Mesna Group Research Articles

Treatment of temporomandibular joint internal derangement using MESNA injection

IntroductionThe development of temporomandibular disorders specifically emphasizes the biochemical changes occurring in the synovial fluid at different stages of temporomandibular joint disease. Research has indicated that inflammation may be a primary reason behind the pain and dysfunction in temporomandibular joint diseases. Since its clearance several years ago, MESNA (sodium 2-mercaptoethanesulfonate) has been used in various formulations as a mucolytic drug in the respiratory domain. It operates by disrupting the disulfide bonds present between polypeptide chains within mucus. MESNA exhibits minimal tissue distribution, with the material being swiftly and thoroughly eliminated via the kidneys.ObjectivesTo assess the efficacy of injecting MESNA directly into the Temporomandibular Joint to treat internal derangement.Materials and methodsA randomized clinical trial was conducted on sixty patients who exhibited non-responsiveness to conventional treatment and were diagnosed with TMJ anterior disc displacement with reduction. The patients were chosen from the outpatient clinic of the Oral and Maxillofacial Surgery Department at Tanta University Faculty of Dentistry. Two equal groups of patients were randomly assigned to each other. Group I (Mesna group) received intra-articular injection with MESNA solution. Group II (Standard group) received arthrocentesis with lactated ringer solution followed by injection of Hyaluronic Acid (HA). The data was gathered by functional examinations such as maximum interincisal opening (MIO) and clicking. A Visual Analogue Scale (VAS) assessed pain severity before and after treatments.ResultsBoth MESNA and HA showed significant improvement up to six months of the follow-up compared to preoperative status, as evidenced by better mouth opening, lateral excursion, lower clicking, and reduced pain score in patients with TMDs. MESNA showed significant improvement during follow-up compared to HA.ConclusionCompared to HA, MESNA showed a more noticeable improvement during the follow-up period.

Vocal Fold Submucosal Mesna Injection and Microflap Elevation in a Rabbit Model.

Mesna triggers chemical dissection in tissues by breaking down disulfide bonds and is used during surgical dissections in several areas. In this study, we aimed to investigate the effect of submucosal mesna infiltration on microflap elevation and the histopathological findings of its effects on the vocal fold lamina propria in a rabbit model. Eight adult male New Zealand white rabbits were used in the study. Each vocal fold was randomized, and 0.1 mL of mesna was injected into one-fold and 0.1 mL of saline to the contralateral fold. An incision was made on the epithelium and elevation was performed. The animals were sacrificed after two weeks, and the vocal folds were excised. Inflammatory response, fibrosis, and epithelial thickness were evaluated with hematoxylin eosin and Masson's Trichrome staining. Elevation time and histopathological features were compared between the two groups. The elevation time (20.9 ± 1.6 second) in the saline group was significantly higher (P < 0.05) than in the mesna group (15.0 ± 3.4 second). The inflammation (1.3 ± 0.5 vs. 1.1 ± 1.0, respectively) and fibrosis scores (1.0 ± 0.8 vs. 0.8 ± 0.7, respectively) did not differ significantly (P > 0.05 in both). Epithelial thickness (12.5 ± 4.7 vs. 10.3 ± 5.3, respectively) did not differ significantly (P ˃ 0.05) in the mesna and saline groups either. We determined that mesna facilitates the microflap elevation of the vocal folds in rabbits and does not damage the histological structure of vocal folds. This study encourages future studies to evaluate the use of mesna, now actively used across disciplines, in phonosurgery as well.

The assesment of intraoperative use of mesna in canal wall-up cholesteatoma surgery - preliminary report.

&lt;b&gt;Introduction:&lt;/b&gt; Surgery is still the method of choice in chronic otitis media with cholesteatoma. Except for some specific clinical situations, classic canal wall up technique (CWU), remains a gold standard as a primary treatment in most departments. Unfortunately, the risk of recurrence in such an approach is estimated at 9 to even 70%. This fact prompts researchers to look for ways to reduce those unfavourable statistics. One of the recognized methods supporting the removal of cholesteatoma is the intraoperative use of mesna (sodium 2-mercaptoethanesulfonate). This synthetic sulphur compound disrupts disulfide bridges in polypeptide chains, thanks to which it facilitates matrix preparation.&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Aim:&lt;/b&gt; To evaluate the effect of intraoperative use of mesna on the treatment outcomes in patients with chronic otitis media with cholesteatoma operated on by means of the canal wall up technique (CWU).&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Material and methods:&lt;/b&gt; 459 surgical reports of patients with middle ear cholesteatoma were analyzed. In total, 52 adult patients with no history of previous ear surgery operated on by means of the CWU technique by the same experienced otosurgeon with all follow-up data available were included in the study. Twenty-six were operated on with the use of mesna (mesna group) and 26 by means of the classic CWU technique (control / no-mesna group). There were 28 women and 24 men with a mean age of 41 years.&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Main Outcome Measure(s):&lt;/b&gt; Postoperative hearing results and cholesteatoma recidivism rate.&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Results:&lt;/b&gt; Overall recidivism rate was 21.15 %. It was higher in the no-mesna (26.9%) than in the mesna group (15.4%) - although the outcomes were better in the mesna group, the difference was not statistically significant (P = 0.49715). Hearing gain was better in the mesna than in the no-mesna group (10 dB vs 7 dB), but the difference was not statistically significant (P = 0.20089).&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Our preliminary results show that mesna reduces recidivism rates in patients with cholesteatoma. Further study with the analysis of a larger group of patients is needed to prove it statistically.

Evaluation of the Efficacy of Lactobacillus acidophilus in the Treatment of Cyclophosphamide-induced Hemorrhagic Cystitis in Wistar Rats.

Hemorrhagic cystitis is an inflammatory complication that can be caused by the administration of cyclophosphamide, which is widely used as an antineoplastic agent. In the search for new therapeutic alternatives, probiotics can suppress the inflammatory process and, therefore, can be used to prevent this disease. Thus, this study aimed to evaluate the effects of using Lactobacillus acidophilus NCFM in the treatment of cyclophosphamide-induced hemorrhagic cystitis in Wistar rats. Lactobacillus acidophilus NCFM (2x108 CFU) was used in the treatment of cyclophosphamide- induced hemorrhagic cystitis (200 mg/kg, intraperitoneal) in 77 female Wistar rats. Rats were distributed into experimental groups (n = 9): control group (GC), zero control group (GCZ), inflammation group (GI), 24-hour acute treatment groups: 24-hour lactobacilli treatment group (GL24H) and mesna group (GM), and 30-day chronic treatment groups: lactobacilli treatment group (GTL) and mesna+lactobacilli group (GM+L). After treatment, animals were euthanized and biological materials were collected for blood count, biochemical analyses, examination of abnormal sediment elements (EAS), and histopathological analysis. GI results showed development of edema, macroscopic alterations, and signs of bleeding in the bladder; in addition, lesions in the urothelium and hemorrhage were also found. GL24H and GM presented intact urothelium, without inflammatory reaction and hematological or biochemical urine alterations. Therefore, this study demonstrated that L. acidophilus presented uroprotective effect against the action of cyclophosphamide in both the short and long term.

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.

Evaluation of protective effects of mirtazapine and mesna on cisplatin-induced ovarian damage in rats

To evaluate whether mirtazapine and mesna have protective effects on cisplatin-induced ovarian injury. A total of 32 female Wistar Albino rats were divided into 4 groups (8 rats per group) and included in the study. No medication was administered to the first group; only intervention was that their ovaries were removed and anti-mullerian hormone (AMH) values were measured. The second group received intramuscular cisplatin at a single dose of 7.5 mg/kg. The third group received a single dose of 200 mg/kg mesna intraperitoneally, and 30 minutes later, a single dose of 7.5 mg/kg intramuscular cisplatin was administered. The fourth group received oral 30 mg/kg mirtazapine, and 60 minutes later, a single dose of 7.5 mg/kg intramuscular cisplatin was administered. Oral 30 mg/kg mirtazapine was continued for ten days. Ovaries and AMH values of all groups were evaluated at the end of tenth day. In the cisplatin group when compared to normal ovarian tissue total histopathological damage score increased (p=0.037), preantral follicle count decreased (p=0.003) and AMH levels decreased (p&lt;0.001). In the cisplatin + mesna group total ovarian damage score was also increased (p=0.005), preantral and antral follicles decreased (p&lt;0.001 and p=0.001, respectively), and AMH levels decreased (p&lt;0.001). In the cisplatin + mirtazapine group, total ovarian damage score (p&lt;0.001), preantral follicle count (p=0.002) and AMH values were decreased (p&lt;0.001). It was concluded that mesna and mirtazapine were not effective in preventing ovarian damage due to cisplatin.

A clinical and histopathological comparison of saline, adrenaline and 2-mercaptoethanesulfonate (MESNA) in mucoperichondrial elevation: which is superior?

SUMMARYObjectiveTo determine whether submucosal mesna (2-mercaptoethane sodium sulfonate) infiltration is superior to normal saline or adrenaline + lidocaine in mucoperichondrial hydrodissection.MethodsTwenty-one rabbits were administered adrenaline + lidocaine, saline or mesna. Bilateral septal mucoperichondrial flap elevations were performed following submucosal infiltration. The intraoperative bleeding amount, operation time, accessibility of the surgical plane, field quality and degree of mucoperichondrial injury were recorded. The three groups were compared histopathologically.ResultsThe amount of bleeding and duration of the operation were significantly higher and the accessibility of the surgical plane score was significantly lower in the saline group vs. the other groups (p < 0.05). The mucosal damage rate was significantly higher in the saline group compared with adrenaline + lidocaine (p < 0.05). The surgical field quality was significantly lower in the saline group compared with adrenaline + lidocaine (p < 0.05). The accessibility of the correct surgical plane score was significantly lower in the saline group compared with the adrenaline + lidocaine and mesna groups (p < 0.05). The amount of bleeding, duration of operation, surgical field quality and accessibility of the surgical plane did not differ significantly between the adrenaline + lidocaine and mesna groups (p > 0.05). The pericondrium thickness was significantly lower in the saline group than the other groups. Cartilage thickness was significantly higher in the saline group compared with the mesna group (p > 0.05).ConclusionUse of mesna instead of normal saline or adrenaline + lidocaine in septoplasty was not more advantageous in terms of intraoperative parameters. The adrenaline + lidocaine group was superior to normal saline for all intraoperative parameters. In conclusion, the use of adrenaline may be more advantageous in facilitating septal mucoperichondrium elevation due to its widespread use, low cost and superiority to physiological saline.

The Neuroprotective Effect of Mesna on Cisplatin-Induced Neurotoxicity: Behavioral, Electrophysiological, and Molecular Studies.

Peripheral neuropathy and cognitive impairments following cisplatin administration may interfere with the clinical usage of the drug. Mesna is a chemoprotective agent with anti-inflammatory and anti-oxidant effects. Our study aimed to investigate the protective effects of mesna against cisplatin-induced neurotoxicity. Neurotoxicity was induced by the administration of 2.5mg/kg cisplatin twice a week for four consecutive weeks in male Wistar rats. The neuroprotective effect of mesna (150mg/kg/day) was evaluated through behavioral, electrophysiological, and molecular studies. Cisplatin treatment caused passive avoidance memory impairment, increased anxiety-like behaviors, altered thermal sensitivity, and decreased muscle strength in a grip strength test. Our electrophysiological studies indicated that administration of cisplatin induced peripheral sensory neuropathy and decreased the amplitudes of the compound action potential of sensory nerves. Cisplatin administration increased MDA and 4-HNE levels and decreased anti-oxidant (SOD and GPx) enzymes. Proinflammatory cytokines (IL-1β and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were increased by cisplatin treatment. Morphological alterations were observed in the dorsal root ganglion (DRG) of cisplatin-treated rats. Cognitive impairments, anxiety, muscle strength, and thermal sensitivity changes induced by cisplatin were improved with mesna treatment. The reduced conduction velocity in sensory nerves was recovered in the cisplatin+mesna group. Mesna partially alleviated redox imbalance, reduced the proinflammatory cytokines, and MMP-2/9 levels. Mesna administration also relieved the morphological changes in DRG of cisplatin-treated rats. In conclusion, our results revealed that mesna can alleviate cisplatin-induced central and peripheral nervous system toxicity. These results support the concept that chemotherapy-induced neuropathy can be partially inhibited via mesna.

Incidence of hemorrhagic cystitis after cyclophosphamide therapy with or without mesna: A cohort study and comprehensive literature review.

Cyclophosphamide is an alkylating agent associated with significant toxicities, most importantly hemorrhagic cystitis. Many approaches including mesna use were established to reduce this toxicity. However, data on mesna efficacy are conflicting. To investigate the incidence of hemorrhagic cystitis in patients receiving cyclophosphamide therapy with or without mesna. A retrospective chart review was done on all adult patients receiving cyclophosphamide therapy with or without mesna at the King Saud University Medical City. The incidence of hemorrhagic cystitis was recorded. Patients receiving mesna were compared with those not receiving mesna. Data were reported as numbers and percentages, and appropriate statistical tests of association were used. This step was followed by a comprehensive literature review using appropriate keywords in PubMed from the inception of the database until August 2019. All studies of interest were reported. A total of 718 patients' medical records were reviewed. The majority of the patients received mesna (n = 433, 60%). The mesna group had a greater incidence of hemorrhagic cystitis (3.5% vs. 0.4%, p < 0.004) and received a significantly larger cumulative dose (3103 ± 1696 vs. 2465 ± 1528, p < 0.001) mg of cyclophosphamide therapy. Our literature review revealed large differences in the conclusions of published trials with highly diverse study designs and populations, emphasizing on the need of large prospective trials to address this topic.Conclusion and relevance: Our study results do not support the use of mesna in preventing hemorrhagic cystitis. We found that the only influential factor in the development of hemorrhagic cystitis was the dose of cyclophosphamide therapy.

Mesna Alleviates Cerulein-Induced Acute Pancreatitis by Inhibiting the Inflammatory Response and Oxidative Stress in Experimental Rats.

Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic inflammatory response and multiple organ failure. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis. This study is designed to investigate the possible effect of mesna on an experimental model of cerulein-induced acute pancreatitis. Animals were divided into five groups: Group 1 served as a control group given the saline; group II (mesna group) received mesna at a dose of (100mg/kg per dose, i.p.) four times; group III (acute pancreatitis group) received cerulein at a dose of (20µg/kg/dose, s.c.) four times with 1-h intervals; group VI, cerulein + mesna, was treated with mesna at a dose of (100mg/kg, i.p.) 15min before each cerulein injection. Animals with acute pancreatitis showed elevated serum amylase and lipase levels. Biochemical parameters showed increased pancreatic tumor necrosis factors-α (TNF-α) and interleukin-1β (IL-1β) levels. A disturbance in oxidative stress markers was evident by elevated pancreatic lipid peroxides (TBARS) and decline in pancreatic antioxidants' concentrations including reduced glutathione (GSH); superoxide dismutase (SOD); and glutathione peroxidase (GSH-Px). Histological examination confirmed pancreatic injury. Pre-treatment with mesna was able to abolish the changes in pancreatic enzymes, oxidative stress markers (TBARS, SOD, GSH and GSH-Px), pancreatic inflammatory markers (TNF-α, IL-1β) as well as histological changes. Mesna mitigates AP by alleviating pancreatic oxidative stress damage and inhibiting inflammation.

Chemically Assisted Dissection With Sodium 2-Mercaptoethanesulfonate (MESNA) in the Surgical Management of Pediatric Cholesteatoma.

To evaluate the effectiveness of the chemically assisted dissection with sodium 2-mercaptoethanesulfonate (MESNA), in the reduction of residual and recurrent cholesteatoma after mastoidectomy in children with chronic cholesteatomatous otitis media (CCOM). Retrospective case-control study. Tertiary referral center. One hundred forty mastoidectomies performed in patients under 18 years of age for the treatment of CCOM. Chemically assisted dissection (CAD) with MESNA compared with surgical dissection without MESNA. Recidivism of cholesteatoma (recurrence and residual disease), variations in the average of bone conduction threshold after treatment, and complications. Recidivism of cholesteatoma was significantly lower when CAD with MESNA was used (p < 0.0001). No difference was found in the mean variation of the average of bone conduction thresholds between the groups, confirming its safety profile regarding auditory function. Meatoplasty stenosis after surgery was more prevalent within CAD with MESNA group (p: 0.049). Recurrent and residual cholesteatoma remains a problem, especially in children and despite surgical techniques such as canal wall down mastoidectomy and endoscopic ear surgery. CAD with MESNA can be safe and effective to reduce recurrence rates. Multicenter and prospective studies with larger number of patients are needed to validate these findings. The higher rate of meatoplasty stenosis after CAD with MESNA merits additional clinical research to confirm these findings, as well as in vitro studies evaluating the effect of the drug on the activity of fibroblasts and other growth factors that may be involved.

ANTIFIBROTIC ACTIVITY OF MESNA AGAINST AMIODARONE-ASSOCIATED LUNG INJURY IN WISTAR RATS

Objective: Lung fibrosis is a progressive respiratory disease with a high percentage of mortality. Till now, it had bad prognosis to conventional medications. This study was designed to evaluate the role of mesna, the well-known antioxidant agent, against pulmonary fibrosis.Methods: Pulmonary fibrosis was induced by administration of amiodarone to Wistar rats. Lung indices, leukocytes count, oxidative stress markers, cytokines levels, and hydroxyproline contents, in addition to the histopathological tests, were done for control, amiodarone, and mesna plus amiodarone group.Results: The elevated ratio of lung/body weight and total leukocytes count within bronchoalveolar lavage fluid for amiodarone rats was decline significantly when cotreated with mesna therapy. Furthermore, mesna significantly brought down the lipid peroxidation of amiodarone in lung tissue, represented by decreasing malondialdehyde level and increasing superoxide dismutase (SOD) and catalase activity. In addition, mesna diminished the profibrotic transforming growth factor-β1 level while elevated the antifibrotic interferon-γ level, and the high activity of the enzyme matrix metalloproteinase-7 was restored within mesna group. Meanwhile, mesna counteracts the increment of hydroxyproline contents and Ashcroft grading scale within amiodarone group. Histologically, critical improvement in the inflammatory cell penetration and alveolar septa was seen in the lung tissue of rats within mesna group, contrasted with those received just amiodarone. Trichome staining clarified that collagen deposition was notably diminished in the peri-alveolar and peri-bronchial area within mesna group. Moreover, mesna therapy downregulated SMAD3 protein level, which was overexpressed by amiodarone challenge.Conclusion: This study gives evidence that mesna therapy may act as a protective agent against amiodarone-mediated pulmonary fibrosis.

ANTIFIBROTIC ACTIVITY OF MESNA AGAINST AMIODARONE-ASSOCIATED LUNG INJURY IN WISTAR RATS

Objective: Lung fibrosis is a progressive respiratory disease with a high percentage of mortality. Till now, it had bad prognosis to conventional medications. This study was designed to evaluate the role of mesna, the well-known antioxidant agent, against pulmonary fibrosis.Methods: Pulmonary fibrosis was induced by administration of amiodarone to Wistar rats. Lung indices, leukocytes count, oxidative stress markers, cytokines levels, and hydroxyproline contents, in addition to the histopathological tests, were done for control, amiodarone, and mesna plus amiodarone group.Results: The elevated ratio of lung/body weight and total leukocytes count within bronchoalveolar lavage fluid for amiodarone rats was decline significantly when cotreated with mesna therapy. Furthermore, mesna significantly brought down the lipid peroxidation of amiodarone in lung tissue, represented by decreasing malondialdehyde level and increasing superoxide dismutase (SOD) and catalase activity. In addition, mesna diminished the profibrotic transforming growth factor-β1 level while elevated the antifibrotic interferon-γ level, and the high activity of the enzyme matrix metalloproteinase-7 was restored within mesna group. Meanwhile, mesna counteracts the increment of hydroxyproline contents and Ashcroft grading scale within amiodarone group. Histologically, critical improvement in the inflammatory cell penetration and alveolar septa was seen in the lung tissue of rats within mesna group, contrasted with those received just amiodarone. Trichome staining clarified that collagen deposition was notably diminished in the peri-alveolar and peri-bronchial area within mesna group. Moreover, mesna therapy downregulated SMAD3 protein level, which was overexpressed by amiodarone challenge.Conclusion: This study gives evidence that mesna therapy may act as a protective agent against amiodarone-mediated pulmonary fibrosis.

Neutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide

Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which courses with neutrophil accumulation and affects 6–50% of patients depending on dose intensity. Here, we investigated the role of neutrophils in this inflammatory process. Female Swiss mice (n = 8/group) were injected with saline, IFO (400 mg/kg, i.p.), fucoidan (a P- and L-selectins inhibitor, 100 mg/kg, i.v.) or IFO + fucoidan (1–100 mg/kg) alone or combined with mesna (80 mg/kg i.p.). Another group of mice received anti-Ly6G antibody (500 μg/mouse, once daily for 2 days) for neutrophil depletion before IFO injection. In another experimental setting, animals received granulocyte colony-stimulating factor (G-CSF, 400 μg/kg), IFO (200 mg/kg), G-CSF (25–400 μg/kg, for 5 days) + IFO (200 mg/kg, i.p.) or fucoidan + G-CSF + IFO. Bladder injury was evaluated 12 h after IFO injection. IFO 400 mg/kg significantly increased visceral hyperalgesia, bladder edema, hemorrhage, vascular permeability, MPO, IL-1β and IL-6 tissue levels, and COX-2 immunostaining and expression versus the saline group (P < 0.05). Conversely, fucoidan (100 mg/kg) significantly attenuated these parameters compared to IFO-injected mice (P < 0.05). Additionally, fucoidan potentiated mesna protective effect when compared with IFO + mesna group (P < 0.05). Accordingly, neutrophil depletion with anti-Ly6G reduced inflammatory parameters and bladder injury compared to IFO (P < 0.05). In contrast, G-CSF enhanced IFO (200 mg/kg)-induced HC, which was significantly attenuated by treatment with fucoidan (P < 0.05). Therefore, neutrophils contribute to the pathogenesis of HC.

Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation.

Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation. A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation. The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups. Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.

Chemically assisted peroral endoscopic myotomy with submucosal mesna injection in a porcine model

Background: Peroral endoscopic myotomy (POEM) is a less invasive alternative to standard surgery for the treatment of achalasia. Previous studies have demonstrated that submucosal injections of mesna soften tissues and facilitate endoscopic submucosal dissection. Material and methods: We studied the technical feasibility of a chemically assisted POEM procedure with mesna injection (CA-POEM) in ten pigs compared with POEM with saline injection in five pigs. We also compared two dissection techniques in CA-POEM, diathermy needle knife dissection (n = 5) and balloon mechanical dissection (n = 5). A 10 cm esophageal submucosal tunnel was created with a needle knife or with balloon mechanical dissection following mesna or saline submucosal injection. Approximately 5 cm of inner circular muscle was then dissected within the tunnel. The tunnel was closed with endoclip application at the mucosal endoscopic entry point. Pigs were sacrificed one week post procedure. Results: All procedures were successful and all pigs survived for one week. Submucosal tunneling time was significantly shorter in the mesna group (363.8 sec for needle knife dissection and 294.2 sec for balloon dissection) than in the saline group (640 sec), regardless of the dissection method (p < 0.05). Conclusions: Our study demonstrated the technical feasibility of CA-POEM.

After myringotomy, can topical Mesna application be an alternative method to ventilation tube application?

Sodium-2-mercaptoethanesulfonate (Mesna) is a mucolytic substance that is also used for chemically assisted tissue dissection in otological surgery. We investigated the effects of Mesna as a chemical agent on the closing time of perforation of the eardrum in an experimental animal model. We performed simple myringotomy with a knife on 44 tympanic membranes of 22 rats. Four rats were excluded from the study because of serosity in their ears. Rats were divided into two study groups and a control group. These groups were the Mesna-administered group (Group A) (8 rats, 15 tympanic membranes), the saline-administered group (Group B) (8 rats, 14 tympanic membranes) and the control (native) group (6 rats, 11 tympanic membranes) (Group C). We applied Mesna locally for 20 min following myringotomy. Examination was made with an otoendoscope on days 1, 2, 3, 5, and 7, and patency rates were recorded. According to our results, we found that the closing time of the tympanic membrane was significantly longer in the Mesna group than in the saline administrated and native group. After myringotomy procedure, the application of a single dose of Mesna may contribute to the recovery duration of middle-ear pathologies by delaying the closing time of tympanic membrane perforation. However, Mesna cannot be an alternative method for the application of ventilation tubes.

A double-blind, block-randomized, placebo-controlled trial to identify the chemical assistance effect of mesna submucosal injection for gastric endoscopic submucosal dissection

Previous animal studies and a pilot clinical trial demonstrated that submucosal injection of a thiol compound called mesna could chemically soften connective tissues and thus facilitate endoscopic submucosal dissection (ESD). To evaluate whether mesna injection could reduce procedural times for gastric ESD. Double-blind, block-randomized, controlled trial. University hospital. A total of 101 patients with superficial gastric cancer indicated for ESD were enrolled and randomly assigned to either the mesna or control (saline solution) group. Traditional ESD was performed with a single bolus injection of mesna or saline solution. Time for submucosal dissection (TSD). En bloc resection was achieved for all lesions in the mesna group (53/53) and 51 of 52 lesions (98.08%) in the control group. TSD was not statistically different between the groups (18.62 ± 13.9 [mean ± SD] minutes for the mesna group and 24.58 ± 24.55 [mean ± SD] minutes for the control group; P = .128), and there were fewer time-consuming cases (times over 30 minutes) in the mesna group compared with controls (7/53 vs 15/52; P = .049). Multivariate regression analysis demonstrated that use of mesna, specimen size, and the presence of fibrous scars were significantly correlated with TSD (P < .05). Single-center study. TSD was not significantly different between the mesna and control injection groups, but multivariate analysis indicated that mesna injection reduced procedural challenges associated with the submucosal dissection. ( UMIN000003786.).

Endoscopic submucosal dissection with a flexible Maryland dissector: randomized comparison of mesna and saline solution for submucosal injection (with videos)

Endoscopic submucosal dissection (ESD) is increasingly used for en bloc removal of GI lesions. Current ESD techniques have limitations including long procedure times, technical difficulty, and complications. To compare mesna with saline solution for ESD. Blinded, randomized, controlled, porcine study in live animals. Animal laboratory. Twelve gastric lesions were marked by using electrocautery. After submucosal injection, a circumferential mucosal incision was created, and ESD was performed by using a flexible Maryland dissector. Half of the ESDs were performed with submucosal injection of mesna. Primary outcome was the time to dissect the submucosal plane. Secondary outcomes were total ESD time, specimen size, and procedure related complications. The average (± SD) time for dissecting the submucosal plane was 15 minutes (range 10-22 ± 4.8 min) in the group with submucosal mesna injection and 16 minutes (range 8-29 ± 8.3 min) in the control group (P = 1.0). Complete en bloc resection including all of the electrocautery markings was achieved in all cases. Injection of mesna did not provide any benefit over saline solution in terms of overall ESD time (24 ± 7.3 min vs 28 ± 11 min; P = .42). There were no perforations. Four hemorrhages requiring intervention were encountered during the procedures in the control group, compared with no bleeding in the mesna group (P = .09). Animal model, limited sample size. Submucosal mesna injection did not affect procedure times but was associated with a trend toward a lower incidence of intraprocedural bleeding.

MESNA (sodium 2-mercaptoethanesulfonate) for prevention of contrast medium-induced nephrotoxicity – controlled trial

The purpose of this study was to examine the efficacy of sodium 2-mercaptoethanesulfonate (MESNA), a reactive oxygen scavenger, in at-risk patients given radiographic contrast agents. Contrast-induced nephropathy (CIN) is a common complication of radiographic procedures; reactive oxygen species (ROS) could play a key role. We conducted a randomized, double-blinded, placebo-controlled trial in 100 patients with stable serum creatinine levels ≥ 150 µmol/l. They received an infusion of either 1,600 mg of MESNA (n = 51) or placebo (n = 49) plus 0.9% saline prior to and after contrast administration. CIN was defined as a ≥ 25% increase in serum creatinine after 48 h compared to baseline. CIN occurred in 7 patients in the placebo group and none in the MESNA group (p = 0.005). The adjusted odds ratio for CIN was 0.17 (95% confidence interval 0.03 - 0.80, p = 0.026) in the MESNA group compared to the placebo group. Cystatin C concentrations decreased slightly in the MESNA group but increased in the control group (p < 0.05). MESNA plus volume expansion before and during contrast exposure was effective in this single-center study for preventing CIN compared to volume expansion alone.