N-methyl Glucamine Research Articles

Treatment of Refractory Mucosal Leishmaniasis Is Associated with Parasite Overexpression of HSP70 and ATPase and Reduced Host Hydrogen Peroxide Production (Brief Report).

Mucosal leishmaniasis (ML) is a deforming type of American Tegumentary Leishmaniasis caused by Leishmania (Viannia) braziliensis that frequently does not respond to treatment. Despite its relapsing clinical course, few parasites are usually found in mucosal lesions. Host and parasite factors may be responsible for this paradox in the pathogenesis of the disease, allowing for both a low parasite burden and the inability of the host to clear and eliminate the disease. In this work, we present a clinical case of relapsing ML that was treated for 25 years without success with SbV, N-methyl glucamine, sodium stibogluconate, amphotericin B deoxycholate, gabromycin, antimonial plus thalidomide, liposomal amphotericin B, Leishvacin (a vaccine made in Brazil) and miltefosine. In a comparative analysis using nanoscale liquid chromatography coupled with tandem mass spectrometry of protein extracts of L. (V.) braziliensis promastigotes isolated from the patient and from the reference strain (MHOM/BR/94/M15176), we observed increases in ATPase and HSP70 protein levels in the parasite. We also observed an impairment in the production of hydrogen peroxide by peripheral mononuclear blood monocytes (PBMCs), as assessed by the horseradish peroxidase-dependent oxidation of phenol red. We hypothesise that these parasite molecules may be linked to the impairment of host parasiticidal responses, resulting in Leishmania persistence in ML patients.

Structure design and performance optimization of PVDF-CTFE nanofibrous composite nanofiltration membrane modified by C–Cl active site grafting

The substrate membrane plays a crucial role in determining the performance of composite nanofiltration membranes prepared by interfacial polymerization (IP). In this study, persistent hydrophilic modification of polyvinylidene fluoride-co-chlorotrifluoroethylene (PVDF-CTFE) was achieved by incorporating N-methylglucamine (N-MG) without altering the membrane's morphology or pore size. Moreover, thin-film nanofibrous composite (TFNC) nanofiltration membranes were prepared using the surfactant assembly regulated interfacial polymerization (SARIP) method with the modified PVDF-CTFE@N-MG nanofibrous membrane as the substrate. The effect of N-MG addition on the substrate membrane's hydrophilicity and the structure and performance of the polyamide (PA) separation layer was investigated. The results showed that the addition of N-MG significantly improved the hydrophilicity of the PVDF-CTFE nanofibrous membrane. The TFNC-5 membrane, prepared with the modified PVDF-CTFE@N-MG nanofibrous membrane as the substrate, exhibited permeability exceeding 13.5 L m−2 h−1·bar−1 for various dye solutions at 3 bar pressure, with rejection rates above 98 %. It also demonstrated excellent selective separation performance (separation factor for NaCl/Orange G reaching 97.38) and long-term operational stability. This work provides a method for the preparation of low-pressure, high-flux nanofiltration membranes, which is applicable to seawater desalination and dye wastewater treatment.

Preparation of N-MG-modified PVDF-CTFE substrate composite nanofiltration membrane and its selective separation of salt and dye.

Poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) is considered an ideal membrane material for the treatment of complex environmental water due to its exceptional thermal stability and chemical resistance. Thus, to expand its application in the field of nanofiltration (NF) membranes, in this study, N-methylglucamine (N-MG) was used to hydrophilically modify PVDF-CTFE, overcoming the inherent hydrophobicity of PVDF-CTFE as a porous substrate membrane, which leads to difficulties in controlling the interfacial polymerization (IP) reaction and instability of the separation layer structure. The -OH present in N-MG could replace the C-Cl bond in the CTFE chain segment, thus enabling the hydrophilic graft modification of PVDF-CTFE. The influence of the addition of N-MG on the surface and pore structure, wettability, permeability, ultrafiltration separation, and mechanical properties of the PVDF-CTFE substrate membrane was studied. According to the comparison of the comprehensive capabilities of the prepared porous membranes, the M4 membrane with the addition of 1.5 wt% N-MG exhibited the best hydrophilicity and permeability, indicating that it is a desirable modified membrane for use as an NF substrate membrane. The experiments showed that the rejection of Na2SO4 by the NF membrane was 96.5% and greater than 94.0% for various dyes. In the test using dye/salt mixed solution, this membrane exhibited a good separation selectivity (CR/NaCl = 177.8) and long-term operational stability.

N-methylglucamine modified poly (vinyl chloride) support assists the construction of uniform dually charged nanofiltration membrane via interfacial polymerization

Support membrane plays a crucial role in interfacial polymerization (IP) reaction for nanofiltration membranes (NFMs) preparation and dramatically affects the properties of NFMs. This paper reported NFMs with improved uniformity and dually charged separation layer, formed on properly modified poly(vinyl chloride) (PVC) substrate by N-methylglucamine (NMG) molecules. The effect of NMG grafting on the structure and performance of PVC UF membranes and NFMs was studied. The results showed that the appropriate grafting of NMG molecules on the surface of PVC UF membrane significantly improved the hydrophilicity of PVC UF membrane without affecting the pore size. It assisted the convenient formation of uniform and defect-free dually charged polyamide separation layer by regulating the adsorption, storage and dispersion of diamine monomers. Simultaneous high rejection for both divalent anions and cations was obtained. This work provides a convenient and effective strategy to construct uniform dually charged NFMs.

New boron selective sorbents for sorption – membrane hybrid system

The synthesis and properties of core-shell sorbents dedicated to the removal of borates from aqueous solutions were described. By modification of polymer matrices with vinylbenzyl chloride followed by its derivatization with N-methyl glucamine a new kind of sorbents were obtained. The testing of boron sorption reviled that the process efficiency was related to the pore diameter and the content of ligand in the sorbent. The best material for use in a hybrid system, where boron is absorbed by fine particles and removed in microfiltration, was Poropak Q with a specific surface area of 300 m2/g.

Enhanced adsorption-photocatalytic reduction removal for Cr (VI) based on functionalized TiO2 with hydrophilic monomers by pre-radiation induced grafting-ring opening method

A novel and enhanced adsorption-photocatalytic reduction performances of Cr (VI) photocatalyst on TiO2-g-GMA/NMG (noted as: TGN) was prepared by pre-radiation grafting and ring-opening reaction with Glycidyl methacrylate (GMA) and N-methyl glucamine (NMG). The surface and microstructure properties of photocatalyst were manifested by FTIR, TG, XRD, DRS, XPS, BET and contact angle. Morphologies of TGN were characterized further by FE-SEM and HR-TEM. The highly activity of TGN was tested by the reduction of Cr (VI) into Cr (III) in aqueous medium under mixed light. The results showed that the TGN (NMG:18%, 60 kGy) also had a highest removal rate (81.8%) of Cr (VI) only for 1 h at [Cr(VI)] = 10 ppm, [TGN] = 10 mg/50 mL and pH = 3.0. In addition, the adsorption-photocatalytic reduction mechanism of Cr (VI) by TGN consisted of three processes was proposed. Generally, this TGN complex photocatalyst has good potential for application in the field of water pollution treatment containing high valence heavy metal ions.

Facile Fabrication of N-Methyl-D-Glucamine Grafted HDPE Particle as Adsorbent for Boron Removal from Aqueous Solution

Glycidyl methacrylate (GMA) was grafted onto the surface of HDPE particles by radiation grafting and emulsion graft copolymerization. And subsequent ring-opening reaction of expoxy groups in poly-GMA graft chains with N-methylglucamine (NMG) was conducted to synthesis the boron adsorbent. The synthesis condition (radiation dose and NMG concentration) was optimized and characterized by IR and SEM. Adsorption behaviors of the boron adsorbent for boron removal presented that adsorption kinetics was well described by pseudo-second-order kinetic mode. The adsorption isothermal was well fitted with both Langmuir and Freundlich isotherm models. The adsorption capacity for boron reached 15.63 mg/g at optimal pH 8. Dynamic experiment revealed that boron could be efficiently adsorbed by the boron adsorbent and fully desorbed using 13 BV of 1 mol/L HCl.

Study of the efficacy of N-methyl glucamine antimoniate (SbV) associated with photodynamic therapy using liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL6 mice.

Pentavalent antimonials remain first-line drugs in the treatment of cutaneous leishmaniasis (CL); however, adverse effects and drug resistance have led to the search for less toxic and more effective treatments. As an alternative, topical phthalocyanine has been studied and its efficacy and low toxicity demonstrated. We aimed to study the in vivo efficacy of N-methyl glucamine antimoniate (NMG) associated with photodynamic therapy (PDT) with topical liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of experimental CL by L. amazonensis. Experimental study with 54 C57BL6 isogenic mice divided into 9 groups including uninfected control, untreated control, PDT with AlClPC + NMG at doses of 10 and 20 mgSbV/Kg/day. The criteria to evaluate the treatment efficacy were: paw diameter, amastigote count, culture, viability test and parasite counts using MTT (3-bromo-4,5-dimethylthiazol-2,5-diphenyl-tetrazolium bromide). Treatment of CL with the association of NMG20 + PDT with AlClPC showed significant reduction of paw diameter, amastigote count, cultures, viability test and parasite counts. Parasite reduction occurred at the 10th and 20th days of treatment and 60 days after treatment ended, indicating that parasites did not multiply again. The NMG10 + PDT group with AlClPC presented results equivalent to gold-standard treatment (20 mgSbV/kg/day). Biochemical and histopathological evaluation showed minor changes. Treatment of CL caused by L. amazonensis with NMG20 mgSbV/kg/day + PDT with AlClPC was more effective than the traditional NMG20 mgSbV/kg/day.

American tegumentary leishmaniasis in Brazil: a critical review of the current therapeutic approach with systemic meglumine antimoniate and short-term possibilities for an alternative treatment.

Meglumine antimoniate (MA; Glucantime®), the 80-year-old first-line systemic treatment for all forms of American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) amazonensis, is highly toxic, presents adverse side-effects and may not attain clinical and parasitological cure. This critical review examines the necessity for intramuscular/intravenous administration of MA, the alternatives to this approach, and the possibilities of developing affordable, accessible and non-toxic drugs or new delivery methods. PubMed searches were performed using the terms 'cutaneous leishmaniasis' or 'American tegumentary leishmaniasis' in combination with 'meglumine antimoniate' or 'N-methyl glucamine' or 'drug repositioning' or 'nanotechnology'. Searches covered a period of 20years of peer reviewed journals and technical bulletins. We explored the mode of action, pharmacokinetics, toxicity and efficacy of MA, evaluated the progress of ATL therapy in Brazil, and examined the potential of drug repositioning and nanotechnology in accelerating the introduction and/or optimisation of an alternative treatment. The evidence suggests that ATL therapy will continue to rely on systemic MA in the foreseeable future even though an intralesional subcutaneous route has evolved over the last 10years. The chances of developing a novel drug for ATL or a new mode of delivery of MA are low. While MA nanocarriers afford a promising approach, this technology is still in its infancy. A more immediate solution would be the production of a bioequivalent of miltefosine, an efficacious oral agent no longer protected by patent. Development of a contemporary treatment requires governmental commitment in bringing together private and public sectors.

Lesions of Cutaneous Leishmaniasis Elicited after Local Trauma: A Case Report

In Brazil there is an average of 30,000 cases of Cutaneous Leishmaniasis reported annually, and around the world it happens for about each 20 seconds. Although there are still opportunities to contribute with studies about this disease; supporting the medical community, especially dermatologists, mainly because of the necessity of knowing that a relatively simple procedure can result such a relevant trauma. Female patients presented erythematous plaque in the limb. Lesion appeared days after laser sessions for hair removal. Biopsy showed amastigotes forms and positive culture. After unsuccessful treatment it was managed with N-methyl glucamine 20 mgSbV/kg/day, during 20 days, there was significant improvement of the clinical picture. This study aims to present a case report of Cutaneous Leishmaniasis initiated after local trauma. Literature reports describe primary or secondary lesions of Cutaneous Leishmaniasis elicited after a local trauma. The mechanism used in order to explain these events was the migration of infected macrophages induced by cytokines. Similar events have also been reported as part of the locus minoris resistentiae concept that comprises situations in which microorganisms have a tendency to settle at places of weakened resistance. Considering that Leishmaniasis lesions are usually developed in promastigote forms are inoculated by the Phlebotominae, in this case it was noted that the infection has been favored by the local trauma.

Epidemiology of Cutaneous Leishmaniasis in a Colombian Municipality.

This study describes the epidemiological and clinical characteristics of leishmaniasis and the pharmacological treatment of this disease in the municipality of Pueblo Rico, Risaralda, between January 2010 and December 2014. An observational study was conducted using information from the clinical records and epidemiological reports of patients diagnosed and confirmed with leishmaniasis of any age and sex, including sociodemographic, clinical, and pharmacological variables of the therapy received. Univariate and bivariate analyses were performed. A total of 539 cases of leishmaniasis were confirmed, with 29.5% occurring in children under 5 years of age. The median age was 10 years, with predominance in males (55.5%). The indigenous Emberá (aboriginal Americans) were the most affected (50.8%), and 93.3% of cases occurred in people living in scattered rural areas. All lesions corresponded to cutaneous leishmaniasis, of which 251 patients had compromise of the upper limbs (46.6%), 221 of the face (41.0%), and 139 of the lower limbs (25.8%). Pentavalent antimony salts (n-methyl glucamine and sodium stibogluconate) were prescribed in 77.6% (N = 418) of the cases; miltefosine was the second most frequently prescribed medication (21.5%, N = 116). The inhabitants of rural areas and the indigenous communities are at a higher risk of acquiring the infection, particularly among infants, which highlights the importance of the biological, social, and demographic factors involved in the disease. There is a need to seek effective public health actions and further research this disease.

The direct costs of treating human visceral leishmaniasis in Brazil.

The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

Topical Treatment of Cutaneous Leishmaniasis: Wound Reduction in Mice Using N-Methyl Glucamine from PVP and Nano Clay Membranes

Topical Treatment of Cutaneous Leishmaniasis: Wound Reduction in Mice Using N-Methyl Glucamine from PVP and Nano Clay Membranes

Cutaneous Leishmaniasis Following Local Trauma: A Case Report

In Brazil there is an average of 30,000 cases of Cutaneous Leishmaniasis reported annually, and around the world it happens for about each 20 seconds. Although there are still opportunities to contribute with studies about this disease; supporting the medical community, especially dermatologists, mainly because of the necessity of knowing that a relatively simple procedure can result such a relevant trauma. Female patients presented erythematous plaque in the limb. Lesion appeared days after laser sessions for hair removal. Biopsy showed amastigotes forms and positive culture. After unsuccessful treatment it was managed with N-methyl glucamine 20 mgSbV/kg/day, during 20 days, there was significant improvement of the clinical picture. This study aims to present a case report of Cutaneous Leishmaniasis initiated after local trauma. Literature reports describe primary or secondary lesions of Cutaneous Leishmaniasis elicited after a local trauma. The mechanism used in order to explain these events was the migration of infected macrophages induced by cytokines. Similar events have also been reported as part of the locus minoris resistentiae concept that comprises situations in which microorganisms have a tendency to settle at places of weakened resistance. Considering that Leishmaniasis lesions are usually developed in promastigote forms are inoculated by the Phlebotominae, in this case it was noted that the infection has been favored by the local trauma.

Environmentally evaluated HPLC-ELSD method to monitor enzymatic synthesis of a non-ionic surfactant.

BackgroundN-Lauroyl-N-methylglucamide is a biodegradable surfactant derived from renewable resources. In an earlier study, we presented an enzymatic solvent-free method for synthesis of this compound. In the present report, the HPLC method developed to follow the reaction between lauric acid/methyl laurate and N-methyl glucamine (MEG) and its environmental assessment are described.ResultsUse of ultraviolet (UV) absorption or refractive index (RI) detectors did not allow the detection of N-methyl glucamine (MEG). With Evaporative light scattering detector ELSD, it was possible to apply a gradient elution, and detect MEG with a limit of detection, LOD = 0.12 μg. A good separation of the peaks: MEG, lauric acid, product (amide) and by-product (amide-ester) was achieved with the gradient program with a run time of 40 min. The setting of ELSD detector was optimized using methyl laurate as the analyte. LC-MS/MS was used to confirm the amide and amide-ester peaks. We evaluated the greenness of the developed method using the freely available software HPLC-Environmental Assessment Tool (HPLC-EAT) and the method got a scoring of 73 HPLC-EAT units, implying that the analytical procedure was more environmentally benign compared to some other methods reported in literature whose HPLC-EAT values scored up to 182.ConclusionUse of ELSD detector allowed the detection and quantification of the substrates and the reaction products of enzymatic synthesis of the surfactant, N-lauroyl-N-methylglucamide. The developed HPLC method has acceptable environmental profile based on HPLC-EAT evaluation.

Speciation of antimony in injectable drugs used for leishmaniasis treatment (Glucantime®) by HPLC-ICP-MS and DPP

Meglumine antimonate is the active of Glucantime® used for the treatment of leishmaniasis, a tropical disease caused by parasitic protozoa, and it is estimated that 12 million people worldwide are affected. This drug mainly contains Sb(V) under the form of an organic complex with N-methylglucamine (NMG). During the synthesis of this molecule, traces of Sb(III) may be present, also probably complexed. Due to the fact that Sb(III) is considered more toxic than Sb(V), it is important to evaluate the Sb(III) concentration in the drug samples. In the literature, very different concentrations for residual concentrations of Sb(III) in the drug ampoules are found. Therefore, to have a true insight of antimony speciation, two independent analytical methods were developed in this work. We used an anion exchange method coupled with inductively coupled plasma mass spectrometry (ICP-MS) which was cross-referenced with an electrochemistry method (differential pulse polarography (DPP)) that could be used for routine analysis on the production site. To obtain Sb species in detectable forms, the complexes between Sb species and NMG need to be broken. This was obtained by diluting samples in hydrochloric acid in deaerated conditions to avoid Sb redox reactions. For the two analytical methods, the HCl concentration was optimized to obtain simultaneously a complete destruction of the complexes as well as limited redox reactions for Sb(V) and Sb(III) released species. For high-performance liquid chromatography (HPLC)-ICP-MS, a dilution with 5 M HCl gives the better results. The side reaction is an oxidation of Sb(III) which can be limited by the removal of oxygen. When DPP is used, the major problem is the reduction of Sb(V) which is present in high amount in the samples. Working with 0.6 M HCl allows this problem to be minimized. When applied to different lots of Glucantime®, Sb(III) concentration values are in good agreement for the two analytical methods, with, for HPLC-ICP-MS, the advantage of the simultaneous detection of both Sb redox species.

THE OPTIMIZATION OF ENZYMATIC SYNTHESIS FOR LAUROYL-N-METHYL GLUCAMIDE SURFACTANTS

The optimization of enzymatic synthesis for lauroyl-N-methyl glucamide surfactants is studied. The fraction of palm kernel oil namely lauric acid (AL) was amidificationed with N-methyl glucamine (MGL) to produce lauroyl-N-methyl glucamide. Study was carried out by using immobilized lipase from Candida antarctica (Novozyme 435®), and tert-amylalcohol as a solvent. Response Surface Methodology (RSM) based on a five level, three variable design was employed, firstly, for studying the interactive effect of various parameters on the reaction, and secondly, for the optimization. The reaction parameters observed were Novozyme concentration, substrate molar ratio, and temperature. Simultaneously increasing Novozyme concentration, substrate molar ratio, and temperature improves the reaction yield and the effect of temperature is noted more significant. The expected optimum condition was at molar ratio MGL:AL 1:1, the Novozyme concentration of 8% and the reaction temperature of 50-55 °C. The reactions at the optimum condition produce the convertion of lauric acid of 64.5% and yield of 96.5%. With the optimization procedure the higher alkyl glucamide yield was achieved.

A pilot study comparing low‐dose liposomal amphotericin B with N‐methyl glucamine for the treatment of American cutaneous leishmaniasis

Cutaneous leishmaniasis is an infectious re-emerging disease that has increased in incidence worldwide. Antimony, a highly toxic drug, remains the first choice therapy to treat it. Liposomal amphotericin B is active against Leishmania and is less toxic than antimony. To compare low-dose liposomal amphotericin B with N-methyl glucamine for the treatment of American cutaneous leishmaniasis. In a controlled open-label trial 35 patients with a localized form of American cutaneous leishmaniasis were included. They were allocated to a first group treated with 1.5 mg/kg/day of liposomal amphotericin B for 5 days, or to a second one treated with 20 mgSbV/kg/day of N-methyl glucamine for 20 days. In the first group, 50% and 81% of patients experienced a clinical cure and clinical improvement respectively. There was a 100% clinical cure in the second group. Liposomal amphotericin B seems to be promising and safe for the treatment of American cutaneous leishmaniasis.

Acylation of sugar amides over Algerian bentonite and mcm-41 materials

The condensation of sugar with fatty acids in an organic media is possible by chemical amidification without fastidious steps by hydroxyl group protection/deprotection. The acylation of sugar (N-methyl glucamine) with fatty acids (lauric acid, palmitic acid and stearic acid) is catalyzed in the presence of two inorganic and acid solid catalysts: Algerian clay called bentonite of Maghnia and mesoporous material of type (Al–MCM-41). The results obtained with this last solid (i.e. MCM-41) are very encouraging.

Absence of direct effects on the dopamine D2 receptor by mGluR2/3‐selective receptor agonists LY 354,740 and LY 379,268

We previously reported the absence of high-affinity binding of the group II metabotropic glutamate receptor agonists LY 354,740 and LY 379,268 to the D2L dopamine receptor. A rebuttal to our findings has since been reported (see Introduction section); this study represents our response. Analysis by LCMS of LY 354,740 and LY 379,268 used in this study revealed the correct molecular mass for these compounds. Both LY 354,740 and LY 379,268 exhibited potent agonist activity for mGluR₂ in the ³⁵S-GTPγS assay. Functionally, neither compound displayed antagonist activity in the GTPγS assay with recombinant D₂. At concentrations up to 10 μM, both compounds failed to displace [³H]-raclopride, [³H]-PHNO, or [³H]-domperidone in filter-binding assays under isotonic (120 mM NaCl or N-methyl glucamine) or low-ionic strength (no NaCl or N-methyl glucamine) conditions. Some displacement of [³H]-domperidone (20-40%) was observed at 30 μM of LY 354,740 under low-ionic strength and under isotonic conditions in the absence of NaCl. No displacement of [³H]-domperidone was detected in a two site model at lower (<100 nM) concentrations of either compound. Moreover, no D₂ activity was observed for LY 354,740 or LY 379,268 in the CellKey™ (cellular dielectric spectroscopy) assay. In this communication, we discuss the possible reasons for differences in our study and the previously published work and implications of these studies for mechanisms of antipsychotic action.