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Background: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported., Methods: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality., Results: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies., Conclusion: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Surgical interventions are recommended for cases of advanced mitral regurgitation, however, limited facilities are available. The most prominent complication in such procedures is heparin‐derived bleeding. An alternative anticoagulant to heparin, nafamostat mesilate (NM), can reduce the occurrence of complications associated with heparin such as bleeding or shock. Objectives: This study aimed to evaluate the utility and safety of using NM during anaesthesia in canines. Methods: Six healthy adult Beagle dogs were anaesthetised, and NM was administered intravenously as a 10 mg/kg bolus dose over 5 min, followed by a continuous infusion of 10 mg/kg/h over 20 min. Blood tests and blood pressure measurements were performed at 0, 5, 25 and 55 min after NM administration. Results: Activated thromboplastin times at 0, 25 and 55 min were 13.0 ± 0.7 s, 106.7 ± 13.3 s and 28.2 ± 2.9 s, respectively, with a significant difference between 0 and 25 min (p < 0.01) only. No significant differences were observed in prothrombin time, antithrombin, fibrinogen and fibrin degradation product concentrations between timepoints. Activated clotting times (ACTs) at 0, 5, 25 and 55 min were 119.5 ± 9.6 s, 826.7 ± 78.6 s, 924.8 ± 42.4 s and 165.2 ± 13.5 s, respectively. Significant differences were observed between 0 and 5 min (p < 0.05) and between 0 and 25 min (p < 0.05). Blood pressure changes occurred in four dogs (66.7%). No other serious adverse effects were observed. Conclusions: ACT results indicated that NM use in anaesthetised healthy dogs was sufficient to obtain procedural anticoagulation with minimal adverse effects. However, these preliminary data require validation in further studies on cardiopulmonary bypass surgery. [ABSTRACT FROM AUTHOR]

Summary: Aim: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. Methods: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat. Hematoxylin and eosin staining (H&E staining) and Luxol fast blue (LFB) staining were used to observe the histological lesions. Apoptosis was examined by TUNEL staining, Annexin V‐FITC/PI, caspase‐3, and Bcl‐2. Cytokines and neurotrophins were tested by Western blot. Locomotion recovery assessed by hindlimb BBB score and the inclined plane test. Results: Nafamostat mesilate treatment significantly improved locomotion recovery as assessed by hindlimb BBB scores and the inclined plane test. H&E staining and LFB staining showed a significant increase in spared tissue in both gray matter and white matter. NM decreased the expression of the proinflammatory cytokines TNF‐α and IL‐6. In addition, apoptosis was also significantly decreased, as shown by TUNEL staining and Annexin V‐FITC/PI and by Western blotting for caspase‐3 and Bcl‐2 expression. Due to the mechanism of action of NM as a serine protease inhibitor, the drug decreased thrombin expression in the damaged spinal cord. Furthermore, NM increased the expression of neurotrophins (NT‐3, BDNF, and NGF). Conclusions: Upon NM treatment, the functional and histological outcomes were improved, and microenvironment upon SCI was modulated. As a clinically approved drug, NM holds promise for clinical use after spinal cord injury. [ABSTRACT FROM AUTHOR]

Nafamostat mesilate is the first anticoagulant of choice for leukocytapheresis (LCAP) with a Cellsorba E column for treating ulcerative colitis (UC). However, because of complications, mainly due to allergy to nafamostat mesilate, heparin may be used as a substitute. To evaluate the safety and tolerability of nafamostat mesilate and heparin as anticoagulants in LCAP for UC, we conducted post hoc analysis of data from a large-scale, prospective, observational study of LCAP, which was conducted at 116 medical facilities in Japan between May 2010 and December 2012. Of 832 patients included in this analysis, nafamostat mesilate and heparin were used in 676 (81.3%) and 113 (13.6%), respectively. There were no significant differences in the incidence of adverse reactions (8.6% vs. 7.1%) and intrafilter pressure increases (12.7% vs. 16.8%) between the nafamostat mesilate and heparin groups. Adverse reactions of hemorrhage or blood pressure decreases associated with heparin use were not observed. There were no significant differences in rates of clinical remission (69.1% vs. 68.1%) and mucosal healing (62.9% vs. 63.6%) between the nafamostat mesilate and heparin groups. Thus, the safety and tolerability were comparable in the nafamostat mesilate and heparin groups, indicating that both nafamostat mesilate and heparin can be well tolerated as anticoagulants in LCAP for UC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate nafamostat mesilate (NM) as an alternative anticoagulant agent for intermittent hemodialysis (IHD). Design: Prospective randomized study. Setting: University teaching hospital. Animals: Eighteen healthy Beagle dogs. Interventions: In group 1 (n = 6), NM was administered at a dose of 0.5 mg/kg/h during IHD for 5 hours. In group 2 (n = 6), NM was administered at a low dose of 0.25 mg/kg/h during IHD. In group 3 (n = 6), which was the control group, unfractionated heparin (UFH) was administered during IHD. The evaluated parameters included: the amount of residual blood clots in the blood chamber and arterial side of the dialyzer; the levels of hemoglobin, hematocrit, and platelets; and the prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT). Measurements and Main Results: Groups 1 and 2 successfully completed IHD without serious coagulation in the extracorporeal circulation. The residual blood clotting in the blood chamber and arterial side of the dialyzer did not significantly differ in groups 1 and 2 compared to group 3 (group 1 vs group 3, P = 1.000; and group 2 vs group 3, P = 1.000). No significant differences were observed between pre‐ and posttreatment PTs in groups 1 (P = 0.476) and 2 (P = 0.597), between pre‐ and posttreatment aPTTs in groups 1 (P = 0.983) and 2 (P = 0.977), and between pre‐ and posttreatment ACT in groups 1 (P = 0.282) and 2 (P = 0.401). In group 3, a significant elevation of ACT was observed at the posttest (P < 0.001). Conclusions: The results of this study in healthy Beagle dogs suggest that NM at 0.25 mg/kg/h may be a valid alternative to UFH for IHD. Further studies are needed in patients at high risk of bleeding. [ABSTRACT FROM AUTHOR]

Background: Differentiation between functional dyspepsia and early chronic pancreatitis is difficult because these diseases do not produce specific abnormalities in laboratory testing. The aim of this study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against functional dyspepsia and to characterize patients with favorable responses. Methods: Dyspeptic patients who exhibited no abnormalities on laboratory blood and urine testing, abdominal ultrasonography and upper gastrointestinal endoscopy were randomized to receive camostat mesilate 200 mg three times daily or famotidine 20 mg twice daily for 4 weeks. Symptoms severity was recorded before and at 2 and 4 weeks after starting treatment using a visual analog scale. Results: Epigastralgia was significantly improved after 2 and 4 weeks of treatment in both groups ( P < 0.01); this improvement tended to be more marked in the camostat mesilate group ( P < 0.05 at 2 weeks). The beneficial effect of camostat mesilate on epigastralgia was more prominent in chronic alcohol drinkers at 2 weeks ( P < 0.05) and 4 weeks ( P < 0.01). Conclusions: Camostat mesilate is superior to famotidine for relieving epigastralgia in patients with functional dyspepsia. Its pain-relieving effect is greater in patients who habitually drink alcohol. [ABSTRACT FROM AUTHOR]

Aims Eribulin mesilate is an inhibitor of microtubule dynamics that is approved for the treatment of late-stage metastatic breast cancer. Neutropenia is one of the major dose-limiting adverse effects of eribulin. The objective of this analysis was to develop a population pharmacokinetic-pharmacodynamic model for eribulin-associated neutropenia. Methods A combined data set of 12 phase I, II and III studies for eribulin mesilate was analysed. The population pharmacokinetics of eribulin was described using a previously developed model. The relationship between eribulin pharmacokinetic and neutropenia was described using a semi-physiological lifespan model for haematological toxicity. Patient characteristics predictive of increased sensitivity to develop neutropenia were evaluated using a simulation framework. Results Absolute neutrophil counts were available from 1579 patients. In the final covariate model, the baseline neutrophil count ( ANC0) was estimated to be 4.03 × 109 neutrophils l−1 [relative standard error ( RSE) 1.2%], with interindividual variability ( IIV, 37.3 coefficient of variation % [CV%]). The mean transition time was estimated to be 109 h ( RSE 1.8%, IIV 13.9 CV%), the feedback constant (γ) was estimated to be 0.216 ( RSE 1.4%, IIV 12.2 CV%), and the linear drug effect coefficient ( SLOPE) was estimated to be 0.0451 μg l−1 ( RSE 3.2%, IIV 54 CV%). Albumin, aspartate transaminase and receival of granulocyte colony-stimulating factor ( G-CSF) were identified as significant covariates on SLOPE, and albumin, bilirubin, G-CSF, alkaline phosphatase and lactate dehydrogenase were identified as significant covariates on mean transition time. Conclusions The developed model can be applied to investigate optimal treatment strategies quantitatively across different patient groups with respect to neutropenia. Albumin was identified as the most clinically important covariate predictive of interindividual variability in the neutropenia time course. [ABSTRACT FROM AUTHOR]

Patients who undergo renal replacement therapy often exhibit a high plasma linezolid concentration. Linezolid is metabolized via oxidation. Nafamostat mesilate has antioxidant effects and is frequently used as an anticoagulant during renal replacement therapy. We aimed to investigate the effect of nafamostat mesilate on plasma linezolid concentration. We examined whether the co‐administration of linezolid and nafamostat had any effect on plasma linezolid concentration. Mice were randomly allocated to two groups (n = 18/group): linezolid (100 mg kg−1, subcutaneous injection) + nafamostat (30 mg kg−1, intraperitoneal injection) and linezolid + saline. At 5 hours, the linezolid concentration was significantly higher in the linezolid + nafamostat co‐administration group than that in the linezolid + saline group (20.6 ± 9.8 vs 3.6 ± 1.2 μg/mL, respectively P <.001). The antioxidant effects of nafamostat may inhibit linezolid metabolism, resulting in the adverse event of high linezolid concentration if both are administered concurrently during renal replacement therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: Inflammation plays a pivotal role in liver injury. Gabexate mesilate (GM, a protease inhibitor) inhibits inflammation by blocking various serine proteases. This study examined the effects of GM on hepatic encephalopathy in rats with acute and chronic liver failure. Methods: Acute and chronic liver failure (cirrhosis) were induced by intraperitoneal TAA administration (350 mg/kg/day for 3 days) and common bile duct ligation, respectively, in male Sprague-Dawley rats. Rats were randomized to receive either GM (50 mg/10 mL/kg) or saline intraperitoneally for 5 days. Severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters, mean arterial pressure and portal pressure, were measured (only in chronic liver failure rats). Plasma levels of liver biochemistry, ammonia, nitrate/nitrite, interleukins (IL) and tumor necrosis factor (TNF)-α were determined. Results: In rats with acute liver failure, GM treatment significantly decreased the plasma levels of alanine aminotransferase ( P = 0.02), but no significant difference of motor activity, plasma levels of ammonia, IL-1β, IL-6, IL-10 and TNF-α or survival was found. In chronic liver failure rats, GM significantly lowered the plasma TNF-α levels ( P = 0.04). However, there was no significant difference of motor activity, other biochemical tests or survival found. GM-treated chronic liver failure rats had higher portal pressure ( P = 0.04) but similar mean arterial pressure in comparison with saline-treated rats. Conclusions: Chronic GM treatment does not have a major effect on hepatic encephalopathy in rats with TAA-induced acute liver failure and rats with chronic liver failure induced by common bile duct ligation. [ABSTRACT FROM AUTHOR]

Background: Constitutive activation of nuclear factor kappa-B (NF-κB) contributes to the aggressive behavior of pancreatic cancer. Over-expression of downstream target genes of NF-κB such as intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) leads to the promotion of cell adhesion, angiogenesis, invasion and metastasis. We previously reported that nafamostat mesilate, a synthetic serine protease inhibitor, blocks NF-κB activation in pancreatic cancer. We hypothesized that nafamostat mesilate may inhibit cell adhesion, angiogenesis, invasion and metastases in peritoneal dissemination of pancreatic cancer. Methods: In vitro, we assessed inhibition of NF-κB, phosphorylated IκBα, ICAM-1, VEGF and MMP-9 activity by nafamostat mesilate using human pancreatic cancer cell lines (AsPC-1, BxPC-3 and PANC-1). Changes in adhesion and invasion abilities of cancer cells were then evaluated by nafamostat mesilate treatment. In vivo, the efficacy of nafamostat mesilate treatment was assessed using peritoneal dissemination of pancreatic cancer in mice. Results: In vitro, nafamostat mesilate inhibited activities of NF-κB, phosphorylated IκBα, ICAM-1, VEGF and MMP-9. Moreover, nafamostat mesilate not only inhibited cell adhesion and invasion but also increased the sensitivity of anoikis. In vivo, tumor growth using AsPC-1 cells of the treatment group was significantly slower, and survival rate was significantly better, than those in control group ( p < 0.05). Conclusion: Nafamostat mesilate reduced peritoneal metastasis and prolonged survival of pancreatic cancer-bearing mice. [ABSTRACT FROM AUTHOR]

Background: Nafamostat mesilate (NM), a protease inhibitor, is available for acute pancreatitis and disseminated intravascular coagulopathy and is used as an anticoagulant for haemodialysis in Japan. Co-infusion of red cell concentrates (RCC) and intravenous drugs is usually contraindicated. Because of limited venous access, adherence to the guidelines may be compromised in some clinical settings. Therefore, we investigated the influence of co-infusion of RCC and various anticoagulants on haemolysis in vitro. Methods: We investigated the effect of co-incubation of RCC and various anticoagulant drugs [NM, gabexate mesilate (GM), heparin] in packed erythrocytes. We evaluated haemolysis using lactate dehydrogenase and free haemoglobin. In addition, we also evaluated the influence of co-incubation on phosphatidylserine (PS) expression on the erythrocyte membrane. Results: GM and NM induced haemolysis in a dose-dependent manner, which was inhibited by removal of citrate and pretreatment with the calcium chelator, ethylenediaminetetraacetic acid. In a dynamic experiment using an infusion pump, NM not only induced haemolysis during co-infusion with RCC but also elevated PS expression dependent on extracellular calcium. Conclusion: NM and GM induce haemolysis in packed erythrocytes in the presence of citrate that is dependent on extracellular calcium. [ABSTRACT FROM AUTHOR]

Tagawa T. Protease inhibitor nafamostat mesilate attenuates complement activation and improves function of xenografts in a discordant lung perfusion model. Xenotransplantation 2011; 18: 315-319. © 2011 John Wiley & Sons A/S. Abstract: Background: Anti-complement activity of nafamostat mesilate (FUT-175) is strong including its variety of pharmacological effects. The effect of FUT-175 for xenografts in an ex vivo guinea pig-to-rat lung perfusion model was evaluated. Methods: Heparinized Lewis rat blood was used to perfuse the lungs in three groups (n = 6 each). Group I used Lewis rat left lung for donor, Group X used guinea pig left lung for donor, and Group XF used guinea pig left lung for donor, which was perfused with Lewis rat blood with 0.2 mg/ml of FUT-175. Complement activity causing 50% hemolysis (CH50) in the perfusion blood and pulmonary function either before or during perfusion were serially measured. Pathological assessments of the lungs were also carried out after perfusion. Results: The duration of satisfactory pulmonary function was significantly increased in Group XF. Complement activity causing 50% hemolysis in Group XF decreased more significantly compared to Group X. FUT-175 suppressed both the increase in pulmonary arterial pressure and airway resistance, and the decrease in dynamic lung compliance. In Group X, pathology showed intra-alveolar hemorrhage, perivascular edema, and medial thickening with endothelial swelling of the pulmonary arteries. In Group XF, less changes were observed compared to Group X. Group X showed deposition of IgM, IgG, and C3 at the endothelium of arteries, which was fewer in Group XF, and even fewer in Group I. Conclusions: This study suggests that FUT-175 inhibited complement activation and improved lung xenograft function. FUT-175 ameliorates hyperacute rejection in a guinea pig-to-rat ex vivo xenogeneic lung perfusion model. [ABSTRACT FROM AUTHOR]

1. Direct haemoperfusion through a network of fibres immobilizing polymyxin B (PMX-B) is used for the treatment of septic shock, but the mechanism underlying its clinical benefits remains unclear. The aims of the present study were to assess the actions of direct haemoperfusion through fibres immobilizing PMX-B (PMX-DHP) on the effects of exogenously administered endotoxin in conscious guinea-pigs and to examine the difference in the effects of heparin compared with nafamostat mesilate (NM) used as an anticoagulant. Although nafamostat is widely used in Japan, the agent cannot necessarily be used elsewhere in the world. Therefore, the study aimed to investigate and elucidate the effectiveness of NM compared with heparin. 2. Colonic motion was monitored continuously via telemetry using a force transducer attached to the taenia caecum, whereas blood pressure was monitored using a carotid artery catheter. To establish a haemoperfusion circuit in each freely moving and conscious guinea-pig, catheters were implanted in the carotid artery and the jugular vein, tunnelled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (LPS; Escherichia coli, O111:B4; 1 mg/kg) was administered i.v. and PMX-DHP was conducted for 2 h. Heparin (50 IU/h) or NM (0.4 mg/h) was used as the anticoagulant. Furthermore, guinea-pigs were administered a lethal dose of LPS (10 mg/kg) and the survival rate was examined for animals undergoing PMX-DHP compared with control animals. 3. In guinea-pigs treated with PMX-DHP, relaxation of colonic longitudinal muscle caused by LPS was significantly suppressed, as were decreases in blood pressure. Of the two anticoagulants used, NM was more effective than heparin. In addition, PMX-DHP significantly increased the survival rate of guinea-pigs that received potentially lethal doses of LPS. 4. In ca onscious and unrestrained guinea-pig endotoxaemia model, PMX-DHP significantly improved intestinal paralysis and decreases in blood pressure. These effects were augmented more by NM than by heparin when an anticoagulant was used in the perfusion process. These findings suggest that haemoperfusion using PMX and NM performed in the early stage of endotoxaemia is an effective treatment. [ABSTRACT FROM AUTHOR]

Leukemia cutis is a localized or disseminated skin infiltration by leukemic cells. A 64-year-old man was diagnosed with acute myeloid leukemia (AML) complicated by disseminated intravascular coagulation. During the course of treatment with gabexate mesilate, the substance accidentally leaked from the infusion site in his elbow. One month later, a dark red erythema and induration accompanied by severe pain appeared in the area proximal to the gabexate mesilate injection site. The biopsy specimen demonstrated not only inflammation but infiltration of leukemic cells as well. Immunohistochemical staining for intercellular adhesion molecule-1 and platelet/endothelial cell adhesion molecule-1 showed strong expression of endothelial cells and leukemic cells. We speculate that the gabexate mesilate might have played a role in the induction of leukemia cutis via adhesion molecules in our case. [ABSTRACT FROM AUTHOR]

Aims: Eribulin mesilate is an inhibitor of microtubule dynamics that is approved for the treatment of late-stage metastatic breast cancer. Neutropenia is one of the major dose-limiting adverse effects of eribulin. The objective of this analysis was to develop a population pharmacokinetic-pharmacodynamic model for eribulin-associated neutropenia., Methods: A combined data set of 12 phase I, II and III studies for eribulin mesilate was analysed. The population pharmacokinetics of eribulin was described using a previously developed model. The relationship between eribulin pharmacokinetic and neutropenia was described using a semi-physiological lifespan model for haematological toxicity. Patient characteristics predictive of increased sensitivity to develop neutropenia were evaluated using a simulation framework., Results: Absolute neutrophil counts were available from 1579 patients. In the final covariate model, the baseline neutrophil count (ANC0) was estimated to be 4.03 × 10(9) neutrophils l(-1) [relative standard error (RSE) 1.2%], with interindividual variability (IIV, 37.3 coefficient of variation % [CV%]). The mean transition time was estimated to be 109 h (RSE 1.8%, IIV 13.9CV%), the feedback constant (γ) was estimated to be 0.216 (RSE 1.4%, IIV 12.2CV%), and the linear drug effect coefficient (SLOPE) was estimated to be 0.0451 μg l(-1) (RSE 3.2%, IIV 54CV%). Albumin, aspartate transaminase and receival of granulocyte colony-stimulating factor (G-CSF) were identified as significant covariates on SLOPE, and albumin, bilirubin, G-CSF, alkaline phosphatase and lactate dehydrogenase were identified as significant covariates on mean transition time., Conclusions: The developed model can be applied to investigate optimal treatment strategies quantitatively across different patient groups with respect to neutropenia. Albumin was identified as the most clinically important covariate predictive of interindividual variability in the neutropenia time course., (© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.)

Summary Background : Human immunodeficiency virus (HIV)-associated pancreatic alterations are frequent, but poorly investigated, notwithstanding their potential consequences on the course and management of HIV infection. No epidemiological or clinical data on pancreatic alterations have been published since the introduction of highly active antiretroviral therapy, and no indications of the pharmacological management of symptomatic or prolonged laboratory pancreatic abnormalities have been reported. Aim : To investigate the therapeutic role of gabexate mesilate and octreotide in HIV-infected patients with elevated, symptomatic or instrumentally confirmed pancreatic anomalies persisting for more than 3 months. Methods and results : An open-label, prospective, 5-year case–control study was conducted involving 185 consecutive patients with pancreatic alterations. Treatment of patients with severe laboratory and/or clinical involvement with low-dose gabexate mesilate and/or somatostatin was effective and safe and led to a lower recurrence rate and a better tolerability of concomitant drug regimens compared with supportive therapy taken by control patients. Combined gabexate–octreotide proved to be more active than single drug administration. Conclusions : Epidemiological and therapeutic data on the frequency, risk factors and clinical significance of pancreatic abnormalities during HIV infection are required, as are studies investigating the need for and choice of antisecretory and/or antiprotease compounds. [ABSTRACT FROM AUTHOR]

Present electron microscopical and immunocytochemistrical studies elucidated some morphological relationship between intercalated duct (ICD) and pancreatic islet cells in the chicken in streptozotocin (STZ) and/or camostat mesilate (CM) administrations. Twenty-one chickens were set into four experimental groups: (1) control group, (2) STZ administration group, (3) CM administration group, and (4) STZ + CM administration group. Cytoplasms of ICD cells stained more strongly with eosin in STZ administration group than other groups, and electron-dense materials and intercalated processes between ICD and islet cells were also increasing in time dependence in STZ administration. Number of pancreatic islet in STZ + CM co-administration was about 3.1 times larger than other groups. Many small sized cells were detected at surrounding area of ICD and they incorporated 5-bromo-2'deoxyuridine better than other experimental groups. Present morphological data suggested that ICD cells might support some tolerances of pancreatic endocrine cells against toxic substances and also involve in regeneration of new pancreatic islet cells in STZ + CM co-administration. [ABSTRACT FROM AUTHOR]

(1) Intravenous injection of ioxaglate (4 g iodine kg(-1)), an iodinated radiographic contrast medium, caused a marked protein extravasation, pulmonary oedema and a decrease in the arterial partial oxygen pressure in rats. (2) All of these reactions to ioxaglate were reversed by the pretreatment with gabexate mesilate (10 and 50 mg kg(-1), 5 min prior to injection) or nafamostat mesilate (3 and 10 mg kg(-1)), in which the inhibition was complete after injection of nafamostat mesilate (10 mg kg(-1)). (3) Both gabexate mesilate and nafamostat mesilate inhibited the activity of purified human lung tryptase, although the latter compound was far more potent than the former. (4) Ioxaglate enhanced the nafamostat-sensitive protease activity in the extracellular fluid of rat peritoneal mast cell suspensions. (5) Tryptase enhanced the permeability of protein through the monolayer of cultured human pulmonary arterial endothelial cells. Ioxaglate, when applied in combination with rat peritoneal mast cells, also produced the endothelial barrier dysfunction. These effects of tryptase and ioxaglate were reversed by nafamostat mesilate. (6) Consistent with these findings, immunofluorescence morphological analysis revealed that tryptase or ioxaglate in combination with mast cells increased actin stress fibre formation while decreasing VE-cadherin immunoreactivity. Both of these actions of tryptase and ioxaglate were reversed by nafamostat mesilate. (7) These findings suggest that tryptase liberated from mast cells plays a crucial role in the ioxaglate-induced pulmonary dysfunction. In this respect, nafamostat mesilate may become a useful agent for the cure or prevention of severe adverse reactions to radiographic contrast media. [ABSTRACT FROM AUTHOR]

We examined whether AN69ST (acrylonitrile and methallyl sulfonate copolymer) membranes adsorb nafamostat mesilate. This study retrospectively analyzed 87 continuous hemodiafiltration sessions in vivo. We divided the continuous hemodiafiltration sessions into AN69ST and non-AN69ST groups using the nafamostat mesilate dose and activated clotting time as indicators of nafamostat mesilate adsorption onto the membrane. Furthermore, we studied the in vitro adsorption of nafamostat mesilate from nafamostat mesilate solutions onto four different hemodialysis membranes. This in vivo study shows that nafamostat mesilate doses were significantly higher, but activated clotting times were shorter ( P < 0.001) in the AN69ST group than in the non-AN69ST group. These results suggest that AN69ST adsorbs nafamostat mesilate. Further, the in vitro experiments show that nafamostat mesilate adsorbs AN69ST on membranes significantly more than the other membranes tested. These in vitro and clinical findings provide evidence that AN69ST may adsorb nafamostat mesilate. [ABSTRACT FROM AUTHOR]

Objectives: Fatigue is a complaint frequently encountered among patients with Parkinson's disease (PD). Considering the possible relationship between fatigue and dopaminergic dysfuncion, we investigated the effect of pergolide mesilate (a D2 and D1 dopamine receptor agonist) and bromocriptine (a D2 selective dopamine receptor) in patients with PD. Methods: We evaluated 41 patients with PD and controls. We assessed the degree of fatigue by using a fatigue scale. The severity of PD was evaluated by the Hoehn and Yahr Scale and the unified Parkinson's disease rating scale (UPDRS). Results: After five weeks from prescription, patients taking pergolide mesilate showed significant improvement in the fatigue scale (from 5.1 ± 0.7 to 4.4 ± 0.55, p < 0.05, ) but patients taking bromocriptine did not (from 4.8 ± 0.9 to 4.7 ± 0.8). Conclusions: Our study suggested the possibility of functional correlation between fatigue and D1 receptor in patients with PD. [ABSTRACT FROM AUTHOR]

We analyzed the relationship between nafamostat mesilate (NM) level and activated coagulation time (ACT) as measured using an Actalyke MINI system vs. an ACTester system in patients with fulminant hepatitis undergoing continuous hemodiafiltration. The hemofilter was made with a polyacrylonitrile membrane, and NM was used as the anticoagulant. Significant correlation was found between the NM dose and the prehemofilter ACT measured by the Actalyke MINI system (r = 0.561, P = 0.0352, n = 14). However, no significant correlation was found between the NM dose and the prehemofilter ACT measured by the ACTester. Neither was a significant correlation found between the prehemofilter NM level and the prehemofilter ACT measured by either system. No significant correlation was found between the NM dose and the posthemofilter ACT measured by either system. The ACTester uses a test tube containing celite and a small amount of kaolin as a coagulation activator. The results of the present study suggest that the ACTester can adsorb NM and that this feature can affect ACT measurement. Considering this influence and the need to minimize the dose of NM in patients with fulminant hepatitis to avoid hemorrhagic tendencies, it is advisable to use the Actalyke MINI system.

Background:Autodigestion of the pancreas, secondary to the activation of digestive enzymes, is the pathogenetic mechanism of acute pancreatitis (AP). Aim:Clinical trials in which somatostatin (SS), octreotide (OCT) and gabexate mesilate (FOY) were used to treat patients with AP, were submitted to a meta-analytical evaluation. Five end-points were evaluated: early and overall mortality, patients with complications, complication rate, and patients who needed surgery. Results:In mild AP, no agent proved of value. In severe AP, both SS and OCT were beneficial in improving the overall mortality: the odds ratios (OR) were, respectively, 0.36 (95% CI: 0.20–0.64, P = 0.001) and 0.57 (95% CI: 0.35–0.88, P = 0.006). FOY had no effect on either early or overall mortality, but was effective in improving complication rate (OR = 0.70, 95% CI: 0.56–0.88, P = 0.02), number of patients with complications (OR = 0.61, 95% CI: 0.41–0.91, P = 0.01), and number of cases submitted to surgery (OR = 0.60, 95% CI: 0.39–0.92, P = 0.01). SS and OCT had no effect on these latter outcomes. Conclusions:Antisecretory agents, such as SS and OCT, are able to reduce mortality without affecting complications, whereas antiproteases, such as FOY, have no effect on mortality but do reduce complications. A trial exploring the efficacy of combining antisecretory agents with antiproteases would be of great benefit in patients with severe AP. [ABSTRACT FROM AUTHOR]

The use of extemporaneously prepared admixtures of drugs must be supported by documentation of their chemical stability. The objective was to assess the physical compatibility and the chemical stability of doxofylline with phentolamine mesilate in 0·9% sodium chloride or 5% dextrose injection for intravenous infusion. Total volumes of 20 and 1 mL of doxofylline solution and phentolamine mesilate solution, respectively, were added to 250 mL polyolefin bags containing 5% dextrose injection or 0·9% sodium chloride injection. Bags were stored for 24 h at 20-25 °C. Chemical compatibility was measures with high-performance liquid chromatography, and physical compatibility was determined visually. The samples were clear and colourless when viewed in normal fluorescent room light. The pH value and particulate content of the admixtures exhibited little change. The retentions of the initial concentration of doxofylline and phentolamine mesilate in the admixtures were within 97-105%. Doxofylline and phentolamine mesilate were stable in 5% dextrose injection or in 0·9% sodium chloride for up to 24 h at 20-25 °C. Doxofylline and phentolamine mesilate mixed in both 5% dextrose injection and 0·9% sodium chloride injection in 250 mL multilayer polyolefin bags at concentrations of 0·74 mg/mL and 36·9 μg/mL, respectively, were stable for up to 24 h at 20-25 °C. [ABSTRACT FROM AUTHOR]

A 59-year-old Japanese man developed septal panniculitis with eosinophilic infiltration in both forearms and the dorsum of the left hand after a gabexate mesilate intravenous drip infusion for acute pancreatitis through catheters implanted in these sites. Gabexate mesilate at a dose of 1000 mg per day had been given continuously for 8 days, and antibiotics were added by the same infusion route twice a day. All the infusion routes, however, became occluded one after the other. Reddish swelling first occurred at the left wrist 6 hours after occlusion of the infusion route, and, on both forearms, reddish swelling occurred about one week after the occlusion of each route. Patch testing revealed a +2 reaction to gabexate mesilate (10% pet) at days 3 and 7, and skin testing revealed indurated erythema to gabexate mesilate (0.1% aq) at days 2 and 3. The specimens biopsied from the positive skin testing reaction sites showed perivascular infiltrate and slight septal panniculitis. The inflammatory infiltrate consisted predominantly of lymphocytes with small numbers of eosinophils. Staining of the specimen biopsied from the right forearm lesion with anti-eosinophil cationic protein (ECP) antibodies (EG1 and EG2) showed deposition of eosinophil-derived granule proteins at the damaged septal connective tissues of the panniculitis. The panniculitis improved with topical steroid treatment. This case suggested that the concentration of infused gabexate mesilate may have been high enough to damage blood vessels and that gabexate mesilate may have leaked into the surrounding connective tissues, inducing allergic reactions and resulting in lesions.

Determines whether adverse effects of leukocytapheresis (LCAP) are related to mostat mesilate (NM) as an anticoagulant. Detection of anti-NM IgE in inflammatory bowel disease; Number of patients involved in the study; Relevance of NM as anticoagulant to the adverse effects of LCAP.

Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 +/- 5 (mean +/- SE) to 72 +/- 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.

We report on the experimental application of nafamostat mesilate (NM, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate, FUT), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow-fiber membrane lung at a blood flow rate of approximate 82 ml kg-1 min-1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml-1 in a priming lactated Ringer solution of 140 ml, and 200 U kg-1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200 s. To maintain the prolonged ACT, 8.0 +/- 1.7 mg kg-1 h-1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High-dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.

The adsorption of the anticoagulant nafamostat mesilate (FUT-175) by five different hemodialysis membranes was studied in vivo and in vitro. In vivo, FUT-175 was adsorbed strongly by a polyacrylonitrile (AN69) membrane and slightly by another polyacrylonitrile (J-PAN) membrane but not by Cuprophan (CU), hemophan (HE), or polymethylmethacrylate (PMMA) membranes during hemodialysis performed in 4 patients in whom FUT-175 was used as an anticoagulant. Only during hemodialysis using the AN69 membrane did FUT-175 not induce a significant prolongation of celite-activated coagulation time. In vitro studies showed that FUT-175 was adsorbed by the AN69, J-PAN, and PMMA membranes but not by the CU and HE membranes. Methylene blue, a dye that possesses a cationic portion in its chemical structure, stained AN69, J-PAN, and PMMA membranes. Since FUT-175 also possesses a cationic portion, we conclude that FUT-175 is adsorbed by negatively charged membranes via an ionic bond and is unsuited for use as an anticoagulant in hemodialysis using an AN69 membrane because of that membrane's marked capacity to adsorb FUT-175.

As an anticoagulant, we compared Nafamostat mesilate (FUT) to heparin in experimental direct hemoperfusion (DHP) and studied the efficacy of FUT in clinical plasma exchange (PE). In in vitro study, FUT (5 micrograms/ml) inhibited the activation of C4 more strongly than heparin (100 U/h), and larger dose of FUT (50 micrograms/ml) inhibited the activation of C3. Experimental DHP with FUT on jaundiced dogs was safely performed, but not with heparin. Clinical PE with FUT was safely performed and the hemostatic condition was not aggravated either during or after PE in patients with bleeding.

Leukocytapheresis (LCAP) is a therapeutic strategy for extra corporeal immunomodulation that has been used to treat several immunological disorders, including ulcerative colitis (UC), with encouraging results, inducing remission in steroid-resistant patients. However, we have experienced some complications during or after LCAP therapy. Common adverse effects include fever, chills, nausea, vomiting, and hypotension. One of the reasons for these adverse effects might be the use of nafamostat mesilate (NM) as an anticoagulant. In the present study, 75 patients with UC were divided into two groups, an NM group and a dalteparin sodium (DS) group. The clinical efficacy of these treatments, improvement after treatment, changes in leukocyte differential count, and adverse effects after LCAP therapy were then compared. The clinical efficacy, improvement after treatment, and changes in leukocyte classification were not significantly different between the two groups, while some adverse effects were observed in the NM group but not in the DS group. In conclusion, LCAP therapy is a useful therapy for patients with moderate to severe UC who fail to respond to glucocorticoid therapy, however, a safe anticoagulant should be used to avoid its related adverse effects. [ABSTRACT FROM AUTHOR]

Presents a study of the pharmacokinetics of nafamostat mesilate (NM) used as an anticoagulant in continuous hemodiafiltration with a polyacrylonitrile membrane used as the hemofilter. Risk of bleeding associated with heparin use; Diagnosis of multiple organ dysfunction syndrome; Correlation between the outlet NM concentration and catecholamine dose.

We studied nafamostat mesilate (NM) and interleukin (IL)-18 levels to determine whether the dose of NM is reduced during plasma exchange (PE) with continuous hemodiafiltration (CHDF) when the series-parallel circuit is used. The subjects of the current study included four patients with acute hepatic failure who underwent PE with CHDF. The four patients underwent a total 15 PE + CHDF procedures, and for each procedure, they were randomized to receive either a half-dose of NM or no NM in the CHDF circuit. Eight procedures were carried out with NM administration, and seven were carried out without NM administration. The dose of NM in the NM group was significantly higher than that in the non-NM group ( P = 0.040). No significant differences were observed between the two groups in the inlet NM concentration, the outlet NM concentration, or the rate of IL-18 removal. No statistical correlation was observed between the IL-18 level and the NM dose, the inlet NM concentration, or the outlet NM concentration. There was no blood access difficulty such as catheter failure or clotting of the filter. Thus, it might be possible to carry out PE and CHDF with the series-parallel method without administration of NM in the CHDF circuit. [ABSTRACT FROM AUTHOR]

A novel biodegradable aliphatic polycarbonate, poly(propylene carbonate maleate) (PPCMA) was synthesized by terpolymerization of carbon dioxide, propylene oxide, and maleic anhydride (MA), using a polymer supported bimetallic complex as catalyst. The utility of PPCMA to encapsulate and control the release of drug pazufloxacin mesilate (PZFX), via microcapsules, was investigated. PPCMA microcapsules containing PZFX were elaborated by solvent evaporation method based on the formation of double W/O/W emulsion. The manufacturing parameters such as the volume ratio of V(PPCMA) : V(PZFX), the concentration of stabilizer gelatin in outer aqueous phase played major roles on microcapsule characters, and were altered to optimize the process parameters. The PPCMA-PZFX microcapsules were obtained with smooth and spherical surface under optimum condition, the mean diameter of microcapsules was ∼ 2 μm, and the drug loading and drug encapsulation efficiency of the microcapsules were 22.9 ± 1.05% and 82.1 ± 2.03%, respectively. PZFX released from PPCMA microcapsules was found to reach 89.8 ± 2.89% after 36d in a pH 7.4 phosphate-buffered solution, and the release profile obeyed the Higuchi equation. The results suggest that the new polymer PPCMA provides an alternative to degradable matrix polymers for long-term sustained releasing drug delivery systems. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Background and objective: Oral mucositis is a major severe toxic side-effect of systemic chemotherapy and irradiation in patients with cancer. Various free radical scavengers have been shown to prevent chemotherapy-induced skin necrosis. The objective of this study was to determine the antioxidant activity of a bisbenzylisoquinoline alkaloidal compound (BIQAC) and a series of chemicals, including allopurinol, used clinically for the treatment of chemotherapy-induced mucositis. Methods: Allopurinol, melatonin, camostat mesilate, gabexate mesilate, hydroquinone and BIQAC were tested for their radical scavenging activities on four different radical species: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) cation radical (ABTS•+) using standard methods, and superoxide anion radical (O2−) and hydroxyl radical (OH•) using electron spin resonance. Results: Allopurinol had radical scavenging activity against O2− only. Melatonin had strong radical scavenging activity against ABTS•+, and weak activity against DPPH radical and OH•. Camostat mesilate had weak radical scavenging activity against OH•. Gabexate mesilate had no radical scavenging activity against any of these radicals. Hydroquinone had strong radical scavenging activity against DPPH radical and ABTS•+, and moderate activity against both O2− and OH•. BIQAC had moderate radical scavenging activity against DPPH radical, strong radical scavenging activity against ABTS•+ and O2−, and weak activity against OH•. Conclusion: The BIQAC had the most braod-spectrum radical scavenging activity, suggesting that it may be effective against chemotherapy-induced mucositis. These findings also suggest that this radical-scavenging activity screening method, against four kinds of radicals, may be useful for the screening of radical scavenging activity of new natural and synthetic chemicals. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to estimate and to characterize the actual patterns of ergot use and overuse in France using a drug reimbursement database. Methods We included all people covered by the French General Health Insurance System (GHIS) from the Provence-Alpes-Côte-d'Azur (PACA) and Corsica administrative areas who had at least one prescription of ergot between May 2010 and December 2011. All prescriptions of ergots, migraine prophylactic treatment, and psychotropic medications were extracted from the GHIS database. We defined occasional ergot users (<3 months of prescription) and regular ergot users (>3 months of prescription). Among regular ergot users, we identified overusers and nonoverusers. Results We included 4358 patients who had at least one prescription of ergots (oral ergotamine tartrate, dihydroergotamine mesilate nasal spray, intravenous dihydroergotamine mesilate). Among ergot overusers, a large majority of patients had ergotamine tartrate overuse. The proportion of ergotamine tartrate overusers is maximum after 55 years. Compared with regular users, overusers use more frequently a prophylactic treatment (93/165 [56.4%] versus 398/1057, OR = 2.15, P < .001), antidepressants (72/165 [43.6%] versus 326/1057 [30.8%] OR = 1.79, P < .001), benzodiazepines (111/165 [67.3%] versus 613/1057 [58.0%], OR = 1.50, P < .001), weak opioids (95/165 [57.6%] versus 463/1057 [43.8], OR = 1.77, P < .001) and strong opioids (13/165 [7.9%] versus 24/1057 [2.3%], OR = 3.86, P < .001). The coexistence of ergot consumption and triptan overuse, and the possibility of both triptan and ergot overuse was described; triptan overusers were more described in ergotamine overusers than in nonoverusers. Conclusions This work outlines a high prevalence of ergotamine tartrate overuse (11.1%). As ergotamine tartrate users are mostly aged more than 55 years, an evaluation of ergotamine cardiovascular risk profile is necessary in the elderly population. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is a useful diagnostic and therapeutic procedure; however, ERCP occasionally causes post-ERCP pancreatitis. The administration of gabexate mesilate has been reported to be effective for the prevention for post-ERCP pancreatitis when given during and after the procedure. The aim of the present study was to investigate the preventive effect of the novel protease inhibitor ulinastatin on post-ERCP pancreatitis. Methods: One hundred and thirty-nine patients who underwent the ERCP procedure were studied. These patients were randomly divided into three groups based on the agent and dose given during and following the ERCP procedure: gabexate mesilate (900 mg), high-dose ulinastatin (450 000 units) and low-dose ulinastatin (150 000 units). Serum amylase, interleukin (IL)-6 and IL-8 levels and plasma polymorphonuclear leukocyte elastase (PMN-E) activity were measured after ERCP. In addition, post-ERCP hyperamylasemia and post-ERCP pancreatitis were recorded. Results: There were no significant differences in serum amylase, IL-6 and IL-8 levels and PMN-E activity after ERCP procedure between the three groups. Post-ERCP pancreatitis was observed in two (4.3%), three (6.5%) and four (8.5%) cases in the gabexate mesilate, high-dose ulinastatin and low-dose ulinastatin groups, respectively. Multiple logistic regression analysis showed that the addition of endoscopic sphincterotomy during the ERCP procedure was the only significant risk factor for the development of post-ERCP hyperamylasemia and post-ERCP pancreatitis ( P = 0.03 and P = 0.04, respectively), but there was no significant difference in the occurrence of post-ERCP hyperamylasemia and post-ERCP pancreatitis between the three groups receiving different preventative treatments. Conclusion: The administration of low- and high-dose ulinastatin has similar effects to high-dose gabexate in the prevention of post-ERCP pancreatitis. [ABSTRACT FROM AUTHOR]

Dialysis‐related adverse reactions can be serious and difficult to predict. In our case, nafamostat mesylate (NM) was thought to be the cause of cardiopulmonary arrest (CPA) due to NM‐induced anaphylaxis but was not reflected in the allergy tests. Rare but life‐threatening drawbacks occur immediately after hemodialysis initiation. Despite proper hemodialysis (HD), cardiac arrest may occur immediately after the start of HD owing to the use of anticoagulants and dialysis membranes. It is essential to be aware of this unpredictable complication and apply strict observations. [ABSTRACT FROM AUTHOR]

A number of studies have shown that activated mast cells are involved in the pathogenesis of inflammatory and allergic diseases. Tryptase is one of the serine proteases that stored almost exclusively in the secretory granules of mast cells. It acts to induce microvascular leakage, the chemotaxis of inflammatory cells, and stimulates the release of inflammatory cytokines through the mitogen-activated protein kinase /activator protein-1 pathway and protease-activated receptor (PAR) nuclear factor- κB pathway. Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. The effect of anti-tryptase therapy on human inflammatory bowel disease and experimental colitis has been demonstrated. The result of a pilot study has revealed that systemic administration of a specific tryptase inhibitor is safe and there is evidence of activity in the treatment of ulcerative colitis. Recently, we found that nafamostat mesilate, which selectively inhibits tryptase activity at low concentration, could reduce intestinal inflammation in rats. In addition, nafamostat mesilate enema improved clinical and endoscopic findings in ulcerative colitis patients, resistant to conventional therapy such as corticosteroids and sulfasalazine/5-aminosalicylic acid. These studies suggest that anti-tryptase therapy may represent a new therapeutic strategy for human inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Nafamostat mesylate (NM) has been used to treat pancreatitis and disseminated intravascular coagulation during hemodialysis (HD). However, there have been some reports of adverse effects related to anaphylactic reactions. We present a case in which anaphylactic reactions caused by NM during preoperative HD caused repeated postponement of surgery for carpal tunnel syndrome. Symptoms including fever, shivering, chills, low blood pressure, tachycardia, nausea, and vomiting appeared during preoperative HD, and surgery was postponed thrice. Initially, the patient was misdiagnosed with sepsis because of elevated C-reactive protein and procalcitonin levels. However, since the symptoms appeared only when NM was administered and disappeared quickly after the administration of NM was terminated, the condition was diagnosed as anaphylactic reactions caused by NM. Therefore, it is essential to consider anaphylactic reactions caused by NM as differential diagnoses, when symptoms, such as fever, are observed during perioperative HD. [ABSTRACT FROM AUTHOR]

Liver failure due to ischemia-reperfusion injury, believed to be closely related to the generation of oxygen-free radicals, is a serious problem during liver surgery. Gabexate mesilate, a synthetic protease inhibitor, suppresses the extracellular release of oxygen-free radicals in the microvascular endothelium. To determine its effects on ischemia-reperfusion injury to the liver, we performed experiments with rats. We divided the animals into two ischemia-reperfusion groups: an experimental group, which underwent ischemic injury for 30 minutes, along with the infusion of gabexate mesilate, and a control group, which underwent injury only. Each group was then divided into four subgroups: ischemic injury only and 60-, 120-, and 180-minute reperfusion injury. The test parameters were tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in serum and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) in liver and lung tissues. The experimental group had a significantly higher liver SOD and catalase levels and a significantly lower level of liver and lung MDA than the control groups. TNFα levels in the experimental groups were significantly lower during the early phase, but a comparison of IL-6 levels between the two groups yielded no differences. Levels of lung catalase and SOD were not significantly different between the two groups. We concluded that protease inhibitor suppressed liver ischemia-reperfusion injury, and that it was due to an increase of antioxidant or suppression of oxygen-free radicals. The roles of TNFα and IL-6 in liver reperfusion injury were not clear, though TNFα might have had an effect during the early phase. With liver ischemia-reperfusion injury, the mechanism of lung involvement might be different from that of liver involvement. [ABSTRACT FROM AUTHOR]