Development of a long-acting insulin analog using albumin fusion technology.

The primary therapeutic goal for the treatment of diabetes is maintenance of a long-term, near-normoglycemic condition and prevention of the onset or progression of the complications associated with the disease. Although several analogs of human insulin have been developed, the currently prescribed long-acting insulin analogs do not provide a stable basal glycemia for more than a few hours. Here, we report the development of Albulin, a long-acting insulin analog obtained by direct gene fusion of a single-chain human insulin to human serum albumin.

Serotype distribution and antimicrobial resistance patterns of nasopharyngeal and invasive Streptococcus pneumoniae isolates in Hong Kong children.

A study was conducted to determine the vaccine coverage of prevalent carriage and invasive pneumococci from children aged less than 6 years in Hong Kong. A total of 383 nasopharyngeal carriage isolates and 88 invasive isolates from diverse sources were serotyped and their antimicrobial susceptibilities determined. The most common carriage serotypes were the same as the invasive isolates (6B, 14, 19F and 23F), although the rank order of specific serotypes was different.

The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins.

Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K.

Clinical trial of an educational intervention to achieve recommended cholesterol levels in patients with coronary artery disease.

Background: Despite national efforts to improve cholesterol management for patients with coronary artery disease, many patients are not reaching recommended cholesterol target levels. We sought to determine whether a nurse-based educational intervention, designed to educate patients with confirmed coronary artery disease about personal low-density lipoprotein (LDL) cholesterol target levels and encourage partnership with physicians, could increase adherence with National Cholesterol Education Program target levels (LDL cholesterol level < or =100 mg/dL).

Methods: Patients hospitalized with confirmed coronary artery disease were randomized to undergo a nurse-based educational intervention (375 patients) or usual care (381 patients) for a 12-month period after hospitalization.

Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status.

The mammalian target of rapamycin (mTOR) is a key regulator of protein translation. Signaling via mTOR is increased by growth factors but decreased during nutrient deprivation. Previous studies have identified Ser2448 as a nutrient-regulated phosphorylation site located in the mTOR catalytic domain, insulin stimulates Ser2448 phosphorylation via protein kinase B (PKB), while Ser2448 phosphorylation is attenuated with amino acid starvation.

Worsening renal function: what is a clinically meaningful change in creatinine during hospitalization with heart failure?

Introduction: Worsening renal function during hospitalization for heart failure, defined as elevation in creatinine during admission, predicts adverse outcomes. Prior studies define worsening renal function using various creatinine elevations, but the relative value of definitions is unknown.

Methods And Results: In a prospective cohort of 412 patients hospitalized for heart failure, we compared a spectrum of worsening renal function definitions (absolute creatinine elevations >/=0.

An integrated functional genomics screening program reveals a role for BMP-9 in glucose homeostasis.

A coordinated functional genomics program was implemented to identify secreted polypeptides with therapeutic applications in the treatment of diabetes. Secreted factors were predicted from a diverse expressed-sequence tags (EST) database, representing >1,000 cDNA libraries, using a combination of bioinformatic algorithms. Subsequently, approximately 8,000 human proteins were screened in high-throughput cell-based assays designed to monitor key physiological transitions known to be centrally involved in the physiology of type 2 diabetes.

4-(Phenylsulfonyl)piperidines: novel, selective, and bioavailable 5-HT(2A) receptor antagonists.

On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identified as high-affinity, selective 5-HT(2A) receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models.