time (P = 0.019) suggested a distinct pattern of CRP decrease in the IG. Significant improvement in RR, SpO2, CRP, and APACHE II score were found according to discharge results. However, in terms of SpO2 and the APACHE II score, this improvement was noteworthy for IG. The length of hospitalization and mortality rates at one- and three-month follow-ups did not differ significantly. Oral administration of MB demonstrated positive effects on improving SpO2 levels and reducing inflammatory markers in COVID-19-related ARDS patients. Despite no significant impact on survival rates or hospitalization length, the study supports the potential efficacy of MB as an alternative treatment for COVID-19 ARDS. This study was registered with the Iranian Registry of Clinical Trials ( http://www.irct.ir ) under the registration code IRCT20200409047007N2 on 11/29/2021.

Photodynamic therapy with methylene blue and chlorin e6 photosensitizers: study on Ehrlich carcinoma mice model

Hypoxia negatively affcts the effctiveness of all types of anticancer therapy, in particular photodynamic therapy (PDT). In this regard, various approaches to overcome the limitations associated with hypoxia are widely discussed in the literature, one of them is the use of photosensitizers (PS) operating through the fist mechanism of the photodynamic reaction, such as methylene blue (MB). Previously, we have demonstrated that MB can have a positive effect on tumor oxygenation. In this work, we investigated the photodynamic activity of MB and a combination of MB with chlorin e6 on a tumor in vivo using a model of Ehrlich carcinoma. PDT was studied with the joint and separate administration of chlorin e6 and MB. The accumulation and localization of MB and its combination with chlorin e6 in vivo was assessed using video ˛uorescence and spectroscopic methods, and the effect of laser exposure on accumulation was analyzed. After the PDT with chlorin e6, MB and a combination of MB with chlorin e6, a good therapeutic effect and a decrease in the tumor growth rate were observed compared to the control, especially in groups with PDT with MB and with the simultaneous administration of chlorin e6 and MB. The level of tumor oxygenation on days 3 and 5 after PDT was higher for groups with irradiation, the highest oxygenation on the 5th day after PDT was observed in the group with PDT only with MB. Phasor diagrams of tumors after PDT show a deviation from the metabolic trajectory and a shift towards a longer lifetimes compared to the control tumor, which indicates the presence of lipid peroxidation products. Thus, tumor regression after PDT is associated with the direct destruction of tumor cells under the in˛uence of reactive oxygen species formed during PDT. Thus, the effectiveness of PDT with the combined use of MB and chlorin e6 has been demonstrated, and the main mechanisms of the antitumor effect of the combination of these PS have been studied.

Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis.

Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock. We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024. We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration. Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events. Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed. Center for Open Science (https://osf.io/hpy4j).

Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging.

Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species. To investigate the effect of long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice. Although we observed some beneficial effects of MB and MitoQ in vitro, the administration of these compounds in vivo did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 in UM-HET3 mice. Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.

The use of methylene blue to control the tumor oxygenation level

BackgroundHypoxia is a characteristic feature of many tumors. It promotes tumor proliferation, metastasis, and invasion and can reduce the effectiveness of many types of cancer treatment. ObjectiveThe aim of this study was to investigate the pharmacokinetics of methylene blue (MB) and its impact on the tumor oxygenation level at mouse Lewis lung carcinoma (LLC) model using spectroscopic methods. ApproachThe pharmacokinetics of MB were studied qualitatively and quantitatively using video fluorescence imaging and fluorescence spectroscopy. The degree of hemoglobin oxygenation in vivo was examined by calculating hemoglobin optical absorption from the measured diffuse reflectance spectra. The distribution of MB fluorescence and the lifetime of NADH were analyzed using laser scanning microscopy and fluorescence lifetime imaging microscopy (FLIM) to assess cellular metabolism. ResultsAfter intravenous administration of MB at 10–20 mg/kg, it quickly transitioned in the tumor to a colorless leucomethylene blue, with maximum accumulation in the tumor occurring after 5–10 min. A concentration of 10 mg/kg resulted in a relative increase of the tumor oxygenation level for small tumors (volume 50–75 mm3) and normal tissue 120 min after the introduction of MB. A shift in tumor metabolism towards oxidative phosphorylation (according to the lifetime of the NADH coenzyme) was measured using FLIM method after intravenous administration of 10 mg/kg of MB. Intravenous administration of MB at 20 mg/kg results in a long-term decrease in oxygenation, which persisted for at least 120 min after the administration and did not return to its initial level. ConclusionsAdministration of MB at 10 mg/kg shown to increase tumor oxygenation level, potentially leading to more effective antitumor therapy. However, at higher doses (20 mg/kg), MB may cause long-term decrease in oxygenation.

Methylene Blue in Metformin Intoxication: Not Just Rescue But Also Initial Treatment.

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.

Use of hydroxocobalamin to treat intraoperative vasoplegic syndrome refractory to vasopressors and methylene blue during liver transplantation.

For patients with catecholamine-resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series. We retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery. One hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12. Immediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response.

Metahemoglobinemia inducida por dapsona: reporte de un caso en el servicio de urgencia

Methemoglobinemia is a low prevalence but potentially severe condition in the Emergency Department. One of its leading causes is drug induction, dapsone being one of them. Dapsone is a synthetic sulfone with antimicrobial properties, often prescribed for prophylaxis against Pneumocystis jiroveci infection and other implications. This report presents the case of a 39-year-old male recently diagnosed with HIV on antiretroviral therapy along with prophylactic dapsone, who sought medical attention in the emergency room due to symptoms of cough, dyspnea, and fever. On admission, the patient exhibited a state of tachypnea and an oxygen saturation of 78% in room air, which is partially corrected with supplemental oxygen at an inspired oxygen fraction of 50%, achieving oxygen saturation of 90% by pulse oximetry. Chest X-ray revealed no abnormalities, and arterial blood gas analysis showed a partial pressure of oxygen of 380 mmHg with oxygen saturation of 100%. Given the disparity between pulse oximetry, arterial blood gas results, and the normal chest X-ray, a co-oximetry was conducted, revealing a methemoglobin level of 10.4% The patient was admitted to the ICU and continued receiving oxygen therapy. Dapsone was discontinued and the patient’s condition improved. without the need for methylene blue administration or alternative therapies.

Linfonodo ilíaco medial como alvo de metástase em cadelas com neoplasmas mamários malignos

ABSTRACT: The regional lymphatic connections of the mammary glands in canines are poorly investigated, both in healthy animals and in those with mammary neoplasms. The objective was to establish the occurrence of metastases in the medial iliac lymph nodes (MILN) in bitches with mammary neoplasm, in addition to evaluating the effectiveness of the technique of lymphatic labeling of the MILN, administering methylene blue (MB) dye intrauterinely or intradermally. Thirty-two bitches with tumors in different mammary glands were included in the study. In 13 bitches (GU group), the MILNs were stained with intrauterine MB, followed by unilateral lymphadenectomy, ovariohysterectomy (OVH) and unilateral mastectomy. Nineteen bitches (GI group) underwent OVH, followed by MILN staining with intradermal MB, lymphadenectomy, and unilateral mastectomy. In GU, 11 bitches (84.62%) exhibited MB-stained MILNs, but staining was not observed in two (15.38%). Metastasis to MILNs was observed in three bitches (9.38%) from the GI and two (6.25%) from the GU. Intrauterine and intradermal staining of MILNs in bitches with mammary tumors was efficient, but intradermal administration of MB produced better results. Given metastatic spread to MILNs in approximately 15.63% of patients, we recommend that screening for MILNs should be considered as part of the staging of animals with malignant mammary neoplasms.

A Multi-Center Retrospective Database Evaluation of Pediatric Subjects Diagnosed With Methemoglobinemia.

Methemoglobinemia requires early identification and treatment, but limited knowledge exists regarding the current therapeutic approach taken by clinicians as well as the outcomes that occur in children. To determine the current prevalence of this rare disease in the pediatric population, evaluate the impact of methemoglobin and functional hemoglobin levels, and assess how this disease is approached by clinicians. We hypothesize that methemoglobinemia prevalence is low and more methylene blue use would be observed in subjects with functional hemoglobin levels less than 7 g/dL. This was a retrospective observational cohort study utilizing deidentified TriNetX® electronic health record (EHR) data. Using a multicenter EHR database, we evaluated subjective characteristics, diagnostic, laboratory results, medication, and procedural codes. Ninety-eight children (mean age 5.3 ± 5.3 years) from 53 healthcare organizations were included. Methemoglobinemia prevalence was 0.0015% with an overall 30-day mortality of 6.1%. Subjects with methemoglobin percentages greater than 20% had a higher frequency of methylene blue administration (70.6% versus 24.7%, P = .0005). Critical care service requirements and methylene blue administration were similar in the subjects with functional hemoglobin less than 7 g/dL and more than 7 g/dL groups. Overall, 13 (13.2%) subjects underwent glucose-6-phosphate dehydrogenase deficiency (G6PD) testing. In our study, we found methemoglobinemia prevalence in children is low, there is a low frequency of G6PD testing despite methylene blue hemolysis risk, and subjects appeared to be treated similarly despite a low functional hemoglobin. These findings highlight the continued critical nature of this disease and may highlight opportunities for education aimed at improving care in children diagnosed with methemoglobinemia, particularly related to G6PD testing.

Dapsone Associated Methemoglobinemia-----A Case of Blue Discoloration:

Dapsone is among the medicine that belongs to sulfone groups and being used to treat leprosy and dermatitis. It inhibits the synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. This is a case of a lady in her mid70&amp;apos;s known case of pyoderma gangrenosum recently started on dapsonepresented to ED with complaint of shortness of breath, discoloration of fingers for 4days. Patient had saturation of 88% room air. Relevant examination showed blue discoloration of the finger pulps. Arterial blood gas analysis showed oxygen saturation of 98%RA and PaO2 of 87mmHg, suggestive of positive saturation gap. She was treated with IV methylene blue on the impression of methemoglobinemia and her discoloration improved rapidly. An approach to hypoxia in ED must be considered in context of saturation gap in patients suspected of having toxicological cause. Methemoglobinemia treatment requires methylene blue administration that causes rapid resolution of symptoms.

Exploring Methylene Blue and Its Derivatives in Alzheimer's Treatment: A Comprehensive Review of Randomized Control Trials.

Methylene blue (MB) and its compounds are investigated for their potential benefits in the management of Alzheimer's disease (AD). ADis a widely seen neuropathological disorder characterized by the gradual decline of cognitive abilities, ultimately leading to the development of severe dementia. It is anticipated that there will be a significant increase in the prevalence of ADdue to the agingpopulation. Histopathologically, AD is distinguished by the presence of intracellular tangles of neurofibrillary tissues (NFTs) and extracellular amyloid plaques within the brain. MB is a thiophenazine dye with FDA approval for treating several illnesses. Its ease in crossing the blood-brain barrier and potential therapeutic use in central nervous system diseases have increased interest in its application for treating AD. The literature review includes randomized clinical trials investigating MB's potential benefits in treating AD. The findings of the studies indicate that the administration of MB has demonstrated enhancements in cognitive function, reductions in the accumulation of plaques containing beta-amyloid, improvements in memory and cognitive function in animal subjects, and possesses antioxidant properties that can mitigate oxidative stress and inflammation within the brain. Thisreview evaluates the modern and latest research on the application of MB for treating AD.

Nonconvulsive Status Epilepticus and Encephalopathy Related to Ifosfamide - A Case Report

Introduction: Ifosfamide (IFX) is an alkylating drug used for chemotherapy to manage a wide range of malignancies including testicular, ovarian, head-and-neck cancers, lymphomas, and sarcomas. Central nervous system (CNS) toxicity is known to occur in 10%–40% of patients who are administered high doses of IFX. CNS toxicity includes an encephalopathy with underlying nonconvulsive status epilepticus manifesting with altered sensorium, mental confusion, seizures, ataxia, visual hallucinations, akinetic mute state extrapyramidal features, or coma. Case Report: We describe the case of a 65-year-old woman with a rapidly evolving confusional state and progressive decline in the fluency of speech progressing to mutism immediately after IFX chemotherapy. Results: Electroencephalogram (EEG) revealed evidence of nonconvulsive status epilepticus. The patient was managed with anticonvulsants, discontinuing IFX, and intravenous methylene blue infusion. Subsequently, the patient had significant improvement to an alert state with normalization of EEG abnormality. Conclusion: CNS toxicity following IFX usually manifests within 24 h of the drug administration, although clinical manifestations of toxicity may occur up to 4–6 days and a significant number of these patients may have a nonconvulsive status as the cause of the encephalopathy. Patients with encephalopathy following IFX should be evaluated with early EEG to assess for the presence or absence of a nonconvulsive status. Patients with a positive EEG would benefit from prompt and aggressive anticonvulsant therapy along with cessation of IFX therapy with or without intravenous methylene blue administration.

Hydroxocobalamin Versus Methylene Blue for the Treatment of Vasoplegic Shock Associated With Cardiopulmonary Bypass

To compare changes in vasopressor requirements and hemodynamic responses after hydroxocobalamin or methylene blue administration for vasoplegic shock (VS). Retrospective cohort analysis. Single-center, academic medical center. Cardiothoracic surgery adult patients. Hydroxocobalamin or methylene blue. The primary outcome was a change in vasopressor requirements over the first 24 hours (1, 3, 6, 12, and 24 hours) after hydroxocobalamin or methylene blue initiation. Secondary outcomes included changes in mean arterial pressure (MAP), systemic vascular resistance, and lactate. A total of 120 adult patients who received hydroxocobalamin (n=77) or methylene blue (n=43) were included. Vasopressor requirements at baseline were 0.34 µg/kg/min (95% CI 0.28-0.4) norepinephrine equivalent (NEE) in the hydroxocobalamin group, and 0.59 µg/kg/min (95% CI 0.52-0.66) NEE in the methylene blue group; p < 0.001. Vasopressor requirements decreased significantly at each time point within each group (hour 1 mean [95% CI] NEE, hydroxocobalamin 0.27 µg/kg/min [0.21-0.33]; methylene blue 0.44 µg/kg/min [0.38-0.51]; p < 0.001). The mean MAP at baseline was 65 mmHg (95% CI 63-67) in the hydroxocobalamin group, and 57 mmHg (95% CI 54-59) in the methylene blue group; p < 0.001. The mean MAP increased significantly from baseline at each time point within each group (hour 1 mean [95% CI] hydroxocobalamin 73 mmHg [71-75]; methylene blue 67 mmHg [65-70]; p < 0.001). After adjusting for baseline characteristics, a significantly greater reduction in vasopressor requirements and an increase in MAP were noted in the hydroxocobalamin group compared with the methylene blue group. Hydroxocobalamin was associated with a greater reduction in vasopressor requirements than methylene blue in treating VS associated with cardiopulmonary bypass.

Methylene blue reduces the serum levels of interleukin-6 and inhibits STAT3 activation in the brain and the skin of lipopolysaccharide-administered mice.

It is valuable to search for novel and economical agents for inhibiting STAT3 activation and blocking increases in IL-6 levels, due to the important roles of STAT3 and IL-6 in inflammation. Since Methylene Blue (MB) has shown therapeutical potential for multiple diseases, it has become increasingly important to investigate the mechanisms underlying the effects of MB on inflammation. Using a mouse model of lipopolysaccharide (LPS)-induced inflammation, we investigated the mechanisms underlying the effects of MB on inflammation, obtaining the following findings: First, MB administration attenuated the LPS-induced increases in the serum levels of IL-6; second, MB administration attenuated LPS-induced STAT3 activation of the brain; and third, MB administration attenuated LPS-induced STAT3 activation of the skin. Collectively, our study has suggested that MB administration can decrease the levels of IL-6 and STAT3 activation - two important factors in inflammation. Since MB is a clinically used and relatively economical drug, our findings have suggested therapeutic potential of MB for multiple inflammation-associated diseases due to its effects on STAT3 activation and IL-6 levels.

Spectroscopic study of methylene blue in vivo: effects on tissue oxygenation and tumor metabolism

Methylene blue (MB) is a promising photosensitizer (PS) for the treatment of pathological neoplasms, since it has both photodynamic activity (under laser irradiation) and redox and catalytic properties (in the absence of light). In the framework of this work, using spectroscopic methods, the effect of intravenous administration of MB on tissue oxygenation of hemoglobin in small animals in vivo in tumor and normal tissues was analyzed. The influence of MB on cell metabolism was analyzed. It has been shown that the use of MB promotes an increase in oxygen consumption by the tumor, and also leads to a shift in metabolism towards oxidative phosphorylation. It was shown that the use of MB contributes to an increase in oxygen consumption by the tumor, and also leads to a shift in metabolism towards oxidative phosphorylation.

Indoxacarb poisoning induced methemoglobinemia-a rare presentation in paediatric age group

Indoxacarb, an oxadiazine insecticide, has high insecticidal and low mammalian toxicity. The insecticidal activity of indoxacarb is attributed to its ability to block sodium channels in the insect nervous system. Several cases of indoxacarb-induced methemoglobinemia have been reported in adults, but presentation in paediatric age group is rare. Methaemoglobinaemia occurs after indoxacarb ingestion because its aromatic metabolites are biotransformed to active intermediates that produce methaemoglobin. The case involved is an adolescent girl who presented to the PICU 3 hours after suicidal ingestion of 10-15 ml of indoxacarb. After 15 min of consumption of poison she developed pain abdomen and vomiting. At PICU, she complained of nausea, vomiting and dizziness. Her vital signs were heart rate 96/min, BP 110/80 mmHg, oxygen saturation 78% on room air and GCS 15/15. Despite receiving 10L/ min of oxygen via NRBM mask. Her ECG showed normal sinus rhythm without ischaemic change, and CXR showed no specific abnormality. Initial arterial blood gas analysis revealed pH-7.413, pO2-123.6 mmHg, pCO2-37.7 mmHg, HCO3 23.5 mmol/L. Other laboratory results were normal. Methaemoglobinemia is a rare clinical presentation of indoxacarb poisoning. The treatment plan includes timely administration of injection methylene blue.

The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats.

Methylene Blue (MB) is a brain-penetrating drug with putative neuroprotective, antioxidant and metabolic enhancing effects. In vitro studies suggest that MB enhances mitochondrial complexes activity. However, no study has directly assessed the metabolic effects of MB in the human brain. We used in vivo neuroimaging to measure the effect of MB on cerebral blood flow (CBF) and brain metabolism in humans and in rats. Two doses of MB (0.5 and 1 mg/kg in humans; 2 and 4 mg/kg in rats; iv) induced reductions in global cerebral blood flow (CBF) in humans (F(1.74, 12.17)5.82, p = 0.02) and rats (F(1,5)26.04, p = 0.0038). Human cerebral metabolic rate of oxygen (CMRO2) was also significantly reduced (F(1.26, 8.84)8.01, p = 0.016), as was the rat cerebral metabolic rate of glucose (CMRglu) (t = 2.6(16) p = 0.018). This was contrary to our hypothesis that MB will increase CBF and energy metrics. Nevertheless, our results were reproducible across species and dose dependent. One possible explanation is that the concentrations used, although clinically relevant, reflect MB's hormetic effects, i.e., higher concentrations produce inhibitory rather than augmentation effects on metabolism. Additionally, here we used healthy volunteers and healthy rats with normal cerebral metabolism where MB's ability to enhance cerebral metabolism might be limited.