Case Report: Treatment of a Severe Puff Adder Snakebite Without Antivenom Administration.

Antivenoms are the treatment of choice for managing lethal snakebites. However, antivenoms may not be available in instances where non-native vipers are kept in captivity. We report a case of a puff adder (Bitis arietans) bite treated without antivenom. A 23-year-old man was bitten on his left hand by a puff adder that he illegally kept in his house. The swelling spread rapidly to the upper arm and there was a risk of bleeding, suggesting the need for antivenom administration, but this could not be acquired because of lack of stock. We initiated fluid resuscitation and administered recombinant thrombomodulin (rTM) to prevent venom-induced consumption coagulopathy. In addition, hyperbaric oxygen (HBO) treatment was also performed to reduce local swelling. The patient recovered without complications after the multidisciplinary treatment. Further studies are needed to prove the safety and efficacy of rTM administration and HBO therapy as an adjunct or alternative therapy with antiserum for fatal snakebite.

Efficacy of Recombinant Human-Soluble Thrombomodulin for Severe Acute Pancreatitis in a Rat Experimental Model.

OBJECTIVES: Early death in severe acute pancreatitis (SAP) is caused by pancreatic necrosis and multiple-organ failure due to microcirculation disorder. The aim of this study was to prove that recombinant human-soluble thrombomodulin (rTM) has therapeutic effects on SAP by preventing pancreatic necrosis and organ failure. METHODS: Male Wister rats were used. Cerulein was administered intraperitoneally 4 times every 1 hour, and lipopolysaccharide was administered intraperitoneally 3 hours after. One hour after administration of lipopolysaccharide, rTM was injected intravenously. Rats were observed for 24 hours after starting the experiment, and the survival rate was evaluated. All surviving rats were killed, and the blood sample, liver, and pancreas were excised. Serum amylase, aspartate aminotransferase, alanine aminotransferase, and high mobility group box 1 were measured, and the liver and pancreas were examined histologically. For the evaluation of microcirculation, von Willebrand factor staining was performed. RESULTS: Serum amylase, aspartate aminotransferase, and alanine aminotransferase were significantly decreased. The survival rate was significantly improved to 100%. Moreover, serum high mobility group box 1 was decreased. Liver injury and pancreatic necrosis became less severe, and microcirculation was preserved histologically. CONCLUSIONS: Early administration of rTM prevents organ failure by maintenance of microcirculation and improves prognoses of SAP.

Emerging therapies for the treatment of sepsis.

PURPOSE OF REVIEW: Sepsis affects patients of all ages with multiple comorbidities and underlying diagnoses, and is the result of infection by many potential pathogens infecting various organs or sites. Many molecules have been clinically tested in recent years for their potential immunomodulatory effects, but have been shown to have no beneficial effects on outcomes in heterogeneous populations of patients with sepsis. There are, therefore, no specific antisepsis therapies and mortality and morbidity rates remain high despite improved overall management of these patients. This review covers promising agents currently used in clinical trials. RECENT FINDINGS: There are several candidates currently undergoing early and later phase of clinical testing, including thrombomodulin, alkaline phosphatase, interferon-beta, and selepressin. Other approaches including immunoglobulins, extracorporeal therapies, and pharmaconutrients will also be discussed. SUMMARY: Despite multiple trials of potential therapies for sepsis, no strategies have yet been persistently shown to have beneficial effects on outcomes. The main reason for the disappointing results is that patient populations in these studies have been too heterogeneous. Selecting patients on the basis of general symptoms is not enough. Rather patients should be selected according to the likely action of the drug in question. To achieve this, improved biomarkers of sepsis and of the immune response are needed and the activities of the individual agents need to be carefully characterized. New candidates are being developed and the results of ongoing and recent clinical trials of immunomodulatory therapies are eagerly awaited as new therapies for sepsis are urgently needed.

Thrombomodulin improves rat survival after extensive hepatectomy.

BACKGROUND: Recombinant human soluble thrombomodulin (rTM) protects against disseminated intravascular coagulopathy by inhibiting coagulation, inflammation, and apoptosis. This study tests the hypothesis that rTM is hepatoprotective after extensive hepatectomy (Hx) and investigates the mechanisms underlying this effect. MATERIALS AND METHODS: Experiment 1: rats (15 per group) were injected with rTM (1.0 or 2.0 mg/kg) or saline just before 95% Hx and their 7-d survival assessed. Experiment 2: rats were assigned to either a treated (2.0 mg/kg rTM just before Hx) or control group (n = 5 per group). Five rats per group were euthanized immediately after surgery, and at 1, 3, 6, 12, and 24 h postoperatively; serum and liver remnant samples were collected for biochemical and histologic analysis, as well as reverse-transcription polymerase chain reaction and Western blotting. RESULTS: All saline-injected rats died within 52 h of Hx, whereas injection of 2.0 mg/kg rTM prolonged survival (P = 0.003). rTM increased the number of Ki67-positive cells and reduced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. The number of myeloperoxidase-positive cells and the expression of high-mobility group box 1 protein did not differ. Reverse-transcription polymerase chain reaction revealed that rTM significantly enhanced protease-activated receptor-1 and sphingosine kinase 1 messenger RNA expression and significantly reduced plasminogen activator inhibitor-1 and Bax messenger RNA expression. Immunohistochemistry and Western blotting demonstrated that protease-activated receptor-1 expression 24 h after Hx was significantly higher in rTM-treated than in control rats. CONCLUSIONS: rTM may improve survival after extensive Hx by inhibiting apoptosis and promoting liver regeneration.

Severe drug-induced interstitial lung disease successfully treated with corticosteroid plus recombinant human soluble thrombomodulin.

There is no established therapeutic option for corticosteroid (CS) refractory drug-induced interstitial lung disease (DILD). We report a case of CS refractory severe DILD successfully treated with recombinant human soluble thrombomodulin (rhTM). A 64-year-old Japanese man was admitted with symptoms of fever, dry cough and dyspnoea. A chest radiograph showed bilateral infiltrations. DILD from Nijutsutou, a Chinese medicine, was suspected based on a history of similar interstitial lung disease after its administration 4 years prior and a positive drug-induced lymphocyte stimulation test. Nijutsutou was promptly discontinued and high doses of CS administered, but the patient's bilateral infiltrations remained unimproved. Since coagulation tests also indicated a rapid aggravation of coagulopathy, rhTM was added to the CS therapy. The patient's lung infiltration ameliorated and plasma levels of D-dimer and high morbidity group box 1 (HMGB1) decreased. rhTM may be an alternative agent for CS refractory DILD. Further study is necessary to confirm this.