Thalidomide modulates renal inflammation induced by brain death experimental model.

BACKGROUND: Brain death (BD) is characterized by a complex inflammatory response, resulting in dysfunction of potentially transplantable organs. This process is modulated by cytokines, which amplify graft immunogenicity. We have investigated the inflammatory response in an animal model of BD and analyzed the effects of thalidomide, a drug with powerful immunomodulatory properties. METHODS: BD was induced in male Lewis rats. We studied three groups: Control (sham-operated rats) (n = 6), BD (rats subjected to brain death) (n = 6) and BD + Thalid (BD rats treated with one dose of thalidomide (200 mg/Kg), administered by gavage) (n = 6). Six hours after BD, serum levels of urea and creatinine, as well as systemic and renal tissue protein levels of TNF-α and IL-6, were analyzed. We also determined the mRNA expression of ET-1, and macrophage infiltration by immunohistochemistry. RESULTS: BD induced a striking inflammatory status, demonstrated by a significant increase of plasma cytokines: TNF-α (2.8 ± 4.3 pg/mL [BD] vs. 9.4 ± 2.8 pg/mL [Control]), and IL-6 (6219.5 ± 1380.6 pg/mL [BD] vs. 1854.7 ± 822.6 pg/mL [Control]), and in the renal tissue: TNF-α (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.4 relative expression [Control]; p < 0.05), and IL-6 (4.0 ± 0.4 relative expression [BD] vs. 1.0 ± 0.3 relative expression [Control]; p < 0.05). Moreover, BD increased macrophages infiltration (2.47 ± 0.07 cells/field [BD] vs. 1.20 ± 0.05 cells/field [Control]; p < 0.05), and ET-1 gene expression (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.2 relative expression [Control]; p < 0.05). In addition, we have observed deterioration in renal function, characterized by an increase of urea (194.7 ± 25.0 mg/dL [BD] vs. 108.0 ± 14.2 mg/dL [Control]; p < 0.05) and creatinine (1.4 ± 0.04 mg/dL [BD] vs. 1.0 ± 0.07 mg/dL [Control]; p < 0.05) levels. Thalidomide administration significantly reduced plasma cytokines: TNF-α (5.1 ± 1.4 pg/mL [BD + Thalid] vs. BD; p < 0.05), and IL-6 (1056.5 ± 488.3 pg/mL [BD + Thalid] vs. BD; p < 0.05), as well as in the renal tissue: TNF-α (1.5 ± 0.2 relative expression [BD + Thalid] vs. BD; p < 0.05), and IL-6 (2.1 ± 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05). Thalidomide treatment also induced a significant decrease in the expression of ET-1 (1.4 ± 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05), and macrophages infiltration (1.17 ± 0.06 cells/field [BD + Thalid] vs. BD; p < 0.05). Also thalidomide prevented kidney function failure by reduced urea (148.3 ± 4.4 mg/dL [BD + Thalid] vs. BD; p < 0.05), and creatinine (1.1 ± 0.14 mg/dL [BD + Thalid] vs. BD; p < 0.05). CONCLUSIONS: The immunomodulatory properties of thalidomide were effective in decreasing systemic and local immunologic response, leading to diminished renal damage, as reflected in the decrease of urea and creatinine levels. These results suggest that use of thalidomide may represent a potential strategy for treating in BD kidney organ donors.

A Review of Simulators with Haptic Devices for Medical Training.

Medical procedures often involve the use of the tactile sense to manipulate organs or tissues by using special tools. Doctors require extensive preparation in order to perform them successfully; for example, research shows that a minimum of 750 operations are needed to acquire sufficient experience to perform medical procedures correctly. Haptic devices have become an important training alternative and they have been considered to improve medical training because they let users interact with virtual environments by adding the sense of touch to the simulation. Previous articles in the field state that haptic devices enhance the learning of surgeons compared to current training environments used in medical schools (corpses, animals, or synthetic skin and organs). Consequently, virtual environments use haptic devices to improve realism. The goal of this paper is to provide a state of the art review of recent medical simulators that use haptic devices. In particular we focus on stitching, palpation, dental procedures, endoscopy, laparoscopy, and orthopaedics. These simulators are reviewed and compared from the viewpoint of used technology, the number of degrees of freedom, degrees of force feedback, perceived realism, immersion, and feedback provided to the user. In the conclusion, several observations per area and suggestions for future work are provided.