Protein kinase C agonist and antagonist effects in normal human epidermal keratinocytes

Abstract Several lines of evidence implicate protein kinase C (PKC) in the development of basal cell and squamous cell carcinomas, tumors which originate from epidermal keratinocytes. To examine PKC in a model relevant to human skin, we exposed normal human epidermal keratinocytes (NHEK) in serum-free media to a variety of PKC agonists and antagonists. NHEK PKC activity increased up to 10-fold within the 1st hour of exposure to tetradecanoyl phorbol acetate (TPA), and gradually returned to control values within 72 h. TPA-induced PKC activity was enhanced by pretreatment of cultures with protein and RNA synthesis inhibitors. TPA-induced growth arrest and differentiation was antagonized by staurosporine. Down-regulation by bryostatin pretreatment blocked TPA-stimulated differentiation. Our overall conclusion is that activation of PKC in cultured human keratinocytes is required for differentiation. These results are crucial to the analysis of compounds suspected of promoting or inhibiting epidermal tumors.     

The role of arthroscopy in the problem total knee replacement

Fourteen patients were retrospectively reviewed to examine the role of arthroscopy in the diagnosis and treatment of the problem total knee arthroplasty (TKA), and to define parameters for indications, techniques, and results. All patients had undergone a previous TKA, and postoperatively had problems with pain and/or range of motion. Routine evaluation failed to reveal sepsis or aseptic loosening. Arthroscopy was used to evaluate and treat certain specific conditions. The arthroscope was successful in removing loose bodies, correcting patella subluxation with an arthroscopic lateral release, excising a symptomatic pseudomeniscus, and releasing intraarticular adhesions to improve motion and relieve pain. The postoperative knee score improved 73%. Arthroscopy is a valuable tool to evaluate a painful TKA, and can be used to treat certain conditions that would otherwise require an arthrotomy. The rehabilitation time is easier on the patient and much quicker. Arthroscopy of a TKA does not compromise any future procedures. However, it remains a technically demanding procedure whose indications and expectations are still being defined.     

A randomized, blinded trial of uncooked cornstarch to diminish nocturnal hypoglycemia at Diabetes Camp

Objective: To determine if uncooked cornstarch, as part of the evening snack, can avert nocturnal hypoglycemia in type 1 diabetes. Research Design and Methods: Fifty-one campers and counselors at the American Diabetes Association Camp in San Bernardino, CA were randomly assigned to receive 5 g of uncooked cornstarch as part of the 21:00 evening snack vs. a standard snack of equivalent carbohydrate content. Each snack was given for five nights and the participants and medical personnel were blinded as to assignment. Midnight and 07:00 finger stick blood glucose levels were compared with values <60 mg/dl defined as hypoglycemia and values >250 mg/dl defined as hyperglycemia. Results: There were 218 midnight and 222 07:00 values for comparison. There were six episodes of hypoglycemia at midnight and nine episodes of hypoglycemia at 07:00 for the cornstarch snack nights vs. 30 hypoglycemia episodes at midnight and 21 at 07:00 for the standard snack nights (P < 0.001 and < 0.05, respectively). There was no difference in the number of hyperglycemic events at midnight or 07:00 for the cornstarch vs. standard snack nights. At midnight, 12% of campers had hypoglycemia after the cornstarch snack vs. 46% after the standard snack (P < 0.001), and at 07:00, 16% had hypoglycemia after cornstarch vs. 26% after the standard snack (P = 0.327). Conclusions: These data suggest that uncooked cornstarch, as part of the evening snack, can diminish the nighttime and morning hypoglycemia associated with type 1 diabetes, without causing hyperglycemia.