Human SMOOTHENED inhibits human immunodeficiency virus type 1 infection.

Human SMOOTHENED (SMO) was identified by expression cloning as a new host factor that inhibits HIV-1 infection. Forced expression of SMO inhibited HIV-1 replication and infection with a single-round lentiviral vector, but not infection with a murine leukemia virus-based retroviral vector in human MT-4 T cells. Quantitative PCR analyses revealed that stable expression of SMO impaired formation of the integrated form of lentiviral DNA, but did not interrupt reverse transcription. This inhibition was evident in MT-4 and HUT102 human T cell lines expressing low levels of SMO mRNA, but not in SupT1 or Jurkat T cell lines expressing higher levels of SMO mRNA. Depletion of SMO mRNA in Jurkat cells facilitated HIV-1 vector infection, suggesting that endogenous SMO plays a role in limiting lentiviral infection. These results suggest that SMO inhibits HIV-1 replication after completion of reverse transcription but before integration.

Development of a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of osteoporosis.

Bisphosphonates are widely used for the treatment and prevention of bone diseases, including Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis. In this study, we developed a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of bone diseases. The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1.9 and 0.3 µg/cm(2) per hour, respectively. The bioavailability (BA) of alendronate in rats was approximately 8.3% after the application of alendronate patch and approximately 1.7% after oral administration. These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases. The plasma calcium level was effectively reduced after application of the alendronate patch in 1α-hydroxyvitamin D(3) -induced hypercalcemia model rats. The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis. Modest alendronate-induced erythema of rat skin was observed after application of the alendronate patch. Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate-induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate. These findings indicate that our novel transdermal delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases.

Carbon dioxide insufflation is useful for obtaining clear images of the bile duct during peroral cholangioscopy (with video).

BACKGROUND: Peroral cholangioscopy (POCS) is useful for the diagnosis of various bile duct lesions. However, it is often difficult to obtain clear images because of bile or biliary sludge in the bile duct, even after vigorous irrigation of the bile duct with saline solution. Therefore, this study investigated whether inflation with carbon dioxide (CO(2)) yields clearer images of the bile duct than conventional saline solution irrigation during POCS. OBJECTIVE: To evaluate the clinical utility and safety of CO(2) insufflation into the bile duct to obtain clear images in POCS observations by comparing this method with conventional saline solution irrigation. SETTING: A single center. DESIGN: Case-control study. PATIENTS: Nineteen patients with suspected biliary diseases. INTERVENTIONS: CO(2) insufflation into the bile duct during POCS. MAIN OUTCOME MEASUREMENTS: The quality and safety of this method. RESULT: The quality of the images of the bile duct lumen with CO(2) insufflation (10 patients) was significantly superior to those with saline solution irrigation (9 patients) in both clarity (P < .05) and color (P < .05). In particular, extremely clear images could be obtained from the middle part of common bile duct to the right and left hepatic duct. No serious POCS-related complications occurred. There was no significant change in the venous partial pressure of the CO(2) level during the procedure. LIMITATIONS: The number of patients examined was small. CONCLUSIONS: CO(2) insufflation is useful for obtaining clear images of the bile duct during POCS, which makes it possible to determine the qualitative diagnosis and the extent of various bile duct lesions.