The Role of HMGB1 in Traumatic Brain Injury-Bridging the Gap Between the Laboratory and Clinical Studies.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is amongst the leading causes of mortality and morbidity worldwide. However, several pharmacological strategies in the clinical setting remain unsuccessful. Mounting evidence implicates High Mobility Group Box protein 1 (HMGB1) as a unique alternative target following brain injury. Herein, we discuss current understanding of HMGB1 in TBI and obstacles to clinical translation. RECENT FINDINGS: HMGB1 plays a pivotal role as a 'master-switch' of neuro-inflammation following injury and in the regulation of neurogenesis during normal development. Animal models point towards the involvement of HMGB1 signalling in prolonged activation of glial cells and widespread neuronal death. Early experimental studies demonstrate positive effects of HMGB1 antagonism on both immunohistochemical and neuro-behavioural parameters following injury. Raised serum/CSF HMGB1 in humans is associated with poor outcomes post-TBI. HMGB1 is a promising therapeutic target post-TBI. However, further studies elucidating receptor, cell, isoform, and temporal effects are required prior to clinical translation.

Behavioral scientist meets the practicing physician.

The difficulty of integrating behavioral science into family practice programs is discussed by identifying (1) the problems arising from behavioral scientists, and (2) the problems arising from physicians. Some of the behavioral science issues discussed are miscommunications regarding the difficulty of understanding human behavior and empathy, and "sets" that affect diagnostic procedures and physician-patient interactions. Contributory issues, discussed which arise from physicians include the post-Flexnerian model of medical practice and the question of values in the physician role.

Studies on the pathogenesis of diet-induced dog gallstones.

Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.