Kynurenic acid and its analogue SZR-72 ameliorate the severity of experimental acute necrotizing pancreatitis

The pathophysiology of acute pancreatitis (AP) is not well understood, and the disease does not have specific therapy. Tryptophan metabolite L-kynurenic acid (KYNA) and its synthetic analogue SZR-72 are antagonists of the N-methyl-D-aspartate receptor (NMDAR) and have immune modulatory roles in several inflammatory diseases. Our aims were to investigate the effects of KYNA and SZR-72 on experimental AP and to reveal their possible mode of action. AP was induced by intraperitoneal (i.p.) injection of L-ornithine-HCl (LO) in SPRD rats. Animals were pretreated with 75-300 mg/kg KYNA or SZR-72. Control animals were injected with physiological saline instead of LO, KYNA and/or SZR-72. Laboratory and histological parameters, as well as pancreatic and systemic circulation were measured to evaluate AP severity. Pancreatic heat shock protein-72 and IL-1β were measured by western blot and ELISA, respectively. Pancreatic expression of NMDAR1 was investigated by RT-PCR and immunohistochemistry. Viability of isolated pancreatic acinar cells in response to LO, KYNA, SZR-72 and/or NMDA administration was assessed by propidium-iodide assay. The effects of LO and/or SZR-72 on neutrophil granulocyte function was also studied. Almost all investigated laboratory and histological parameters of AP were significantly reduced by administration of 300 mg/kg KYNA or SZR-72, whereas the 150 mg/kg or 75 mg/kg doses were less or not effective, respectively. The decreased pancreatic microcirculation was also improved in the AP groups treated with 300 mg/kg KYNA or SZR-72. Interestingly, pancreatic heat shock protein-72 expression was significantly increased by administration of SZR-72, KYNA and/or LO. mRNA and protein expression of NMDAR1 was detected in pancreatic tissue. LO treatment caused acinar cell toxicity which was reversed by 250 µM KYNA or SZR-72. Treatment of acini with NMDA (25, 250, 2000 µM) did not influence the effects of KYNA or SZR-72. Moreover, SZR-72 reduced LO-induced H(2)O(2) production of neutrophil granulocytes. KYNA and SZR-72 have dose-dependent protective effects on LO-induced AP or acinar toxicity which seem to be independent of pancreatic NMDA receptors. Furthermore, SZR-72 treatment suppressed AP-induced activation of neutrophil granulocytes. This study suggests that administration of KYNA and its derivative could be beneficial in AP

A new modular testing system for biomechanical evaluation of tibial intramedullary fixation devices

This biomechanical study was performed to evaluate a new modular, tibial testing system developed for analysis of tibial nails and their locking screws. A new testing system, consisting of five modules, was designed to simulate a tibia. For this study one module was removed to simulate a 55-mm distal tibial defect inducing maximum loading on the distal portion of the implant and locking bolts. The tibial load offsets were 23 mm proximally and 10 mm distally medial to the centreline of the tibial shaft to simulate the location of the expected resultant load during the peak loading and inversion torque on the ankle during the gait cycle. Four solid tibial nails (STN®, Stryker-Howmedica-Osteonics, Kiel, Germany) were tested to static failure and 15 nails were tested dynamically. Our results showed that the solid tibial nails fractured in the testing device in the same manner and location as they do in clinical series. Evaluation of the results showed the mean fatigue limit of the STN to be 1.4 kN for 500 000 cycles with a standard deviation (S.D.) of 0.33 kN. This biomechanical study establishes a standard technique for the biomechanical testing of tibial nails, in a clinically relevant manner, avoiding the inconsistency of cadaver bone tests. As it is a standardised test set-up this new modular testing system could serve as a standard by which small diameter tibial nails and other devices could be evaluated and compared with other systems currently in use

Physeal injuries of the distal tibia: long-term results in 376 patients

The aim of this study was to evaluate our treatment of distal tibial physeal injuries retrospectively and explain the relationship between the trauma mechanism, the radiographic injury pattern, the subsequent therapy and the functional outcome, as well as to further deduce and verify prognostic criteria. At the Department of Trauma Surgery, Vienna Medical University, 419 children and adolescent patients with physeal injuries of the distal tibia were treated from 1993 to 2007, of these 376 were included in our study and evaluated retrospectively. Seventy-seven displaced physeal fractures of the distal tibia were reconstructed anatomically by open or closed reduction and produced 95% excellent results. A perfect anatomical reduction, if necessary by open means, should be achieved to prevent a bone bridge with subsequent epiphysiodesis and post-traumatic deformities due to growth inhibition and/or retardation

Fractures of the head and neck of the femur in children: an outcome study

Fractures of the head and neck of the femur in children are very rare, occurring only after a high-velocity trauma, e.g. a fall from a height. This analysis shows the clinical course of traumatic femoral head and neck fractures in paediatric patients. Predisposing factors for poor outcome or fracture complications, such as non-union or femoral head necrosis, are described. Between 1993 and 2006, 16 paediatric patients with proximal femoral fractures were treated at the Level One Trauma Centre of the Medical University of Vienna. The minimum follow-up was two years. Inclusion criteria were age less then 16 years, intact growth plate and a proximal femoral fracture according to the classification by Delbet and Colonna. Exclusion criteria were pathological fractures or fractures of the subtrochanteric region (6/16). Ten patients met the inclusion criteria. Two patients were lost to follow-up. Therefore eight patients were included in the study. All patients except one were operated upon within 48 h after the injury (“primary”) and healed without further complications. A single case was managed by “secondary” surgical treatment, two weeks after the initial trauma resulting in femoral head necrosis that healed without any subjective complaints. This case series confirms the importance of early surgical fixation of proximal femoral fractures in paediatric patients. An operative intervention later then 48 h after the initial trauma may increase the risk of complications such as femoral head necrosis, particularly in Delbet type I fractures (traumatic slipped capital femoral epiphysis)