Coenzyme M Research Articles

Ethylene and epoxyethane metabolism in methanotrophic bacteria: comparative genomics and physiological studies using Methylohalobius crimeensis.

The genome of the methanotrophic bacterium Methylohalobius crimeensis strain 10Ki contains a gene cluster that encodes a putative coenzyme-M (CoM)-dependent pathway for oxidation of epoxyethane, based on homology to genes in bacteria that grow on ethylene and propylene as sole substrates. An alkene monooxygenase was not detected in the M. crimeensis genome, so epoxyethane is likely produced from co-oxidation of ethylene by the methane monooxygenase enzyme. Similar gene clusters were detected in about 10% of available genomes from aerobic methanotrophic bacteria, primarily strains grown from rice paddies and other wetlands. The sparse occurrence of the gene cluster across distant phylogenetic groups suggests that multiple lateral gene transfer events have occurred in methanotrophs. In support of this, the gene cluster in M. crimeensis was detected within a large genomic island predicted using multiple methods. Growth studies, reverse transcription-quantitative PCR (RT-qPCR) and proteomics were performed to examine the expression of these genes in M. crimeensis. Growth and methane oxidation activity were completely inhibited by the addition of >0.5% (v/v) ethylene to the headspace of cultures, but at 0.125% and below, the inhibition was only partial, and ethylene was gradually oxidized. The etnE gene encoding epoxyalkane:CoM transferase was strongly upregulated in ethylene-exposed cells based on RT-qPCR. Proteomics analysis confirmed that EtnE and nine other proteins encoded in the same gene cluster became much more predominant after cells were exposed to ethylene. The results suggest that ethylene is strongly inhibitory to M. crimeensis, but the bacterium responds to ethylene exposure by expressing an epoxide oxidation system similar to that used by bacteria that grow on alkenes. In the obligate methanotroph M. crimeensis, this system does not facilitate growth on ethylene but likely alleviates toxicity of epoxyethane formed through ethylene co-oxidation by particulate methane monooxygenase. The presence of predicted epoxide detoxification systems in several other wetland methanotrophs suggests that co-oxidation of ambient ethylene presents a stress for methanotrophic bacteria in these environments and that epoxyethane removal has adaptive value.

Exploration of adsorption properties of organic corrosion inhibitors on layered double hydroxide nanosheet: A molecular dynamics simulation study

Understanding the adsorption of organic corrosion inhibitors with different functional groups on layered double hydroxide (LDH) nanosheet is crucial for the synthesis of these protective materials. In this study, the adsorption process of five deprotonated organic corrosion inhibitors—lactate (Lc), 2-hydroxybenzothiazole (2-OH-BTH), 2-mercaptoethanesulfonic acid (MS), N,N-dimethylethanolamine (DMEA), and eugenol (EG)—on LDH nanosheets was simulated. The adsorption rate, adsorption configuration, and adsorption stability between LDH nanosheet and organic corrosion inhibitors were investigated throughout the entire adsorption process. The study observed consistency in the adsorption rate and stability of these organic corrosion inhibitors in the following order: Lc > 2-OH-BTH > MS > DMEA > EG. Additionally, hydrogen bonds between the organic corrosion inhibitors and the LDH nanosheet is the primary mechanism driving adsorption. The number and stability of hydrogen bonds influenced both the adsorption rate and stability. It is noteworthy that 2-OH-BTH and DMEA have not previously been incorporated into LDH. There is potential for these two organic corrosion inhibitors to be modified for LDH, suggesting significant prospects for future research.

2-Mercaptoethanesulfonic Acid as an Effective Free-Radical Scavenger in Perfluorosulfonic Acid Membrane-Based Polymer Electrolyte Membrane Fuel Cells

Ceria nanoparticle-based free-radical scavengers for the mitigation of oxidative damage in perfluorosulfonic acid (PFSA)-based polymer electrolyte membrane fuel cells (PEMFCs) suffer from the drawbacks of lowered protonic conductivity and leaching in the acidic environment of a PEMFC. As an alternative to ceria, here we demonstrate that oxidative damage can be mitigated by functionalization of Nafion with 2-Mercaptoethanesulfonic acid (MESA) in different (0.1–1.0 wt%) ratio. The spectroscopic investigation indicated successful functionalization of MESA over the Nafion chain and resulting Nafion-MESA composite membranes displayed improved hydration and swelling behavior, and thermal and mechanical properties. At ≤60 °C (95% relative humidity), the protonic conductivity of composite membranes was higher than/equivalent to that of pristine Nafion membrane; however, at ≥70 °C it was ∼6%–8% lower. At 80 °C, conductivity of Nafion-MESA-0.1 wt%, Nafion-MESA-0.25 wt%, pristine Nafion, and state-of-the-art Nafion-CeO2−1wt% membranes were 1.72 × 10−1, 1.67 × 10−1, 1.8 × 10−1, and 1.6 × 10−1 S∙cm−1, respectively. The fluoride emission rate value for the same membranes were 0.30, 0.17, 1.39, and 0.27 mg∙g−1, respectively, thus indicating that Nafion-MESA membranes can substitute the ceria-based membranes as a chemically stable membrane electrolyte in PEMFCs.

Use of mesna prophylaxis in patients with cyclophosphamide-treated ANCA-associated vasculitis: cross-sectional survey of practitioners.

There may be some diversity in the practice of co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV). To assess the practice of prescribing mesna prophylaxis for CYC-treated patients with AAV. We invited authors of publications on AAV referenced in MEDLINE over the previous 10 years to participate in an anonymous online survey. Respondents were eligible if they were involved in CYC treatments for AAV. The survey asked about the characteristics of the respondents and their practice in using CYC and mesna to treat AAV and the underlying rationale. We compared 18 variables between mesna prescribers and their counterparts to identify factors associated with mesna use. In total, 139 eligible individuals completed the survey. The participants were from 34 countries and were essentially physicians (98%). Overall, 68%, 19% and 13% of respondents prescribed mesna systematically, never, or on a selective basis. As compared with never/selective-prescribers, systematic-prescribers were more often ≤ 39 years old (P = 0.008), more often used intermittent pulse therapy as the exclusive/predominant CYC administration scheme (P < 0.001), were more frequently based in France/Germany/Italy than in England/United States (P < 0.001), and more often indicated adherence to local standards (P = 0.003) or (inter)national guidelines for AAV (P < 0.001) as a rationale for their mesna practice. Never/selective-prescribers more commonly reported that their mesna prescription pattern had changed as compared with their former practice (P < 0.001). Systematic co-prescription of mesna is the prevailing practice for CYC treatments for AAV. The practice seems to involve practicability considerations and differs between generations.

Cysteinylprolyl ester-mediated drug release from a lipid–drug conjugate

For small-molecule drugs, lipidation via a cleavable linkage can extend half-life in circulation through interaction with albumin. Here we modified the cysteinylprolyl ester (CPE) system used in peptide thioester synthesis, which normally requires basic conditions, for use as an self-immolative linker and release device for a lipid-gemcitabine conjugate. To improve release under physiological conditions for medical application, a methyl group at the α-position of cysteine on the CPE unit was incorporated in anticipation of the Thorpe-Ingold effect. As a result, Ac-Gly-(α-Me)Cys(SH)-Pro-gemcitabine 11 drastically promoted the release of gemcitabine in comparison with Ac-Gly-Cys(SH)-Pro-gemcitabine 10. Furthermore, in the presence of bovine serum albumin and/or 2-mercaptoethanesulfonic acid, the gentle and continuous release of gemcitabine from the lipid–gemcitabine conjugate 16 was achieved. In addition to gemcitabine, this method could allow high clearance drugs, including nucleic acid and prostacyclin derivatives, to maintain their biological activity long enough to become effective.

Mucoadhesive polymers: Design of S-protected thiolated cyclodextrin-based hydrogels

AimThis study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies on porcine small intestinal mucosa and on porcine buccal mucosa. MethodsFree thiol groups of heptakis(6-deoxy-6-thio)-β-cyclodextrin (β-CD-SH) were S-protected with 2-mercaptoethanesulfonic acid (MESNA) followed by crosslinking with citric acid. Cytotoxicity was assessed by hemolysis as well as resazurin assay. Hydrogels were characterized by their rheological and mucoadhesive properties. Ritonavir was employed as model drug for in vitro release studies from these hydrogels. ResultsThe structure of S-protected β-CD-SH was confirmed by IR and 1H NMR spectroscopy. Degree of thiolation was 390 ± 7 µmol/g. Hydrogels based on native β-CD showed hemolysis of 12.5 ± 2.5 % and 13.6 ± 2.7 % within 1 and 3 h, whereas hemolysis of just 3.5 ± 2.8 % and 3.9 ± 3.0 % was observed for the S-protected thiolated CD hydrogels, respectively. Both native and S-protected thiolated hydrogels showed minor cytotoxicity on Caco-2 cells. Rheological investigations of S-protected thiolated β-CD-based hydrogel (16.2 % m/v) showed an up to 13-fold increase in viscosity in contrast to the corresponding native β-CD-based hydrogel. Mucosal residence time studies showed that thiolated β-CD-based hydrogel is removed to a 16.6- and 2.4-fold lower extent from porcine small intestinal mucosa and porcine buccal mucosa in comparision to the native β-CD-based hydrogel, respectively. Furthermore, a sustained release of ritonavir from S-protected thiolated β-CD-based hydrogels was observed. ConclusionBecause of their comparatively high mucoadhesive and release-controlling properties, S-protected thiolated β-CD-based hydrogels might be promising systems for mucosal drug delivery.

Superfluorinated, Highly Water-Soluble Polyphosphazenes as Potential 19F Magnetic Resonance Imaging (MRI) Contrast Agents.

"Hot spot" 19F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, 19F-MRI's direct detection has a unique advantage in vivo, as the human body exhibits a negligible background 19F-signal. However, existing perfluorocarbon (PFC) or PFC-based contrast materials suffer from several limitations, including low longitudinal relaxation rates and relatively low imaging efficiency. Hence, we designed a macromolecular contrast agent featuring a high number of magnetically equivalent 19F-nuclei in a single macromolecule, adequate fluorine nucleus mobility, and excellent water solubility. This design utilizes superfluorinated polyphosphazene (PPz) polymers as the 19F-source; these are modified with sodium mercaptoethanesulfonate (MESNa) to achieve water solubility exceeding 360 mg/mL, which is a similar solubility to that of sodium chloride. We observed substantial signal enhancement in MRI with these novel macromolecular carriers compared to non-enhanced surroundings and aqueous trifluoroacetic acid (TFA) used as a positive control. In conclusion, these novel water-soluble macromolecular carriers represent a promising platform for future MRI contrast agents.

Enhanced Mucoadhesion of Thiolated β-Cyclodextrin by S-Protection with 2-Mercaptoethanesulfonic Acid.

This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with phosphorus pentasulfide resulting in a thiolated β-CD (β-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form β-CD-SS-MESNA. The structure of the novel excipient was confirmed by 1H NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of β-CD-SH, determined by Ellman's test, was 2281.00 ± 147 μmol/g, and it was decreased to 45.93 ± 19.40 μmol/g by S-protection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with β-CD-SH and β-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native β-CD, respectively. The unprotected β-CD-SH diffused to a lesser extent into the mucus than native β-CD, while S-protected β-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5- and 3.0-fold higher cellular uptake of β-CD-SH and β-CD-SS-MESNA, compared to the native one, was established on Caco-2 cell line by flow cytometry, respectively, causing slightly decreased cell viability. On account of the enhanced mucoadhesion, this higher cellular uptake does not affect the application potential of β-CD-SS-MESNA as an oral drug delivery system since the carrier remains in the mucus and does not reach the underlying epithelial layer. According to these results, the S-protection of β-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.

Mesna Improves Outcomes of Sulfur Mustard Inhalation Toxicity in an Acute Rat Model.

Inhalation of high levels of sulfur mustard (SM), a potent vesicating and alkylating agent used in chemical warfare, results in acutely lethal pulmonary damage. Sodium 2-mercaptoethane sulfonate (mesna) is an organosulfur compound that is currently Food and Drug Administration (FDA)-approved for decreasing the toxicity of mustard-derived chemotherapeutic alkylating agents like ifosfamide and cyclophosphamide. The nucleophilic thiol of mesna is a suitable reactant for the neutralization of the electrophilic group of toxic mustard intermediates. In a rat model of SM inhalation, treatment with mesna (three doses: 300 mg/kg intraperitoneally 20 minutes, 4 hours, and 8 hours postexposure) afforded 74% survival at 48 hours, compared with 0% survival at less than 17 hours in the untreated and vehicle-treated control groups. Protection from cardiopulmonary failure by mesna was demonstrated by improved peripheral oxygen saturation and increased heart rate through 48 hours. Additionally, mesna normalized arterial pH and pACO2 Airway fibrin cast formation was decreased by more than 66% in the mesna-treated group at 9 hour after exposure compared with the vehicle group. Finally, analysis of mixtures of a mustard agent and mesna by a 5,5'-dithiobis(2-nitrobenzoic acid) assay and high performance liquid chromatography tandem mass spectrometry demonstrate a direct reaction between the compounds. This study provides evidence that mesna is an efficacious, inexpensive, FDA-approved candidate antidote for SM exposure. SIGNIFICANCE STATEMENT: Despite the use of sulfur mustard (SM) as a chemical weapon for over 100 years, an ideal drug candidate for treatment after real-world exposure situations has not yet been identified. Utilizing a uniformly lethal animal model, the results of the present study demonstrate that sodium 2-mercaptoethane sulfonate is a promising candidate for repurposing as an antidote, decreasing airway obstruction and improving pulmonary gas exchange, tissue oxygen delivery, and survival following high level SM inhalation exposure, and warrants further consideration.

Supplementation of Sulfide or Acetate and 2-Mercaptoethane Sulfonate Restores Growth of the Methanosarcina acetivorans ΔhdrABC Deletion Mutant during Methylotrophic Methanogenesis

Methanogenic archaea are important organisms in the global carbon cycle that grow by producing methane gas. Methanosarcina acetivorans is a methanogenic archaeum that can grow using methylated compounds, carbon monoxide, or acetate and produces renewable methane as a byproduct. However, there is limited knowledge of how combinations of substrates may affect metabolic fluxes in methanogens. Previous studies have shown that heterodisulfide reductase, the terminal oxidase in the electron transport system, is an essential enzyme in all methanogens. Deletion of genes encoding the nonessential methylotrophic heterodisulfide reductase enzyme (HdrABC) results in slower growth rate but increased metabolic efficiency. We hypothesized that increased sulfide, supplementation of mercaptoethanesulfonate (coenzyme M, CoM-SH), or acetate would metabolically alleviate the effect of the ΔhdrABC mutation. Increased sulfide improved growth of the mutant as expected; however, supplementation of both CoM-SH and acetate together were necessary to reduce the effect of the ΔhdrABC mutation. Supplementation of CoM-SH or acetate alone did not improve growth. These results support our model for the role of HdrABC in methanogenesis and suggest M.acetivorans is more efficient at conserving energy when supplemented with acetate. Our study suggests decreased Hdr enzyme activity can be overcome by nutritional supplementation with sulfide or coenzyme M and acetate, which are abundant in anaerobic environments.

The utility of the CADISS® system in the dissection of epidural fibrosis in revision lumbar spine surgery (A case series)

This was a prospective, open label, observational case study. We enrolled 21 patients for revision spine surgery with the CADISS® System at two Belgium sites. The primary assessment was the number of successful removals of epidural fibrosis without cutting. The amount of MESNA used, total dissection and procedure time were recorded. For secondary criterion, the surgeons assessed global satisfaction, facilitation of dissection, quickness of action, usability, bleeding reduction and visualisation of the cleavage plane using an 11-point Likert scale (0-10). Due to the exploratory nature, no formal statistical analysis was planned. We calculated the percentage and confidence interval of successful procedures, the medians and corresponding interquartile range of the Likert criterion, and the mean (±SD) of the amount of MESNA used, CADISS® dissection time and total procedure time. 24 fibrosis dissections were performed in 19 patients and 23 were successful (95.8%, CI: 78.9%; 99.9%). The mean amount of MESNA used, mean dissection time and procedure time were 16ml (±4.94), 16.5min (±16.1) and 86.3min (±25.1), respectively. No dural tears were reported. The mean global satisfaction score was 9.0 (8.0-9.0). All other Likert criterion had scores of 8.0 or 9.0, excluding quickness of action, which scored 7.0 (6.0-9.0). The CADISS® System in revision spine surgery has potential to effectively reduce dissection complications.

Investigation of the adsorption performance and mechanism of 2-mercaptoethane sulfonic acid intercalated modified layered double hydroxide on heavy metal ions

In the adsorption process of functionalized layered double hydroxide (LDH) to target pollutants it, is essential to investigate the role of functional groups. In this work, 2‑mercaptoethane sulfonic acid (MS) was used as an intercalation modifier to prepare functionalized NiFe-LDH by solvothermal method. The interfacial interaction between the functional groups and the NiFe-LDH surface was studied via molecular dynamics simulation. During the intercalation process, the more negatively charged sulfonic acid group tends to self-assemble electrostatically with the LDH laminate, while the sulfhydryl group is involved in complexing heavy metal ions. The adsorption experiments showed that the adsorption performance of the adsorbent for the three ions of Cd2+, Mn2+, and Co2+ at 298.15 K was 266.16 mg/g, 175.60 mg/g, and 106.56 mg/g, respectively, which were 10 times, 8.7 times, and 4.9 times higher than that of unmodified NiFe-LDH. Meanwhile, Multiwfn wavefunction analysis combined Visual Molecular Dynamics (VMD) was applied to analyze and visualize the reaction active sites & the interactions between MS and NiFe-LDH, and the complexation of the functional group of MS with metal ions, to insight the role of the functional groups in MS molecule, and to reveal the cause that the adsorption capacity of modified NiFe-LDH for heavy metals greatly improves from the view of atoms.

The pathway for coenzyme M biosynthesis in bacteria

Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic archaea but is also associated with the anaerobic oxidation of methane to CO2 in anaerobic methanotrophic archaea and the oxidation of short-chain alkanes in Syntrophoarchaeum species. It has also been found in a small number of bacteria capable of the metabolism of small organics. Although many of the steps for CoM biosynthesis in methanogenic archaea have been elucidated, a complete pathway for the biosynthesis of CoM in archaea or bacteria has not been reported. Here, we present the complete CoM biosynthesis pathway in bacteria, revealing distinct chemical steps relative to CoM biosynthesis in methanogenic archaea. The existence of different pathways represents a profound instance of convergent evolution. The five-step pathway involves the addition of sulfite, the elimination of phosphate, decarboxylation, thiolation, and the reduction to affect the sequential conversion of phosphoenolpyruvate to CoM. The salient features of the pathway demonstrate reactivities for members of large aspartase/fumarase and pyridoxal 5'-phosphate-dependent enzyme families.

The Uroprotective Efficacy of Total Ginsenosides in Chinese Ginseng on Chemotherapy with Cyclophosphamide

Hemorrhagic cystitis is a recognizable complication of cyclophosphamide (CYP) attributable to its lively metabolite acrolein, which produces urothelial injury. The study intended to examine the uroprotective efficacy of total ginsenosides in Chinese ginseng (TGCG) in CYP-induced hemorrhagic cystitis. In total, 24 virgin female rats were randomized into four groups as follows: group 1 (control group; injected with normal saline), group 2 (injected with CYP plus a placebo with normal saline), group 3 (given CYP and TGCG (200 mg/kg)), and group 4 (given CYP and 2-mercaptoethane sulfonate sodium (Mesna, 30 mg/kg)). An evaluation by cystometry was conducted. Values of the voiding interval were assessed in anesthetized rats and histological examinations of the bladders were measured. In the cystometry analysis, the voiding interval was significantly reduced in the CYP group. TGCG and Mesna significantly increased in the voiding interval values, individually. Bladder edema and urothelial injury were examined after contact with CYP. Contrasted to the group given CYP, CYP-induced hemorrhagic cystitis, TGCG significantly increased the urothelial thickness, and significantly reduced scores of mucosal break and submucosal edema in the bladder. In conclusion, these findings mean that the treatment with TGCG in CYP rats can avoid hemorrhagic cystitis. TGCG decreases urothelial injury. TGCG may participate as the chief character of uroprotection in CYP-induced hemorrhagic cystitis.

A pseudotriangular layered platelet composed of silver 2-mercaptoethane sulfonate and its dual effects as pearlescent and antimicrobial pigments

Pearls have been highly valued as gemstones for thousands of years because of their unique and fascinating colors. However, it was difficult to harvest pearls in large quantities in nature due to their scarcity. Thus, there has been a steady demand for the development of artificial pearlescent pigments, and substrate-based pigments composed of mica substrates with coated metal oxide layers were introduced in the 1960s. Although these pigments remain the most common pearlescent pigments up to date, they have no other functions except for the pearlescent effect. Herein, we present novel micron-sized particles which are layered platelets with a unique pseudotriangular shape (triangular with concave sides and a bifurcated vertex) and composed of antimicrobial reagents, silver cations, and 2-mercaptoethane sulfonate anions. These particles exhibit both pearlescent and antimicrobial properties owing to their structure (layered platelets) and constituents (antimicrobial reagents), respectively. An additional advantage of these particles is that they can be prepared in one-pot process through a precipitation reaction by simply mixing two aqueous solutions containing silver cations and sodium 2-mercaptoethane sulfonate anions. These particles can potentially be used as pigments requiring both pearlescent and antimicrobial properties in the pigment field.

Infliximab and/or MESNA alleviate doxorubicin-induced Alzheimer's disease-like pathology in rats: A new insight into TNF-α/Wnt/β-catenin signaling pathway

AimsThe current study aimed to elucidate the neurotoxic potential of DOX to induce AD-like pathology paying attention to the role of wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway. A major aim was to evaluate the efficacy of infliximab (IFX) either individually or in combination with 2-mercaptoethane sulfonate sodium (MESNA) on the DOX-induced neurotoxicity in rats. MethodologyAD-like pathology was induced in adult male Wistar rats by intraperitoneal (i.p.) administration of DOX at a dose of 3.5 mg/kg twice a week for 3 weeks. DOX-injected rats were then treated with either INF at a single dose of 5 mg/kg i.p. (IFX group), MESNA at a dose of 160 mg/kg/day i.p. for 4 weeks (MESNA group) or their combination at the same specified doses (INF + MESNA group). At the end of the study period, behavioral assessment was performed and the brain tissue samples were harvested at sacrifice. Key findingsDOX-treated rats significantly exhibited AD-like brain injury, increased amyloid burden, enhanced neuroinflammation and apoptosis, and multifocal histological injury in the cerebral cortex with widespread vacuolations. IFX and MESNA significantly reversed all the aforementioned detrimental effects in the DOX-treated rats. SignificanceThe study has provided sufficient evidence of the potential of IFX and/or MESNA to ameliorate the DOX-induced neurotoxicity, with the best improvement observed with their combined administration. A new insight has been introduced into the critical role of Wnt/β-catenin activation.

Trimetazidine attenuates cyclophosphamide-induced cystitis by inhibiting TLR4-mediated NFκB signaling in mice

AimCyclophosphamide (CP)-induced cystitis is a challenging clinical problem involving inflammation and dysfunction of bladder. Trimetazidine (TMZ) is an anti-anginal drug with anti-oxidant and anti-inflammatory properties. We aimed to investigate the protective effects of TMZ in CP-induced cystitis via inhibiting TLR4/NFκB signaling. Main methodsBalb/c mice were administrated TMZ (10 or 20 mg/kg/day) intraperitoneally (i.p.) for 5 consecutive days before CP. On day 6, cystitis was induced by a single dose of CP (300 mg/kg, i.p.). Mesna (2-mercaptoethane sulfonate sodium; 30 mg/kg, i.p.) was administered 20 min before and at 4 and 8 h after the CP injection. After 24 h of cystitis induction, the bladders were removed for histopathological evaluation, contractility studies, biochemical analysis and western blotting. MTT assay was performed in a cancer cell line (MDA-MB-231) to evaluate the effect of TMZ on the cytotoxicity of CP. Key findingsCP-induced severe cystitis was confirmed by histological disturbances and the decrease in carbachol-evoked contractions of detrusor strips, which was partially improved by TMZ (20 mg/kg/day). SOD activity and GSH content were decreased whereas TNF-α and IL-1β levels were increased in the bladders of CP-treated mice, which were restored by TMZ or mesna. TMZ reduced the CP-induced increase in the protein expressions of caspase-3, TLR4 and phosphorylated-NFκB in bladder tissues. TMZ alone decreased the cell viability and TMZ also enhanced the cytotoxicity of CP. SignificanceOur study provides the first preclinical evidence that TMZ attenuates CP-induced urotoxicity by enhancing anti-oxidant capacity and suppressing inflammation possibly via downregulating TLR4-mediated NFκB signaling while augmenting the cytotoxicity of CP.

Mesna, an unusual agent causing hypersensitivity reactions during chemotherapy

Sodium 2-mercaptoethane sulfonate (mesna) is a detoxifying agent used to prevent hemorrhagic cystitis in patients receiving chemotherapy with either high-dose cyclophosphamide or ifosfamide. It has a reported half-life of 22 minutes, is quickly excreted by the kidneys after infusion, and accumulates in the bladder, where it detoxifies urotoxic breakdown products of cyclophosphamide and ifosfamide.1 Despite multiple reported dosage regimens, mesna is usually administered before or concomitant with the first dose of cyclophosphamide or ifosfamide, followed by bolus doses.

THE USE OF MULTISUBSTRATE MIXTURES FOR METHANE BIOSYNTHESIS BY AN ADAPTED COMPLEX OF MICROORGANISMS FOR OBTAINING ORGANIC FERTILIZER

Due to the istabiity of market prices for traditional hydrocarbon energy resources and negative impact of their combustion products on the environment, recently quite rapidly develop technology that provide for, first of all, renewable energy sources. One of the promising areas of alternative energy is bioenergy is a branch of biotechnology that considers organic matter of biomass of various origins (mainly agricultural waste) as a fuel source. Among the main advantages of energy biotechnology, it should be noted the speed and relative ease of recovery of the energy substrate, as well as the fact that it is not alien to the environment, so, even if released in quantities exceeding the permissible ones, this will not lead to irreversible changes in the ecosystem. Excess biomass will quickly be incorporated into biogeochemical cycles, which is the key to minimizing environmental damage. The process of bioconversion of methane from organic substrate compounds (carbohydrates, proteins, nucleic acids, lipids, organic acids, alcohols), which in three stages, is called methanogenesis. This process involves a specific complex bacterial enzyme system, consisting of the following coenzymes: methanofuran, tetrahydro-methanopterin, coenzymes F420 and F430, coenzyme M (CoM), coenzyme B. Using of ways of processing and waste disposal, that based on alternative biological recycling methods of organic pollutants does not always allow to achieve the expected effect, in particular on artificially created ecosystems of animal farms working in a closed mode. Concentration on a small area of a significant amount of biowaste (manure, dung, process runoffs etc.) of the cattle kept in the facilities of live-stock industry, contaminates soils, water bodies and atmospheric air with microorganisms, dust, harmful gases and other decomposition products. Often, it is one of the main factors constrainting on the growth of livestock enterprises and agro-industrial complex (AIC) capacities in general, restraining the economic development of regions specializing in agricultural production. For the first time in the region, study was carried out in order to determine the most efficient way to process miskantus phytomass for the production as target products of methane-containing biogas mixture and organo-mineral fertilizer suitable for use in agriculture and forestry. An economically and ecologically attractive way of utilization of wastes of phyto- and zoogenic origin, which makes it possible significantly reduce anthropogenic pressure on the environment, has been proposed.

Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry

Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some anti-cancer drugs (e.g., cyclophosphamide and ifosphamide). Also, it scavenges free radicals which cause numerous disorders by attacking biological molecules. Current methods available to analyze MESNA in biological matrices include colorimetry and high-performance liquid chromatography (HPLC) with ultraviolet, fluorescence, or electrochemical detection. These methods have several limitations including low sensitivity, poor selectivity, a high degree of difficulty, and long analysis times. Hence, a rapid, simple, and sensitive HPLC tandem mass spectrometry (MS/MS) method was developed and validated to quantify MESNA in rat plasma following IP administration. The analysis of MESNA was accomplished via plasma protein precipitation, centrifugation, supernatant evaporation, reconstitution, and HPLC-MS/MS analysis. The method showcases an outstanding limit of detection (20 nM), excellent linearity (R2 = 0.999, and percent residual accuracy >90%) and a wide linear range (0.05–200 μM). The method also produced good accuracy and precision (100 ± 10% and <10% relative standard deviation, respectively). The validated method was successfully used to analyze MESNA from treated animals and will allow easier development of MESNA for therapeutic purposes.