Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. As a medication, it is mainly used to treat methemoglobinemia by chemically reducing the ferric iron in hemoglobin to ferrous iron. Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy. It has previously been used for treating cyanide poisoning and urinary tract infections, but this use is no longer recommended.
Methylene blue is typically given by injection into a vein. Common side effects include headache, nausea, and vomiting. While use during pregnancy may harm the fetus, not using it in methemoglobinemia is likely more dangerous.
Methylene blue was first prepared in 1876, by Heinrich Caro. It is on the World Health Organization's List of Essential Medicines.
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InChI=1S/C16H18N3S.ClH/c1-18(2)11-5-7-13-15(9-11)20-16-10-12(19(3)4)6-8-14(16)17-13;/h5-10H,1-4H3;1H/q+1;/p-1 |
CXKWCBBOMKCUKX-UHFFFAOYSA-M |
[Cl-].CN(C)c1ccc2nc3ccc(cc3[s+]c2c1)N(C)C |
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antioxidant
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
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EC 1.4.3.4 (monoamine oxidase) inhibitor
An EC 1.4.3.* (oxidoreductase acting on donor CH-NH2 group, oxygen as acceptor) inhibitor that interferes with the action of monoamine oxidase (EC 1.4.3.4).
EC 3.1.1.8 (cholinesterase) inhibitor
An EC 3.1.1.* (carboxylic ester hydrolase) inhibitor that interferes with the action of cholinesterase (EC 3.1.1.8).
EC 4.6.1.2 (guanylate cyclase) inhibitor
An EC 4.6.* (P1O lyase) inhibitor that interferes with the action of enzyme guanylate cyclase (EC 4.6.1.2).
antimicrobial agent
A substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
antimalarial
A drug used in the treatment of malaria. Antimalarials are usually classified on the basis of their action against Plasmodia at different stages in their life cycle in the human.
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acid-base indicator
An acid or base which exhibits a colour change on neutralization by the basic or acidic titrant at or near the equivalence point of a titration.
fluorochrome
A fluorescent dye used to stain biological specimens.
antidepressant
Antidepressants are mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions.
cardioprotective agent
Any protective agent that is able to prevent damage to the heart.
histological dye
A dye used in microscopic or electron microscopic examination of cells and tissues to give contrast and to highlight particular features of interest, such as nuclei and cytoplasm.
neuroprotective agent
Any compound that can be used for the treatment of neurodegenerative disorders.
physical tracer
A physical tracer is one that is attached by physical means to the object being traced.
antimalarial
A drug used in the treatment of malaria. Antimalarials are usually classified on the basis of their action against Plasmodia at different stages in their life cycle in the human.
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View more via ChEBI Ontology
3,7-bis(dimethylamino)phenothiazin-5-ium chloride
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chlorure de méthylthioninium
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ChemIDplus
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cloruro de metiltioninio
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ChemIDplus
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methylthioninii chloridum
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ChemIDplus
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methylthioninium chloride
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ChemIDplus
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azul de metileno
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ChEBI
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Basic Blue 9
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ChemIDplus
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bleu de méthylène
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ChemIDplus
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C.I. 52015
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ChEBI
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Methylenblau
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ChemIDplus
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Methylene blue
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KEGG COMPOUND
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Methylene Blue anhydrous
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ChemIDplus
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Methylthioninium chloride
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KEGG COMPOUND
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Solvent blue 8
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ChEBI
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Swiss blue
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ChEBI
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3599847
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Reaxys Registry Number
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Reaxys
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61-73-4
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CAS Registry Number
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ChemIDplus
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Fang Q, Yan X, Li S, Sun Y, Xu L, Shi Z, Wu M, Lu Y, Dong L, Liu R, Yuan F, Yang SH (2016) Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study. Acta neurochirurgica. Supplement 121, 227-236 [PubMed:26463954] [show Abstract] The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke. In the present study, we evaluated the effects of MB on postischemic brain edema using magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Adult male rats were subjected to transient focal cerebral ischemia induced by 1 h middle cerebral artery occlusion (MCAO), followed by reperfusion. MB was infused intravenously immediately after reperfusion (3 mg/kg) and again at 3 h post-occlusion (1.5 mg/kg). Normal saline was administered as vehicle control. Sequential MRIs, including apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI), were obtained at 0.5, 2.5, and 48 h after the onset of stroke. Separated groups of animals were sacrificed at 2.5 and 48 h after stroke for ultrastructural analysis by TEM. In addition, final lesion volumes were analyzed by triphenyltetrazolium chloride (TTC) staining at 48 h after stroke. Ischemic stroke induced ADC lesion volume at 0.5 h during MCAOs that were temporally recovered at 1.5 h after reperfusion. No significant difference in ADC-defined lesion was observed between vehicle and MB treatment groups. At 48 h after stroke, MB significantly reduced ADC lesion and T2WI lesion volume and attenuated cerebral swelling. Consistently, MB treatment significantly decreased TTC-defined lesion volume at 48 h after stroke. TEM revealed remarkable swollen astrocytes, astrocytic perivascular end-feet, and concurrent shrunken neurons in the penumbra at 2.5 and 48 h after MCAO. MB treatment attenuated astrocyte swelling, the perivascular astrocytic foot process, and endothelium and also alleviated neuron degeneration. This study demonstrated that MB could decrease postischemic brain edema and provided additional evidence that future clinical investigation of MB for the treatment of ischemic stroke is warrented. | Makhadmeh GN, Abdul Aziz A, Abdul Razak K (2016) The efficacy of methylene blue encapsulated in silica nanoparticles compared to naked methylene blue for photodynamic applications. Artificial cells, nanomedicine, and biotechnology 44, 1018-1022 [PubMed:25707443] [show Abstract]
Background/aimsThis study analyzed the physical effects of methylene blue (MB) encapsulated within silica nanoparticles (SiNPs) in photodynamic therapy.Materials and methodsThe optimum concentration of MB needed to destroy red blood cells (RBCs) was determined, and the efficacy of encapsulated MB-SiNPs compared to that of naked MB was verified.ResultsThe results confirmed the applicability of MB encapsulated in SiNPs on RBCs, and established a relationship between the concentration of the SiNP-encapsulated MB and the time required to rupture 50% of the RBCs (t50).ConclusionThe MB encapsulated in SiNPs exhibited higher efficacy compared to that of naked MB. | Thiele T, Hron G, Kellner S, Wasner C, Westphal A, Warkentin TE, Greinacher A, Selleng K (2016) Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation. Blood transfusion = Trasfusione del sangue 14, 66-72 [PubMed:26192785] [show Abstract]
BackgroundMethylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway.Materials and methodsFifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7.ResultsThe velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations.DiscussionThe global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations. | Mohammed N, Grishkewich N, Waeijen HA, Berry RM, Tam KC (2016) Continuous flow adsorption of methylene blue by cellulose nanocrystal-alginate hydrogel beads in fixed bed columns. Carbohydrate polymers 136, 1194-1202 [PubMed:26572462] [show Abstract] The adsorption behavior of methylene blue by cellulose nanocrystal-alginate (CNC-ALG) hydrogel beads in a fixed bed column was studied by varying the initial dye concentrations, bed depths and flow rates. An unusual phenomenon was observed in the early phase of the adsorption, and the phenomenon was elucidated by varying other critical design parameters, such as the flow direction, diameter of column and composition of adsorbent. The swelling and shrinkage of hydrogel beads during the adsorption was responsible for the anomalous concentration versus time profile of the adsorption process. The maximum adsorption capacity of the column was 255.5mg/g, which is in agreement with the batch study determined from the Langmuir adsorption isotherm. A comprehensive understanding on the adsorption mechanism of CNC-ALG hydrogel beads during the early stages of adsorption was derived from this study. | Jang DH, Donovan S, Nelson LS, Bania TC, Hoffman RS, Chu J (2015) Efficacy of methylene blue in an experimental model of calcium channel blocker-induced shock. Annals of emergency medicine 65, 410-415 [PubMed:25441767] [show Abstract]
Study objectiveCalcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock.MethodsSprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test.ResultsOverall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to 124.1 minutes). Pulse rate and mean arterial pressure (MAP) differences between groups were analyzed until 60 minutes. Pulse rate was significantly higher in the methylene blue-treated group beginning 25 minutes after the start of the amlodipine infusion (95% CI 30 to 113 minutes) that was analyzed until 60 minutes. MAP was significantly higher in the methylene blue-treated group starting 25 minutes after the amlodipine infusion (95% CI 2 to 30 minutes) that was analyzed until 60 minutes.ConclusionMethylene blue did not result in a significant difference in mortality risk. There was an increased pulse rate, MAP, and median survival time in the methylene blue group. | De Crozals G, Farre C, Sigaud M, Fortgang P, Sanglar C, Chaix C (2015) Methylene blue phosphoramidite for DNA labelling. Chemical communications (Cambridge, England) 51, 4458-4461 [PubMed:25679473] [show Abstract] We report the first synthesis of a methylene blue (MB) phosphoramidite derivative suitable for DNA solid-phase synthesis. The electrochemical and optical properties of the resulting MB modified oligonucleotides were confirmed. This new molecule is an important breakthrough in the design of new probes labelled with MB. | Bae J, McNamara LE, Nael MA, Mahdi F, Doerksen RJ, Bidwell GL, Hammer NI, Jo S (2015) Nitroreductase-triggered activation of a novel caged fluorescent probe obtained from methylene blue. Chemical communications (Cambridge, England) 51, 12787-12790 [PubMed:26165999] [show Abstract] A near-infrared fluorescent probe based on methylene blue (p-NBMB) was developed for the detection of nitroreductase. Conjugating methylene blue with a p-nitrobenzyl moiety enables it to be activated by nitroreductase-catalyzed 1,6-elimination, resulting in the release of an active methylene blue fluorophore. | Kumar M, Tamilarasan R, Arthanareeswaran G, Ismail AF (2015) Optimization of methylene blue using Ca(2+) and Zn(2+) bio-polymer hydrogel beads: A comparative study. Ecotoxicology and environmental safety 121, 164-173 [PubMed:25913699] [show Abstract] Recently noted that the methylene blue cause severe central nervous system toxicity. It is essential to optimize the methylene blue from aqueous environment. In this study, a comparison of an optimization of methylene blue was investigated by using modified Ca(2+) and Zn(2+) bio-polymer hydrogel beads. A batch mode study was conducted using various parameters like time, dye concentration, bio-polymer dose, pH and process temperature. The isotherms, kinetics, diffusion and thermodynamic studies were performed for feasibility of the optimization process. Freundlich and Langmuir isotherm equations were used for the prediction of isotherm parameters and correlated with dimensionless separation factor (RL). Pseudo-first order and pseudo-second order Lagegren's kinetic equations were used for the correlation of kinetic parameters. Intraparticle diffusion model was employed for diffusion of the optimization process. The Fourier Transform Infrared Spectroscopy (FTIR) shows different absorbent peaks of Ca(2+) and Zn(2+) beads and the morphology of the bio-polymer material analyzed with Scanning Electron Microscope (SEM). The TG & DTA studies show that good thermal stability with less humidity without production of any non-degraded products. | Matos J, Montaña R, Rivero E (2015) Influence of activated carbon upon the photocatalytic degradation of methylene blue under UV-vis irradiation. Environmental science and pollution research international 22, 784-791 [PubMed:24788930] [show Abstract] Photodegradation of methylene blue (MB) was studied on TiO2 in the presence of activated carbon (AC) prepared from the sawdust of a soft wood by physical activation under CO2 flow, by pyrolysis under N2 flow, and by chemical activation with ZnCl2 and H3PO4 under N2 flow. MB photodegradation was performed under UV and UV-visible irradiation to verify the scaling-up of the present TiO2-AC binary materials. It was verified that oxygenated surface groups on carbon were intrinsically photoactive, and a synergy effect between both solids has been estimated from the first-order apparent rate constants in the photodegradation of MB. This effect enhances the photoactivity of TiO2 up to a factor of about 9 under visible irradiation, and it was associated to the surface properties of AC. | Zhang CY, Yu HL, Liu SH, Jiang G, Wang YJ (2015) Effect of lipiodol and methylene blue on the thoracoscopic preoperative positioning. International journal of clinical and experimental medicine 8, 7569-7576 [PubMed:26221301] [show Abstract] The aim of this study was to compare and analyze the site-specific accuracy of mixture of lipiodol and methylene blue (MLM) (0.6 ml, 1:5) and pure methylene blue (0.5 ml) on the rabbit lungs. In this study, CT-guided percutaneous injection of MLM and methylene blue. Compare the staining degree by biopsy of lung tissue. Use 4 points system to evaluate the site-specific accuracy at 6h and 24 h after injection. For MLM, evaluate its radiopacity by radiation. When evaluate the positioning, 2 points mean acceptable, 3 points mean excellent. The results indicated that the staining range of MLM is obvious less than that of methylene blue (0.6 vs. 1.0 cm, P<0.01), but the staining capacity of MLM is higher than that of methylene blue (2.8 vs. 2.2, P = 0.01). About the staining abilities which are evaluated as excellent, MLM group accounts for 81%, methylene blue group accounts for 38% (P = 0.011). About the radiopacity which are evaluated as acceptable or excellent, MLM group accounts for 62%. With good direct vision, the suitable positioning rate of MLM can be 100%, which is better than that of methylene blue. In conclusion, percutaneous injection of MLM can be used to lung positioning. The result shows that use MLM is better than only using methylene blue. But it is necessary to do the investigation in human beings in order to confirm the feasibility of its clinical application. | Church JT, Posluszny JA, Hemmila M, To KB, Cherry-Bukowiec JR, Waljee J (2015) Methylene blue for burn-induced vasoplegia: case report and review of literature. Journal of burn care & research : official publication of the American Burn Association 36, e107-11 [PubMed:25687361] [show Abstract] We report the use of a single dose of methylene blue in a patient with burn-induced vasoplegia refractory to fluids, vasopressors, and steroids. Administration of methylene blue allowed for cessation of epinephrine infusion within 2 hours of administration, and reduction in excessive fluid resuscitation. The patient's clinical course continued for 2 months and was complicated by severe acute respiratory distress syndrome, pneumonia, septic shock, poor skin graft adherence, renal failure requiring continuous renal replacement therapy, cutaneous mucormycosis, and ultimately, withdrawal of care and death. Despite the eventual outcome, this is the longest reported survival following methylene blue administration for vasoplegia secondary to burn injury. | Larson KJ, Wittwer ED, Nicholson WT, Weingarten TN, Price DL, Sprung J (2015) Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy. Journal of clinical anesthesia 27, 247-251 [PubMed:25499271] [show Abstract] Serotonin released in the nerve synapses is cleared through reuptake into presynaptic neurons and metabolism with monoamine oxidase (MAO). Therapy with selective serotonin reuptake inhibitors (SSRIs) or MAO inhibitors increases serotonin concentration in the synaptic cleft and may result in serotonin syndrome (SS). Our patient undergoing sentinel lymph node biopsy was on fluoxetine (SSRI) and intraoperatively developed SS after receiving fentanyl (200 μg) and methylene blue (MAO inhibitor), 7 mg subcutaneously into the scalp. Initial presentation was several episodes of generalized muscle activity, which was later diagnosed as lower extremity myoclonus consistent with SS. Upon awakening, the patient showed no evidence of encephalopathy, and the clonus was less intense. The patient was discharge home the next day. Our case suggests the possibility that even a small dose of methylene blue, when administered simultaneously with other serotoninergic medications, may be associated with serotonin toxicity. | Liu X, Yang Y, Shi X, Li K (2015) Fast photocatalytic degradation of methylene blue dye using a low-power diode laser. Journal of hazardous materials 283, 267-275 [PubMed:25285998] [show Abstract] This study focused on the application of diode lasers as alternative light sources for the fast photocatalytic degradation of methylene blue. The photocatalytic decomposition of methylene blue in aqueous solution under 443 nm laser light irradiation was found to be technically feasible using Ag/AgCl nanoparticles as photocatalysts. The effects of various experimental parameters, such as irradiation time, light source, catalyst loading, initial dye concentration, pH, and laser energy on decolorization and degradation were investigated. The mineralization of methylene blue was confirmed by chemical oxygen demand analysis. The results demonstrate that the laser-induced photocatalytic process can effectively degrade methylene blue under the optimum conditions (pH 9.63, 4 mg/L MB concentration, and 1.4 g/L Ag/AgCl nanoparticles). | Laes JR, Williams DM, Cole JB (2015) Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report. Journal of medical toxicology : official journal of the American College of Medical Toxicology 11, 460-463 [PubMed:26310944] [show Abstract]
IntroductionThe purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient.Case reportThis is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg.DiscussionMethylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies. | Miclescu AA, Svahn M, Gordh TE (2015) Evaluation of the protein biomarkers and the analgesic response to systemic methylene blue in patients with refractory neuropathic pain: a double-blind, controlled study. Journal of pain research 8, 387-397 [PubMed:26213475] [show Abstract]
AimThis study was carried out in patients with neuropathic pain in order to assess the analgesic effects and changes in protein biomarkers after the administration of methylene blue (MB), a diaminophenothiazine with antioxidant and anti-inflammatory properties, and with inhibitory effects on nitric oxide.Materials and methodsTen patients with chronic refractory neuropathic pain were randomized to receive either MB (10 mg/mL Methylthioninium chloride) 2 mg/kg (MB group) or MB 0.02 mg/kg (control group) infused over 60 minutes. Sensory function and pain (Numerical Rating Scale) were evaluated at baseline and at 60 minutes after the start of the infusion. The patients kept a pain diary during the next 24 hours and for the following 4 days. Plasma and urinary concentrations of 8-isoprostane-prostaglandin F2α (8-iso-PGF2α) and plasma protein biomarkers prior to and after the infusions were measured with radioimmunoassay and with proximity extension assay.ResultsA decrease of the Numerical Rating Scale at 60 minutes in comparison with baseline was observed in the MB (P=0.047) group. The decrease was significant between the MB and the control group on the day of and day after MB infusion (P=0.04 and P=0.008, respectively). There was no difference in systemic protein expressions between groups except for prolactin (PRL) (P=0.02). Three patients demonstrated diminished dynamic mechanical allodynia.ConclusionMB decreased the pain levels in patients with chronic therapy-resistant neuropathic pain on the first 2 days after administration. Known as an endocrine modulator on the anterior pituitary gland, MB infusion produced a decrease of PRL. The detailed role of PRL effects in chronic neuropathic pain remains undetermined. | Smith CJ, Wang D, Sgambelluri A, Kramer RS, Gagnon DJ (2015) Serotonin syndrome following methylene blue administration during cardiothoracic surgery. Journal of pharmacy practice 28, 207-211 [PubMed:25613051] [show Abstract]
IntroductionDespite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient.Case reportA 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home.DiscussionOnly 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome. | Shou-wang C, Shi-zhong Y, Wen-ping L, Geng C, Wan-qing G, Wei-dong D, Wei-yi W, Zhi-qiang H, Jia-hong D (2015) Sustained methylene blue staining to guide anatomic hepatectomy for hepatocellular carcinoma: Initial experience and technical details. Surgery 158, 121-127 [PubMed:25791029] [show Abstract]
BackgroundThe boundary of the target hepatic segment within the liver parenchyma cannot be marked by the use of a conventional anatomic hepatectomy approach. This study describes a novel methylene blue staining technique for guiding the anatomic resection of hepatocellular carcinoma (HCC).MethodsBetween February 2009 and February 2012, anatomic hepatectomy was performed in 106 patients with HCC via a novel, sustained methylene blue staining technique. Sustained staining was achieved by injecting methylene blue into the distal aspect of the portal vein after exposing Glisson's sheath. The hepatic pedicle was immediately ligated, and the hepatic parenchymal transection was performed along the interface between methylene blue stained tissue and unstained tissue.ResultsAnatomic hepatectomies included subsegmentectomy (n = 16), monosegmentectomy (n = 57), multisegmentectomy (n = 27), and hemihepatectomy (n = 6). The portal vein was injected successfully with methylene blue in 100% of cases, and complete staining of the target hepatic segment was achieved in 98 of 106 (92.5%) cases. Mean intraoperative bleeding was 360 ± 90 mL, and the postoperative complication rate was 24.5% (26/106). No perioperative mortality occurred. Operative margins were all negative on pathologic examination. Mean duration of postoperative follow-up was 40 months (range, 24-60). No local recurrence (around the operative margin) occurred.ConclusionThis novel technique of achieving sustained staining by injecting methylene blue then immediately ligating the hepatic pedicle is simple and feasible. It can guide the selection of the operative margin during hepatic parenchyma transection to improve the accuracy of anatomic hepatectomy for the treatment of HCC. | Aoyama T, Fujikawa H, Cho H, Ogata T, Shirai J, Hayashi T, Rino Y, Masuda M, Oba MS, Morita S, Yoshikawa T (2015) A methylene blue-assisted technique for harvesting lymph nodes after radical surgery for gastric cancer: a prospective, randomized, controlled study. The American journal of surgical pathology 39, 266-273 [PubMed:25356528] [show Abstract] Harvesting lymph nodes (LNs) after gastrectomy is essential for accurate staging. This trial evaluated the efficiency and quality of a conventional method and a methylene blue-assisted method in a randomized manner. The key eligibility criteria were as follows: (i) histologically proven adenocarcinoma of the stomach; (ii) clinical stage I-III; (iii) R0 resection planned by gastrectomy with D1+ or D2 lymphadenectomy. The primary endpoint was the ratio of the pathologic number of harvested LNs per time (minutes) as an efficacy measure. The secondary endpoint was the number of harvested LNs, as a quality measure. Between August 2012 and December 2012, 60 patients were assigned to undergo treatment using the conventional method (n=29) and the methylene blue dye method (n=31). The baseline demographics were mostly well balanced between the 2 groups. The number of harvested LNs (mean±SD) was 33.6±11.9 in the conventional arm and 43.4±13.9 in the methylene blue arm (P=0.005). The ratio of the number of the harvested LNs per time was 1.12±0.46 LNs/min in the conventional arm and 1.49±0.59 LNs/min in the methylene blue arm (P=0.010). In the subgroup analyses, the quality and efficacy were both superior for the methylene blue dye method compared with the conventional method. The methylene blue technique is recommended for harvesting LNs during gastric cancer surgery on the basis of both the quality and efficacy. | Zhang Z, Liao Y, Ai B, Liu C (2015) Methylene blue staining: a new technique for identifying intersegmental planes in anatomic segmentectomy. The Annals of thoracic surgery 99, 238-242 [PubMed:25440279] [show Abstract]
BackgroundPulmonary segmentectomy is being increasingly used to resect small lung nodules; however, identifying the intersegmental plane is difficult. We describe a new methylene blue staining technique that we developed to identify the intersegmental planes in anatomic segmentectomy using video-assisted thoracic surgery (VATS) or thoracotomy and to evaluate its feasibility and safety.MethodsBetween October 2013 and December 2013, 14 consecutive patients with lung disease underwent anatomic segmentectomy at our institution (10 VATS, 4 conventional thoracotomy). Methylene blue 0.1% (20 mL) was slowly injected into the bronchus of the target pulmonary segments using an intravenous needle after division of the artery, vein, and bronchus of the target segments, and the boundaries were detected, followed by anatomic segmentectomy.ResultsThe staining took only 3 min. The target pulmonary segments stained blue, allowing for the clear identification of the intersegmental plane on both the surface and in the lung parenchyma, and all operations were successfully completed. Staining did not affect pathologic examination of the resected specimens. The fluid that drained from the chest tube and the patients' sputum, urine, and feces were not blue. There were no perioperative deaths or major complications.ConclusionsTo our knowledge, this study is the first to report a safe and feasible methylene blue staining method for identifying the lung segment borders that does not require any special equipment. More importantly, this method can clearly detect the intersegmental planes on the pleural surface and within the lung parenchyma, enabling thoracic surgeons to accurately perform anatomic segmentectomy. | Suwanarusk R, Russell B, Ong A, Sriprawat K, Chu CS, PyaePhyo A, Malleret B, Nosten F, Renia L (2015) Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance. The Journal of antimicrobial chemotherapy 70, 124-129 [PubMed:25150147] [show Abstract]
ObjectivesMethylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine.MethodsTo do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser.ResultsP. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule.ConclusionsOur data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria. | Yu JX, Li BH, Sun XM, Yuan J, Chi RA (2010) Poly(amic acid)-modified biomass of baker's yeast for enhancement adsorption of methylene blue and basic magenta. Applied biochemistry and biotechnology 160, 1394-1406 [PubMed:19277479] [show Abstract] In this study, poly(amic acid)-modified biomass was prepared to improve the adsorption capacities for two cationic dyes, methylene blue and basic magenta. X-ray photoelectron spectroscopy and potentiometric titration demonstrated that a large number of imide, amine, and carboxyl groups were introduced on the biomass surface, and the concentrations of these functional groups were calculated to be 0.27, 1.08, and 1.08 mmol g(-1) by using the first derivative method. According to the Langmuir equation, the maximum uptake capacities (q(m)) for methylene blue and basic magenta were 680.3 and 353.4 mg g(-1), respectively, which were 13- and sevenfold than that obtained on the unmodified biomass. Adsorption kinetics study showed that the completion of the adsorption process needed only 40 min, which is faster than the common sorbent such as activated carbon and resin. Experimental results showed that pH and ionic strength had little effect on the capacity of the modified biomass, indicating that the modified biomass had good potential for practical use. | Nakayama M, Nakamoto S, Iida C, Yoshimoto M (2009) Removal of methylene blue from aqueous solution using a polarizable nanolayered manganese oxide film. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 25, 229-233 [PubMed:19212058] [show Abstract] A layered manganese oxide film grown electrochemically was applied to remove methylene blue (MB), a cationic dye, from an aqueous solution. A layered MnO(x) film intercalated with tetraethylammonium (Et(4)N) cations was deposited potentiostatically at +1.0 V (vs. Ag/AgCl) from an aqueous Mn(2+) solution containing Et(4)NCl. Et(4)N cations were sandwiched between negatively charged MnO(x) layers. When the Et(4)N/MnO(x) film was immersed in a solution containing MB alone, the intercalated Et(4)N cations were replaced with MB in a solution phase by an ion-exchange mechanism. The uptake capacity of the Et(4)N/MnO(x) film for MB was estimated to be 45.3 mg per 1.0 g of MnO(2). In the presence of KCl, the MB sorption was seriously restricted because the interlayer space was occupied by K(+) ions. However, the MnO(x) film anodized at +0.8 V can selectively take up MB molecules from the KCl solution. This can be ascribed to an increase in the interlayer space available to the sorption of MB due to the extraction of K(+) ions, where the MnO(x) surface probably has a specific affinity toward MB molecules. | Zolfaghari PS, Packer S, Singer M, Nair SP, Bennett J, Street C, Wilson M (2009) In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent. BMC microbiology 9, 27 [PubMed:19193212] [show Abstract]
BackgroundThe widespread problem of antibiotic resistance in pathogens such as Staphylococcus aureus has prompted the search for new antimicrobial approaches. In this study we report for the first time the use of a light-activated antimicrobial agent, methylene blue, to kill an epidemic methicillin-resistant Staphylococcus aureus (EMRSA-16) strain in two mouse wound models.ResultsFollowing irradiation of wounds with 360 J/cm(2) of laser light (670 nm) in the presence of 100 microg/ml of methylene blue, a 25-fold reduction in the number of viable EMRSA was seen. This was independent of the increase in temperature of the wounds associated with the treatment. Histological examination of the wounds revealed no difference between the photodynamic therapy (PDT)-treated wounds and the untreated wounds, all of which showed the same degree of inflammatory infiltration at 24 hours.ConclusionThe results of this study demonstrate that PDT is effective at reducing the total number of viable EMRSA in a wound. This approach has promise as a means of treating wound infections caused by antibiotic-resistant microbes as well as for the elimination of such organisms from carriage sites. | Bujdák J, Jureceková J, Bujdákova H, Lang K, Sersen F (2009) Clay mineral particles as effficient carriers of methylene blue used for antimicrobial treatment. Environmental science & technology 43, 6202-6207 [PubMed:19746714] [show Abstract] There is a strong demand to identify new strategies for disinfection and treatment of human, animal, and plant pathogens. The presented work shows the potential of clay minerals to contribute to the development of novel disinfection materials. Enhanced antimicrobial effect of a photoactive organic dye, methylene blue (MB), in the colloids of clay mineral was observed. Singlet oxygen (1O2) formed upon visible light irradiation was detected directly using luminescence measurements atthe near-infrared region and by spin-trapping method. While MB adsorbed on clay colloid particles lost the ability to produce 1O2 due to molecular aggregation, surprisingly, the antimicrobial activity was significantly enhanced. Under visible light irradiation, MB/clay minerals dispersions prevented the sporulation of A. niger and Penicillium sp. and inhibited the growth of C. albicans by an additional 6-15% when compared with MB solution. In the experiments with E. coli, the efficiency of MB was increased by the reduction of surviving cells by 27 and 33%. S. aureus proved to be the most susceptible to MB/clay dispersions. Only less than 20% cells survived with respect to the control experiment at the low MB concentration (1.1 x 10(-6) mol dm(-3)). The contradiction between the significant antimicrobial properties of MB in clay colloidal systems and low 1O2 formation can be explained in terms of the photosensitization mechanism. The role of clay particles is most likely to promote the contact between microorganism cells and photoactive MB. Although the dye directly bound to the clay surface exhibits significantly reduced photoactivity, the presence of clay mediates the delivery of dye molecules on the surface or inside cells. The results indicate new perspectives of potential implementations of clay minerals as parts of complex disinfection materials for industrial applications or in understanding similar processes in nature. | Rojas JC, Simola N, Kermath BA, Kane JR, Schallert T, Gonzalez-Lima F (2009) Striatal neuroprotection with methylene blue. Neuroscience 163, 877-889 [PubMed:19596056] [show Abstract] Recent literature indicates that low-dose Methylene Blue (MB), an autoxidizable dye with powerful antioxidant and metabolic enhancing properties, might prevent neurotoxin-induced neural damage and associated functional deficits. This study evaluated whether local MB may counteract the anatomical and functional effects of the intrastriatal infusion of the neurotoxin rotenone (Rot) in the rat. To this end, stereological analyses of striatal lesion volumes were performed and changes in oxidative energy metabolism in the striatum and related motor regions were mapped using cytochrome oxidase histochemistry. The influence of MB on striatal levels of oxidative stress induced by Rot was determined, and behavioral tests were used to investigate the effect of unilateral MB coadministration on motor asymmetry. Rot induced large anatomical lesions resembling "metabolic strokes," whose size was greatly reduced in MB-treated rats. Moreover, MB prevented the decrease in cytochrome oxidase activity and the perilesional increase in oxidative stress associated with Rot infusion in the striatum. MB also prevented the indirect effects of the Rot-induced lesion on cytochrome oxidase activity in related motor regions, such as the striatal regions rostral and caudal to the lesion, the substantia nigra compacta and reticulata, and the pedunculopontine nucleus. At a network level, MB maintained a global strengthening of functional connectivity in basal ganglia-thalamocortical motor circuits, as opposed to the functional decoupling observed in Rot-alone subjects. Finally, MB partially prevented the behavioral sensorimotor asymmetries elicited by Rot. These results are consistent with protective effects of MB against neurotoxic damage in the brain parenchyma. This study provides the first demonstration of the anatomical, metabolic and behavioral neuroprotective effects of MB in the striatum in vivo, and supports the notion that MB could be a valuable intervention against neural damage associated with oxidative stress and energy hypometabolism. | Shen JS, Yu T, Xie JW, Jiang YB (2009) Photoluminescence of CdTe nanocrystals modulated by methylene blue and DNA. A label-free luminescent signaling nanohybrid platform. Physical chemistry chemical physics : PCCP 11, 5062-5069 [PubMed:19562136] [show Abstract] A nanohybrid consisting of water-soluble thioglycolic acid (TGA)-capped CdTe nanocrystals (NCs) and methylene blue (MB) was designed as a label-free luminescent signaling platform for DNA. This sensing system was identified to operate under the photoinduced electron transfer (PET) mechanism in which MB is the electron acceptor and the binding site for the designated target molecule DNA. We showed that MB bound with TGA-capped CdTe NCs via strong electrostatic interactions resulted in an efficient quenching of the photoluminescence (PL) of NCs. Steady-state and time-resolved PL, and electron paramagnetic resonance (EPR) experiments established the quenching pathway of PET from the conduction band (CB) of NCs to the ground state of MB. In the presence of the target molecule DNA, the MB-quenched PL of NCs could be reversibly restored by double-stranded DNA as the PET pathway is blocked when MB is taken away from the NCs surface due to its intercalation into, and electrostatic interaction with, DNA. The platform was successfully applied for sensing DNA and signaling DNA hybridization by switching the PET process. Such a nanohybrid represents a robust PET luminescent nanosensor that is, in principle, applicable for other species by employing suitable electron acceptors as binding sites. | Sobal G, Rodrigues M, Sinzinger H (2008) Radioiodinated methylene blue--a promising agent for melanoma scintigraphy: labelling, stability and in vitro uptake by melanoma cells. Anticancer research 28, 3691-3696 [PubMed:19189650] [show Abstract] Melanoma is a tumor of continuously increasing incidence for which new methods of imaging and targeted therapy are widely sought. Radioiodinated methylene blue is a promising tracer, showing selective uptake in human pigmented melanoma cells. We performed 131I-labeling of the tracer using 1% methylene blue injection United States Pharmacopeia (USP) and 131I sodium iodide. For quality control, a Merck high performance liquid chromatography (HPLC) system was used. We developed a new HPLC procedure using 0.1% trifluoroacetic acid, 90% acetonitrile and 10% water as solvent for isocratic elution of the tracer and applied a TLC method using ITLC-SG strips and the same solvent. The stability of the preparation was studied for 15 min, 3 h and 6 h. In order to evaluate the potential relevance of 131I-labeled methylene blue for melanoma detection, the in vitro uptake of 131I-methylene blue was investigated in SK-MEL 28 and 518A2 melanoma cells. Time and a temperature influence on uptake of 1311 methylene blue by these two melanoma cells were investigated. The radiochemical purity obtained by the HPLC method was 99.97 +/- 0.08% (n=8), while that by the TLC method was 99.88 +/- 0.16% (n=8). This indicates the excellent agreement between these two methods. The stability was persistent over 6 h and amounted to 99.75% +/- 0.21% (n=8). The uptake of 131I methylene blue was time and temperature dependent by both melanoma cells lines. The net cellular uptake on incubation at 37 degrees C of 131I methylene blue by SK-MEL 28 cells was high at 56.3-61.8% and that by 518A2-cells was 36.3-56.0%. Uptake by these cells was also investigated at 22 degrees C. The uptake by both cell types was also high at this temperature, but lower than that at 37 degrees C, amounting to 45.0-51.7% and 25.6-36.3%, respectively. Due to its easy handling and quite high uptake by melanoma cells, we expect that this tracer could be successfully used in routine application for melanoma imaging or eventual radiotherapy. | Pavan FA, Mazzocato AC, Gushikem Y (2008) Removal of methylene blue dye from aqueous solutions by adsorption using yellow passion fruit peel as adsorbent. Bioresource technology 99, 3162-3165 [PubMed:17692516] [show Abstract] The removal of color from aquatic systems caused by presence of synthetic dyes is extremely important from the environmental viewpoint because most of these dyes are toxic, mutagenic and carcinogenic. In this present study, the yellow passion fruit (Passiflora edulis Sims. f. flavicarpa Degener) peel a powdered solid waste, was tested as an alternative low-cost adsorbent for the removal of a basic dye, methylene blue (MB), from aqueous solutions. Adsorption of MB onto this natural adsorbent was studied by batch adsorption isotherms at room temperature. The effects of shaking time and pH on adsorption capacity were studied. An alkaline pH was favorable for the adsorption of MB. The contact time required to obtain the maximum adsorption was 56 h at 25 degrees C. Yellow passion fruit peel may be used as an alternative adsorbent to remove MB from aqueous solutions. | Lu Y, Jiao R, Chen X, Zhong J, Ji J, Shen P (2008) Methylene blue-mediated photodynamic therapy induces mitochondria-dependent apoptosis in HeLa cell. Journal of cellular biochemistry 105, 1451-1460 [PubMed:18980251] [show Abstract] Methylene blue (MB), a widely studied reagent, is investigated in this work for its usage in photodynamic therapy (PDT). PDT has been proved to be highly effective in the treatment of different types of cancers. Previous studies showed MB has both high affinity for mitochondria and high photodynamic efficiency. To elucidate the effects of MB in PDT, we analyzed PDT-induced apoptosis in HeLa cells by introducing different doses of MB into the culture media. Our data showed that MB-mediated PDT triggered intense apoptotic cell death through a series of steps, beginning with photochemical generation of reactive oxygen species. The release of cytochrome c and activation of caspase-3 indicated that MB-PDT-mediated apoptosis in HeLa cells was executed by the mitochondria-dependent apoptotic pathway. Importantly, proteomic studies confirmed that expression levels of several mitochondrial proteins were altered in MB-PDT-induced apoptosis, including TRAP1, mitochondrial elongation factor Tu and peroxiredoxin 3 isoform b. Western blot data showed that phosphorylation of ERK1/2 and PKA were reduced in MB-PDT treated cells, indicating several signal molecules participating in this apoptotic cascade. Moreover, MB-PDT induced an increase in the strength of interaction between Bcl-xL and dephosphorylated Bad. This led to loss of the pro-survival function of Bcl-xL and resulted in mitochondria-mediated apoptosis. This study provides solid evidence of a strong induction by MB-PDT of a mitochondria-dependent apoptosis cascade in HeLa cells. | Pavan FA, Lima EC, Dias SL, Mazzocato AC (2008) Methylene blue biosorption from aqueous solutions by yellow passion fruit waste. Journal of hazardous materials 150, 703-712 [PubMed:17597293] [show Abstract] The yellow passion fruit (Passiflora edulis Sims. f. flavicarpa Degener) (YPFW) a powdered solid waste, was tested as biosorbent for the removal of a cationic dye, methylene blue (MB), from aqueous solutions. Adsorption of MB onto this low-cost natural adsorbent was studied by batch adsorption at 25 degrees C. The effects of shaking time, biosorbent dosage and pH on adsorption capacity were studied. In alkaline pH region the adsorption of MB was favorable. The contact time required to obtain the maximum adsorption was 48 h at 25 degrees C. Four kinetic models were tested, being the adsorption kinetics better fitted to pseudo-first order and ion exchange kinetic models. The ion exchange and pseudo-first order constant rates were 0.05594 and 0.05455 h(-1), respectively. The equilibrium data were fitted to Langmuir, Freundlich, Sips and Redlich-Peterson isotherm models. Taking into account the analysis of the normal distribution of the residuals (difference of q(measured)-q(model)), the data were best fitted to Sips isotherm model. The maximum amount of MB adsorbed on YPFW biosorbent was 44.70 mg g(-1). | Evora PR, Simon MR (2007) Role of nitric oxide production in anaphylaxis and its relevance for the treatment of anaphylactic hypotension with methylene blue. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 99, 306-313 [PubMed:17941276] [show Abstract]
ObjectiveTo review the role of nitric oxide production in anaphylaxis.Data sourcesWe performed MEDLINE searches of the literature. In addition, some references known to the authors but not listed in MEDLINE, such as abstracts and a CD-ROM, were included. Finally, additional clinical details of the cases were provided by one of the authors.Study selectionPrimary reports were preferentially selected for inclusion. However, some secondary publications are also cited.ResultsHistamine along with other mediators, such as leukotrienes, tumor necrosis factor, and platelet-activating factor, induce the production of nitric oxide. Nitric oxide can inhibit the release and effects of catecholamines. Sympathetic amines may inhibit production of nitric oxide. Studies in animals have demonstrated the generation of nitric oxide during anaphylaxis. Inhibition of nitric oxide synthase improves survival in an animal model of anaphylaxis. Nitric oxide causes vasodilation indirectly by increasing the activation of guanylyl cyclase, which then causes smooth muscle relaxation by increasing the concentration of smooth muscle cyclic guanosine monophosphate. Methylene blue is an inhibitor of guanylyl cyclase, which increases systemic vascular resistance and reverses shock in animal studies. The previously reported successful treatment with methylene blue of 11 patients with anaphylactic hypotension is reviewed.ConclusionNitric oxide plays a significant role in the pathophysiology of anaphylaxis. Treatment with methylene blue should be considered in patients with anaphylactic hypotension that has not responded to other interventions. | Ramsay RR, Dunford C, Gillman PK (2007) Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. British journal of pharmacology 152, 946-951 [PubMed:17721552] [show Abstract]
Background and purposeMonoamine oxidase inhibitors (MAOI) are known to cause serotonin toxicity (ST) when administered with selective serotonin reuptake inhibitors (SSRI). Methylene blue (methylthionium chloride, MB), a redox dye in clinical use, has been reported to precipitate ST in patients using SSRI. MB was assessed for MAO inhibition and so for its potential to precipitate ST.Experimental approachInhibition of purified human MAO was quantified using kinetic assays and visible spectral changes to study the interactions of MB with MAO A.Key resultsMB was a potent (tight binding) inhibitor for MAO A. It also inhibited MAO B but at much higher concentration. Interactions of MB with the active site of MAO A were confirmed by its action both as an oxidising substrate and as a one-electron reductant.Conclusions and implicationsMB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally. At concentrations reported in the literature after intravenous administration, MAO B would be partially inhibited but MAO A would be completely inhibited. This inhibition of MAO A would be expected to lead to perturbations of 5-hydroxytryptamine metabolism and hence account for ST occurring when administered to patients on SSRI treatment. | Yuan SH, Xiong Y, Wei M, Yan XJ, Zhang HZ, Zeng YX, Liang LZ (2007) Sentinel lymph node detection using methylene blue in patients with early stage cervical cancer. Gynecologic oncology 106, 147-152 [PubMed:17499345] [show Abstract]
ObjectiveTo evaluate the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer using the low-cost methylene blue dye and to optimize the application procedure.Patients and methodsPatients with stage Ib(1)-IIa cervical cancer and subjected to abdominal radical abdominal hysterectomy and pelvic lymphadenectomy were enrolled. Methylene blue, 2-4 ml, was injected into the cervical peritumoral area in 77 cases (4 ml patent blue in the other four cases) 10-360 min before the incision, and surgically removed lymph nodes were examined for the blue lymph nodes that were considered as SLNs.ResultsHigh SLN detection rate was successfully achieved when 4 ml of methylene blue was applied (93.9%, 46/49). Bilaterally SLN detection rate was significantly higher (78.1% vs. 47.1% P=0.027) in cases when the timing of application was more than 60 min before surgery than those with timing no more than 30 min. The blue color of methylene blue-stained SLNs sustained both in vivo and ex vivo, compared with the gradually faded blue color of patent blue that detected in 3 of 4 cases unilaterally. In the total of 112 dissected sides, the most common location of SLNs was the obturator basin (65.2%, 73/112), followed by external iliac area (30.4%, 34/112) and internal iliac area (26.8%, 30/112). Three patients who gave false negative results all had enlarged nodes.ConclusionMethylene blue is an effective tracer to detect SLNs in patients with early stage cervical cancer. The ideal dose and timing of methylene blue application are 4 ml and 60-90 min prior surgery, respectively. | Garavito G, Bertani S, Rincon J, Maurel S, Monje MC, Landau I, Valentin A, Deharo E (2007) Blood schizontocidal activity of methylene blue in combination with antimalarials against Plasmodium falciparum. Parasite (Paris, France) 14, 135-140 [PubMed:17645185] [show Abstract] Methylene blue (MB) is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC) method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy. | Heydrick SJ, Reed KL, Cohen PA, Aarons CB, Gower AC, Becker JM, Stucchi AF (2007) Intraperitoneal administration of methylene blue attenuates oxidative stress, increases peritoneal fibrinolysis, and inhibits intraabdominal adhesion formation. The Journal of surgical research 143, 311-319 [PubMed:17826794] [show Abstract]
BackgroundMounting evidence indicates that postoperative oxidative stress may be linked to decreased fibrinolytic activity and, subsequently, the development of intraabdominal adhesions. The goal of this study was to determine if methylene blue, a highly redox active dye that has been shown to inhibit adhesion formation (1) acts as an antioxidant in the postoperative peritoneum, and (2) subsequently affects fibrinolytic activity.Materials and methodsIntraabdominal adhesions were surgically induced in rats receiving methylene blue (30 mg/kg) or vehicle (sterile water) intraperitoneally at surgery. At 24 h and 7 d following surgery, adhesion formation, oxidative stress, and peritoneal fibrinolytic activity were assessed.ResultsMethylene blue did not affect adhesion formation at 24 h, but did induce a >50% regression in adhesions after 7 d (P < 0.05). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO) activities, and 8-isoprostane and thiobarbituric acid-reactive substances were all significantly increased in peritoneal tissue samples (P < 0.05) by 24 h following surgery. Methylene blue inhibited NADPH oxidase by 98% and MPO activity by 78% in the 24 h tissue samples, and blunted the corresponding surgery-induced increases in tissue lipid and protein oxidation. Furthermore, methylene blue significantly increased (P < 0.05) fibrinolytic activity in peritoneal fluid at 24 h.ConclusionsMethylene blue acts as an antioxidant in this experimental system and may reduce intraabdominal adhesion formation by enhancing peritoneal fibrinolytic activity following surgery. | Tsuchiya T, Takeuchi T, Hayashida K, Shimizu H, Ando K, Harada E (2006) Milk-derived lactoferrin may block tolerance to morphine analgesia. Brain research 1068, 102-108 [PubMed:16380099] [show Abstract] Lactoferrin (LF) is a multifunctional protein that is widely found in milk, blood, and other biological fluids. In the present study, we investigated the possibility that LF may block a tolerance to morphine-induced analgesia in the mouse. The nociceptive effect of bovine milk-derived LF (bLF) was estimated in the mouse tail-flick test. Although an intraperitoneal (100 mg/kg) or an oral (300 mg/kg) administration of bLF did not show remarkable analgesia, a combination with intraperitoneal administration of morphine (3 mg/kg) strikingly enhanced morphine-induced analgesia. Moreover, repeated administration of morphine at doses of 3 mg/kg (ip) or 5 mg/kg (ip) caused a tolerance to the morphine on the 5th or 7th day, respectively. In contrast, the combination of bLF (100 mg/kg, ip) with morphine (3 mg/kg, ip) retarded the development of tolerance to the 9th day, although bLF did not show any effect on the mice that had obtained tolerance to morphine. Furthermore, the potentiative effect of bLF was partially blocked by pre-treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and completely blocked by 7-nitroindazole (7-NI), a selective neuronal NOS (nNOS) inhibitor. Methylene blue (MB), a guanylate cyclase (GC) inhibitor, also dose-dependently prevented the potentiative effect of bLF. These results suggest that bLF selectively activates nNOS and then accelerates NO production. The increased NO in turn modulates the GC activity and finally enhances the endogenous opioid system via cyclic guanosine monophosphate production. We conclude that bLF may block the development of tolerance to morphine in mice, possibly via the selective activation of nNOS. | Zhang X, Rojas JC, Gonzalez-Lima F (2006) Methylene blue prevents neurodegeneration caused by rotenone in the retina. Neurotoxicity research 9, 47-57 [PubMed:16464752] [show Abstract] An experimental optic neuropathy model was used to test the hypothesis that methylene blue may protect the retinal ganglion cell layer from neurodegeneration caused by rotenone. Rotenone is a widely used pesticide that inhibits complex I, the first enzyme of the mitochondrial respiratory chain. Complex I dysfunction is linked to the degeneration of retinal ganglion cells in Leber's optic neuropathy. Methylene blue is a reduction-oxidation agent that can act as a powerful antioxidant and also as an enhancer of the electron transport chain, preventing formation of mitochondrial oxygen free radicals and promoting oxygen consumption. The neurodegeneration of the retina was studied in mice with intravitreal microinjection of rotenone alone, or in combination with increasing doses of methylene blue, in one eye, and the vehicle in the contralateral control eye. The effect of rotenone and rotenone plus methylene blue was investigated using two histological stains, complex I and Nissl, and two measurements, morphometric layer thickness and non-biased stereological cell counts. Rotenone induced neurodegeneration in the retinal ganglion cell layer 24 h after injection, as indicated by significant reductions in both the thickness and cell numbers of the retinal ganglion cell layer of eyes microinjected with rotenone as compared to the control eyes. This neurodegeneration was prevented in a dose dependent manner by the injection of methylene blue along with rotenone. It was concluded that rotenone-induced degeneration in the ganglion cell layer can be prevented by intravitreal injection of methylene blue. In vitro experiments showed that methylene blue is both a powerful antioxidant as well as an enhancer of cellular oxygen consumption and is able to reverse the oxidative stress and decrease in oxygen consumption induced by rotenone in brain homogenates. The findings suggest that methylene blue may be a promising neuroprotective agent in optic neuropathy and perhaps other neurodegenerative diseases caused by mitochondrial dysfunction. | Wang S, Boyjoo Y, Choueib A (2005) A comparative study of dye removal using fly ash treated by different methods. Chemosphere 60, 1401-1407 [PubMed:16054909] [show Abstract] The effect of different methods for fly ash treatment using conventional chemical, sonochemical and microwave method on dye adsorption in aqueous solution was investigated. Three basic dyes, methylene blue, crystal violet and rhodamine B, are employed for adsorption testing. It is found that fly ash shows different adsorption capacity depending on type of dyes. Chemical treatment using HCl will increase the adsorption capacity. The adsorption capacity of HCl treated fly ash varies with the preparation conditions. Microwave treatment is a fast and efficient method while producing the sample with the highest adsorption capacity. Solution pH and inorganic salts in dye solution can significantly influence the adsorption. The adsorption data have been analysed using Langmuir, Freundlich and Redlich-Peterson isotherms. The results indicate that the Freundlich and Redlich-Peterson models provide the better correlations with the experimental data. | Czímerová A, Jankovic L, Bujdák J (2004) Effect of the exchangeable cations on the spectral properties of methylene blue in clay dispersions. Journal of colloid and interface science 274, 126-132 [PubMed:15120287] [show Abstract] Adsorption of a cationic dye, methylene blue (MB), on the surface of montmorillonite leads to the molecular aggregation of dye cations, reflected by significant changes of dye optical properties. Montmorillonite samples, saturated with various inorganic cations (mono-, bi-, and trivalent, including those of transition metals), were used. Influence of the exchangeable cations on the MB aggregation was tested. Various properties of cations were considered (charge, diameter, acidity, hydration energies). Both direct and potential indirect effects of the cations were taken into account, such as salting-out effect, influence of the ions on solvent polarity, influence on swelling, colloid properties of montmorillonite dispersions, cation hydration properties, hydrolysis, and interaction of the cations with the clay surface. The spectra of MB in dispersions of montmorillonite saturated with NH4+, K+, Rb+, and Cs+ were significantly different from those of other reaction systems. Direct association between large monovalent cations and basal oxygen atoms of silicate probably leads to a partial fixation of the cations, which affects the ion exchange reaction and dye aggregation. Thus, the presence of large monovalent cations leads to the formation of fewer ordered H-aggregates in favor of monomers and aggregates of lower size. In these cases, dye species absorbing light of low energies also appeared in significant amounts and were assigned to J-aggregates, characterized by a head-to-tail intermolecular association. | Clifton J, Leikin JB (2003) Methylene blue. American journal of therapeutics 10, 289-291 [PubMed:12845393] [show Abstract] Methylene blue finds its major utilization in toxicology in the treatment of methemoglobinemia at a dose of 1 to 2 mg/kg intravenously. By interacting with methemoglobin and the erythrocyte's enzyme systems to reduce back to hemoglobin, methylene blue is a generally safe drug with dose-related hemolytic effects. People with G-6-PD deficiency, along with patients exposed to aniline dyes and dapsone, may present with special risks in the treatment of methemoglobinemia. | Leyh RG, Kofidis T, Kofidis T, Strüber M, Fischer S, Knobloch K, Wachsmann B, Hagl C, Simon AR, Haverich A (2003) Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass? The Journal of thoracic and cardiovascular surgery 125, 1426-1431 [PubMed:12830064] [show Abstract]
ObjectivesVasoplegia is a frequent complication after cardiopulmonary bypass that often requires the application of norepinephrine. In a number of cases, however, vasoplegia is refractory to norepinephrine. The guanylate cyclase inhibitor methylene blue could be an attractive treatment alternative in such cases. This study examines the results of methylene blue therapy for norepinephrine-refractory vasoplegia after cardiopulmonary bypass.MethodsA total of 54 patients with norepinephrine-refractory vasoplegia after cardiopulmonary bypass were treated with methylene blue (2 mg/kg) administered intravenously through a period of 20 minutes. The effects on hemodynamics, norepinephrine dosage, and clinical outcome were evaluated.ResultsThree patients (5.6%) died during the hospital stay. A clinically relevant increase in systemic vascular resistance and a decrease in norepinephrine dosage were observed in 51 patients within 1 hour after methylene blue infusion. Four patients (7.4%) had no response to methylene blue. No adverse effects related to methylene blue were observed.ConclusionsA single dose of methylene blue seems to be a potent approach to norepinephrine-refractory vasoplegia after cardiopulmonary bypass for most patients, with no obvious side effects. Guanylate cyclase inhibitors could be a novel class of agents for the treatment of norepinephrine-refractory vasoplegia after cardiopulmonary bypass. A controlled clinical trial is now needed to evaluate the role of methylene blue in this situation. | Martínez Portillo FJ, Fernández Arancibia MI, Bach S, Alken P, Jünemann KP (2002) [Methylene blue: an effective therapeutic alternative for priapism induced by intracavernous injection of vasoactive agents]. Archivos espanoles de urologia 55, 303-308 [PubMed:12068762] [show Abstract]
ObjectivePriapism is defined as prolonged and persistent erection of the penis without sexual stimulation. Etiologies of this condition are numerous. Recent advances in the understanding of erectile physiology have improved the prompt diagnosis and treatment of priapism. Treatment of priapism varies from a conservative medical to a drastic surgical approach. Normally, priapism is effectively treated with intracavernous vasoconstrictive agents or surgical shunting. Recent findings indicate methylene blue (MB), a guanylate cyclase inhibitor, to be a potential inhibitor of endothelial-mediated cavernous relaxation. This prompted us to assess the feasibility, the use and the effectiveness of MB in the treatment of priapism.Methods25 patients were treated for priapism. Etiologies were: 22 drug-mediated (PGE1 or papaverine/phentolamine mixture) after corpus cavernosum injection therapy (CCIT), 1 leukemia-induced and 2 idiopathic high-flow priapism. Patient ages ranged from 13 to 72 years. The average duration of priapism was 5 hours and 22 minutes after CCIT. MB was administered after blood aspiration of the corpora cavernosa. 5 ml of MB was injected intracavernously (i.c.) and left for 5 min. MB was then aspirated and the penis compressed for an additional 5 min.ResultsAll patients with CCIT-induced priapism were cured with MB alone. The 3 patients who did not respond to MB underwent i.c. phenylephrine administration and finally, if necessary, embolization of the pudendal artery. Etiology and duration of priapism were the strongest predictors for success with intracavernously administered MB. The primary side effects were a transient burning sensation and blue discoloration of the penis on injection of MB. The initial baseline erectile status was restored in all patients cured by MB.ConclusionsThese results confirm that MB is a safe and highly effective treatment agent for short-term pharmacologically-induced priapism. Furthermore, MB demonstrates distinct advantages over a-adrenergic agents for intracavernous use, such as lower costs, absence of systemic or local toxic side effects and shorter treatment time leading to faster detumescence. For this reason, MB is a suitable and safe substance for alternative routine intracavernous therapy in males with pharmacologically-induced priapism. | Evgenov OV, Sager G, Bjertnaes LJ (2001) Methylene blue reduces lung fluid filtration during the early phase of endotoxemia in awake sheep. Critical care medicine 29, 374-379 [PubMed:11246319] [show Abstract]
ObjectiveTo determine whether methylene blue (MB), an inhibitor of soluble guanylate cyclase and nitric oxide synthase, alters lung hemodynamics and fluid filtration after endotoxin in sheep.DesignProspective, randomized, controlled experimental study with repeated measurements.SettingUniversity animal laboratory.SubjectsEight yearling, awake sheep.InterventionsSheep were instrumented for a chronic study with vascular and lung lymph catheters. In two experiments, separated by 1 wk of recovery, the animals received intravenously either an injection of MB 10 mg/kg or a corresponding volume of 0.9% sodium chloride as pretreatment. Thirty minutes later, sheep received a bolus injection of Escherichia coli endotoxin 1 microg/kg, followed by either an infusion of MB 2.5 mg/kg/hr or a corresponding volume of 0.9% sodium chloride for 5 hrs.Measurements and main resultsMB decreased the early phase endotoxin-induced rises in pulmonary capillary pressure and pulmonary vascular resistance. MB also reduced the increments in lung lymph flow (QL) and protein clearance (CL) as well as the rightward shift of the permeability-surface area product (PS). In addition, MB diminished the decrease in cardiac output, stabilized mean arterial pressure, and precluded the rise in plasma and lung lymph cyclic guanosine 3'-5' monophosphate. However, during the late phase, MB-treated sheep presented with a faster rise in QL with no difference in CL and PS from the endotoxemic controls.ConclusionsDuring the early phase of endotoxemia in sheep, MB attenuates lung injury by decreasing the enhanced lung fluid filtration as a result of reduced pulmonary capillary pressure and permeability. However, MB does not counteract the late phase increase in lung fluid filtration. | Dutta K, Mukhopadhyay S, Bhattacharjee S, Chaudhuri B (2001) Chemical oxidation of methylene blue using a Fenton-like reaction. Journal of hazardous materials 84, 57-71 [PubMed:11376884] [show Abstract] Oxidation by Fenton-like reactions is proven and economically feasible process for destruction of a variety of hazardous pollutants in wastewater. We report herein the oxidation of methylene blue, a basic dye of thiazine series using a Fenton-like reaction at normal laboratory temperature and at atmospheric pressure. The effects of different parameters like the initial concentrations of dye, Fe2+, and H2O2, pH of the solution, reaction temperature, and added electrolytes on the oxidation of the dye present in dilute aqueous solution in the concentration range (3.13-9.39)x10(-5)mol dm(-3) (10-30 mg l(-1)) have been assessed. The results indicate that the dye can be most effectively oxidized in aqueous solution at dye:Fe(2+):H2O2 molar ratio of 1:1.15:14.1. More than 98% removal of the dye could be achieved in 1h in the pH range 2.2-2.6 at 299 K which corresponds to about 81% reduction of the initial COD. The results will be useful for designing the treatment systems of various dye-containing wastewaters. | Peer G, Itzhakov E, Wollman Y, Chernihovsky T, Grosskopf I, Segev D, Silverberg D, Blum M, Schwartz D, Iaina A (2001) Methylene blue, a nitric oxide inhibitor, prevents haemodialysis hypotension. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 16, 1436-1441 [PubMed:11427637] [show Abstract]
BackgroundPlasma nitric oxide (NO) levels have been found to be high in haemodialysis (HD) patients, especially in those prone to hypotension in dialysis. The aim of the study was to prevent dialysis hypotension episodes by i.v. administration of methylene blue (MB), an inhibitor of NO activity and/or production.MethodsMB was given i.v. in 18 stable HD patients with hypotensive episodes during almost every dialysis, in 18 HD patients without hypotension during dialyses, and in five healthy controls. MB was given as a bolus of 1 mg/kg bodyweight followed by a constant infusion of 0.1 mg/kg bodyweight lasting 210 min until the end of the dialysis session and only as a bolus on a non-dialysis day. Systolic and diastolic blood pressures (BP) were measured at 10-min intervals during HD sessions with or without MB and on a non-dialysis day with MB.ResultsIn hypotension-prone patients, MB completely prevented the hypotension during dialysis and increased both systolic and diastolic BP on non-dialysis days. In normotensive patients, MB increased BP during the first hour of dialysis and for 90 min on the non-dialysis day. The BP in the healthy controls remained unchanged. Plasma and platelet NO(2)+NO(3) (stable metabolites of NO) levels were determined. The NO(2)+NO(3) generation rate in the first post-dialysis day was calculated. The plasma and platelet NO(2)+NO(3) were higher in the hypotensive group than in the normotensive dialysis group. The generation rate of nitrates was higher (P<0.01) in the hypotensive group (1.21+/-0.13 micromol/min and 0.74+/-0.16 after MB) than in the normotensive patients (0.61+/-0.11 micromol/ min and 0.27+/-0.14 after MB). No side-effects were recorded.ConclusionsMB is an efficient therapy in the prevention of dialysis hypotension. | Segawa K, Minami K, Shiga Y, Shiraishi M, Sata T, Nakashima Y, Shigematsu A (2001) Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway. Nephron 87, 263-268 [PubMed:11287762] [show Abstract] We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K(ATP)) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 microM to 1 mM inhibited [(3)H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 microM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K(ATP) mediators. Cromakalim, a K(ATP) activator, and glibenclamide, a K(ATP) inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway. | Cohen N, Robinson D, Ben-Ezzer J, Hemo Y, Hasharoni A, Wolmann Y, Otremski I, Nevo Z (2000) Reduced NO accumulation in arthrotic cartilage by exposure to methylene blue. Acta orthopaedica Scandinavica 71, 630-636 [PubMed:11145393] [show Abstract] Nitric oxide (NO) appears to be a final common inflammation mediator of cartilage degradation. Halting the pathological formation of excessive NO, by suppressing the inducible NO synthase (iNOS) activity, may help to preserve cartilage integrity. We used fresh ex-vivo human articular cartilage explants from normal and arthrotic joints for assessment of NO levels, as determined by its nitrite degradation products and nitric oxide synthase expression. We measured matrix proteoglycan content, assessed by image analysis of alcian blue staining, and proteoglycan synthesis, assessed by sulfate incorporation into proteoglycans. The effect of methylene blue, a nitric oxide synthase inhibitor, on matrix preservation was evaluated. Cartilage discs in vitro, derived from normal appearing joints, secreted about one tenth as much NO compared to discs derived from arthrotic cartilage. Cartilage explants showed a time-dependent reduction in the amount of aggrecan within the cartilaginous matrix. Addition of methylene blue to the growth medium lowered nitric oxide accumulation and prevented matrix degradation in the cultured cartilage discs. The cartilage matrix preservation effect was mediated through downregulation of all three isoforms of NOS, i.e., the neuronal NOS, endothelial NOS and inducible NOS and upregulation of TGF beta receptor in the chondrocytes. Our findings indicate that inhibition of NOS activity preserves cartilage matrix in vitro. | BROOKS MM (1948) Methylene blue, an antidote to altitude sickness. The Journal of aviation medicine 19, 298 [PubMed:18873190] |
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