Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc

While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short- (hours) and long-term (days) and evaluated the IVDs\u27 response. Activating TRPV4 with the agonist GSK101 resulted in a C

Pleiotropic effects of simvastatin and losartan in preclinical models of post-traumatic elbow contracture

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: a

Increasing dorsal tilt in distal radius fractures does not increase median nerve strain

Although extensive research shows an association between distal radius fractures and the development of median nerve related pathologies such as carpal tunnel syndrome, none directly track how the resulting angular deformity relates to likelihood of development of median nerve pathology. Methods: Median nerve strain was measured with a custom-built system using a camera, optical markers, and a proprietary segmentation algorithm. After initial validation of the system in a cadaver model, our system was used to assess strain in 10 cadaver arms with a simulated distal radius fracture and increasing dorsal angulation. The measured strain at each angle was then analyzed using a linear regression model. Results: The linear regression model in the validation experiment demonstrated a regression coefficient of 1.00067 ( Conclusions: Increases in median nerve strain at the wrist are negligible with increasing dorsal tilt in a distal radius fracture model. It is therefore likely that other factors, such as increased pressure within the carpal tunnel, are the primary cause of median neuropathy in distal radius malunions. Therefore, correction of dorsal tilt may not be required to improve neurologic symptoms

Hematology-oncology pharmacists: We hear you, we see you, we support you

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175550/1/jac51707.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175550/2/jac51707_am.pd