Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis.

Tumor progression locus 2 (Tpl2) is a serine/threonine kinase in the mitogen-activated protein kinase signal transduction cascade known to regulate inflammatory pathways. Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. To address its role in skin carcinogenesis, Tpl2(-/-) or wild-type (WT) C57BL/6 mice were subjected to a two-stage dimethylbenzanthracene/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model. Tpl2(-/-) mice developed a significantly higher incidence of tumors (80%) than WT mice (17%), as well as a reduced tumor latency and a significantly higher number of total tumors (113 vs 6). Moreover, Tpl2(-/-) mice treated with TPA experienced significantly higher nuclear factor kappaB (NF-κB) activation, edema, infiltrating neutrophils and production of proinflammatory cytokines than did WT mice. We investigated the role of the p38, JNK, MEK and NF-κB signaling pathways both in vitro and in vivo in WT and Tpl2(-/-) mice by using inhibitors for each of these pathways. We confirmed that the proinflammatory effect in Tpl2(-/-) mice was due to heightened activity of the NF-κB pathway. These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation.

Efficacy of electrotactile vestibular substitution in patients with peripheral and central vestibular loss.

Vestibular dysfunction of either central or peripheral origin can significantly affect balance, posture, and gait. We conducted a pilot study to test the effectiveness of training with the BrainPort balance device in subjects with a balance dysfunction due to peripheral or central vestibular loss. The BrainPort balance device transmits information about the patient's head position via electrotactile stimulation of the tongue. Head position data is sensed by an accelerometer and displayed on the tongue as a pattern of stimulation. This pattern of stimulation moves forward, backward, and laterally on the tongue in direct response to head movements. Users of the device were trained to use this stimulation to adjust their position in order to maintain their balance. Twenty-eight subjects with peripheral or central vestibular loss were trained with the BrainPort balance device and tested using the following standardized quantitative measurements of the treatment effects: Computerized Dynamic Posturography (CDP) using the Sensory Organization Test (SOT), Dynamic Gait Index (DGI), Activities-specific Balance Confidence Scale (ABC), and Dizziness Handicap Inventory (DHI). All subjects had chronic balance problems and all but one had previously participated in vestibular rehabilitation therapy. The scores on the clinical tests upon entry into the study were compared to their scores following training with the BrainPort balance device. Our results exhibit consistent positive and statistically significant improvements in balance, posture and gait. These results exceed what could normally be achieved in three to five days of traditional balance training alone. Since this was not a controlled study, we are unable to distinguish the degree to which these improvements are attributable to training with the BrainPort balance device versus the balance exercises performed by all subjects as a part of the BrainPort training sessions. Nonetheless, after training with the BrainPort balance device, all subjects demonstrated significant improvements in performance beyond what might be expected from conventional vestibular rehabilitation therapy.

Efficacy of electrotactile vestibular substitution in patients with bilateral vestibular and central balance loss.

Patients with bilateral vestibular loss (BVL) of both central and peripheral origin experience multiple problems with balance and posture control, movement, and abnormal gait.Wicab, Inc. has developed the BrainPort balance device to transmit head position/orientation information normally provided by the vestibular system to the brain through a substitute sensory channel: electrotactile stimulation of the tongue. Head-orientation data (artificially sensed) serves as the input signal for the BrainPort balance device to control the movement of a small pattern of stimulation on the tongue that relates to head position in real-time. With training, the brain learns to appropriately interpret the information from the device and utilize it to function as it would with data from a normal-functioning natural sense. Ina total of 40 subjects trained with the BrainPort, 18 have been tested using standardized quantitative measurements of the treatment effects. A specialized set of exercises, testing, and training procedures has been developed that may serve as the course of intensive physical therapy with the BrainPort balance device. Our results demonstrate consistent positive and statistically significant balance rehabilitation effects independent of aging and etiology of balance deficit.

Characteristics of digital flexor tendon sheath fluid from clinically normal horses.

Physical, biochemical, and cytologic properties of synovial fluid from digital flexor tendon sheaths of clinically normal horses were investigated. Tendon sheath fluid was pale yellow, clear, and did not clot. Volume of fluid within a tendon sheath varied minimally, with a mean of 2.11 ml. Total erythrocyte counts were higher than values observed in normal equine joint fluid, whereas values for total leukocyte count (770 +/- 73 cells/mm3), viscosity (6.05 +/- 0.58 cs), and protein concentration (7.87 +/- 0.03 mg/ml) were similar to those in joint fluid. Large mononuclear cells were the predominant synovial fluid cell type. Mean hyaluronic acid concentration (0.74 +/- 0.02 mg/ml) and mucinous precipitate quality were lower than values in joint fluid.