Efficacy of the Novel Medical Adhesive, MAR-VIVO-107, in an Acute Porcine Liver Resection Model.

BACKGROUND: Despite modern surgical techniques, insufficient hemostasis after liver trauma is still a major cause of morbidity and mortality after injury. Therefore, efficient hemostatic agents are indicated. In this study, we evaluated the hemostatic efficacy of a novel synthetic wound adhesive (MAR-VIVO-107) based on polyurethane/polyurea, compared with a widely used fibrin adhesive (Tisseel). MATERIALS AND METHODS: Twelve German Landrace pigs were randomly assigned to 2 groups. The animals were operated under sterile conditions. A midline laparotomy was performed and the left liver lobe was isolated and resected, using a surgical scissor, in order to induce hepatic trauma. MAR-VIVO-107 or Tisseel was applied to the resected area. The animals were monitored for 60 minutes; thereafter, they were sacrificed under anesthesia. Blood and tissue samples were collected pre- and postresection for biochemical and hematological analyses. RESULTS: MAR-VIVO-107 versus Tisseel (mean ± SD, P value)-postsurgical survival rate was 100% in both groups. Bleeding time was significantly higher in Tisseel compared with MAR-VIVO-107 (10.3 ± 5.0 vs 3.7 ± 1.5 minutes, P = .0124). In trend, blood loss was less in the MAR-VIVO-107 group (54.3 ± 34.9 vs 105.5 ± 65.8 g, P = .222). Aspartate transaminase levels were significantly lower in the MAR-VIVO-107 group when compared with the Tisseel group (39.0 ± 10.0 vs 72.4 ± 23.4 U/L, P = .0459). CONCLUSION: The efficacy of MAR-VIVO-107 and comparable performance to the gold standard fibrin have been shown under pre-clinical conditions. MAR-VIVO-107 permits hemorrhage control within seconds, even in wet environment.

2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.

A series of 2-aryl pyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Multiple compounds showed highly potent TRPV1 antagonism toward capsaicin comparable to previous lead 7. Among them, compound 9 demonstrated anti-allodynia in a mouse neuropathic pain model and blocked capsaicin-induced hypothermia in a dose-dependent manner. Docking analysis of 9 with our hTRPV1 homology model provided insight into its specific binding mode.

Defining body-weight reduction as a humane endpoint: a critical appraisal.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct animal experiments in multiple research facilities, and assessed whether 20% body-weight reduction is a valid humane endpoint criterion in rodents. In most experiments (restraint stress, distinct models for epilepsy, pancreatic resection, liver resection, caloric restrictive feeding and a mouse model for Dravet syndrome) the animals lost less than 20% of their original body weight. In a glioma model, a fast deterioration in body weight of less than 20% was observed as a reliable predictor for clinical deterioration. In contrast, after induction of chronic diabetes or acute colitis some animals lost more than 20% of their body weight without exhibiting major signs of distress. In these two animal models an exclusive application of the 20% weight loss criterion for euthanasia might therefore result in an unnecessary loss of animals. However, we also confirmed that this criterion can be a valid parameter for defining the humane endpoint in other animal models, especially when it is combined with additional criteria for evaluating distress. In conclusion, our findings strongly suggest that experiment and model specific considerations are necessary for the rational integration of the parameter 'weight loss' in severity assessment schemes and humane endpoint criteria. A flexible implementation tailored to the experiment or intervention by scientists and authorities is therefore highly recommended.