Investigation of the utility of the 1.1B4 cell as a model human beta cell line for study of persistent enteroviral infection.

The generation of a human pancreatic beta cell line which reproduces the responses seen in primary beta cells, but is amenable to propagation in culture, has long been an important goal in diabetes research. This is particularly true for studies focussing on the role of enteroviral infection as a potential cause of beta-cell autoimmunity in type 1 diabetes. In the present work we made use of a clonal beta cell line (1.

Knee joint loading during lineman-specific movements in American football players.

Linemen are at high risk for knee cartilage injuries and osteoarthritis. High-intensity movements from squatting positions (eg, 3-point stance) may produce high joint loads, increasing the risk for cartilage damage. We hypothesized that knee moments and joint reaction forces during lineman-specific activities would be greater than during walking or jogging.

Towards the conservation of endangered avian species: a recombinant West Nile Virus vaccine results in increased humoral and cellular immune responses in Japanese Quail (Coturnix japonica).

West Nile Virus (WNV) arrived in North America in 1999 and is now endemic. Many families of birds, especially corvids, are highly susceptible to WNV and infection often results in fatality. Avian species susceptible to WNV infection also include endangered species, such as the Greater Sage-Grouse (Centrocercus uropbasianuts) and the Eastern Loggerhead Shrike (Lanius ludovicianus migrans).

A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients.

The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug.

A novel ENU-induced mutation, peewee, causes dwarfism in the mouse.

We identified a novel fertile autosomal recessive mutation called peewee that results in dwarfing, in a region-specific ENU-induced mutagenesis. These mice at litter size were smaller those of other strains. Histological analysis revealed that the major organs appear normal, but abnormalities in cellular proliferation were observed in bone, liver, and testis.

Long-term benefits of darifenacin treatment for patient quality of life: results from a 2-year extension study.

Background And Aims: Overactive bladder (OAB), a chronic condition requiring long-term management, is associated with substantial impact on health-related quality of life (HRQoL). The short-term benefits of antimuscarinic drug treatment are well known. Here we investigate the impact on HRQoL of long-term treatment with the M(3)-selective muscarinic receptor antagonist darifenacin over 2 years.

Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Purpose: We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Materials And Methods: Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo.

Results: Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.

Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial.

Purpose: We evaluated sildenafil for erectile dysfunction and lower urinary tract symptoms in men with the 2 conditions.

Materials And Methods: This was a 12-week, double-blind, placebo controlled study of sildenafil in men 45 years or older who scored 25 or less on the erectile function domain of the International Index of Erectile Function and 12 or greater on the International Prostate Symptom Score. Men with confirmed or suspected prostate malignancy, or prostate specific antigen 10 ng/ml or more were excluded.

Dutasteride improves objective and subjective disease measures in men with benign prostatic hyperplasia and modest or severe prostate enlargement.

Purpose: We determined whether the effect of dutasteride for benign prostatic hyperplasia is influenced by baseline prostate volume using data from 3 phase III clinical trials.

Materials And Methods: Patients randomized to dutasteride or placebo in the double-blind portion of the phase III studies were eligible to receive 0.5 mg dutasteride daily in a 2-year open label extension in dutasteride/dutasteride and placebo/dutasteride groups.

Role of quality of life in men with metastatic hormone-refractory prostate cancer: how does atrasentan influence quality of life?

Objective: Progression of hormone-refractory prostate cancer (HRPC) is associated with skeletal complications and bone pain, which contribute to deterioration in quality of life (QOL). The effects of new HRPC therapies on patients' QOL need to be studied. Patient-based assessments that help quantify the risk-benefit profile of HRPC therapies are warranted.

Sustained efficacy and safety of vardenafil for treatment of erectile dysfunction: a randomized, double-blind, placebo-controlled study.

Objective: To evaluate the reliability, efficacy, and safety of vardenafil, 10 mg, for patients with erectile dysfunction.

Patients And Methods: Vardenafil-naive patients completed a 4-week treatment-free run-in phase and a 1-week single-dose vardenafil (10 mg) open-label challenge phase. Responders to vardenafil in the challenge phase were randomized to 12 weeks of double-blind, fixed-dose treatment with vardenafil at 10 mg or placebo.

Tadalafil improved erectile function at twenty-four and thirty-six hours after dosing in men with erectile dysfunction: US trial.

In a previous study assessing tadalafil for the treatment of erectile dysfunction (ED), tadalafil 20 mg was shown to improve erectile function for up to 36 hours vs placebo. This study sought to demonstrate the effectiveness of both 10- and 20-mg tadalafil vs placebo at 2 prespecified assigned times of 24 and 36 hours postdosing. This double-blind, placebo-controlled, parallel-group study randomized 483 men with ED into 6 groups according to a combination of treatment (placebo, tadalafil 10 or 20 mg) and assigned time (24 or 36 hours) for intercourse attempts.

Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups.

Objectives: To assess whether vardenafil would improve erectile function irrespective of etiology, baseline severity, or patient age. The consistency of the response over time was also evaluated.

Methods: A multicenter, randomized, double-blind, placebo-controlled at-home study of vardenafil treatment (5, 10, and 20 mg) was performed.

Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study.

Objective: This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes.

Research Design And Methods: In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks. Efficacy responses were assessed by International Index of Erectile Function domain scores, rates of vaginal penetration and successful intercourse, and a global assessment question (GAQ) about erection improvement during the previous 4 weeks.

Efficacy and safety of sildenafil citrate (Viagra) in black and Hispanic American men.

The objective of this study was to assess the efficacy and safety of sildenafil citrate (Viagra) in black American and Hispanic American men with erectile dysfunction (ED) of broad-spectrum etiology. A total of 246 black American and 197 Hispanic American men were randomized to sildenafil (50 mg, adjustable to 25 mg or 100 mg, depending on efficacy and tolerability; n = 124 and n = 99, respectively) or matching placebo (n = 122 and n = 98, respectively). After 6 weeks, patients were given the option of switching to the other blinded treatment for the following 6 weeks.

Vardenafil.

Vardenafil hydrochloride is a potent and highly selective inhibitor of phosphodiesterase Type 5 that increases blood flow to the penis during sexual stimulation and helps restore the ability to achieve and sustain an erection in men with erectile dysfunction. Vardenafil was developed specifically to be an effective and safe oral medication for the treatment of erectile dysfunction, with potential advances over existing therapies. This review summarises key findings during the rapid and aggressive development of this compound, from in vitro assays to Phase III trials with both broad and special populations.