Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene.

To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.

Regulation of human metabolism by hypoxia-inducible factor.

The hypoxia-inducible factor (HIF) family of transcription factors directs a coordinated cellular response to hypoxia that includes the transcriptional regulation of a number of metabolic enzymes. Chuvash polycythemia (CP) is an autosomal recessive human disorder in which the regulatory degradation of HIF is impaired, resulting in elevated levels of HIF at normal oxygen tensions. Apart from the polycythemia, CP patients have marked abnormalities of cardiopulmonary function.

Treatment with intravenous immunoglobulin and steroids may correct severe anemia in hyperhemolytic transfusion reactions: case report and literature review.

Hyperhemolytic transfusion reaction (HHTR) is a serious and potentially life-threatening complication of red blood cell (RBC) transfusion and has been well described in patients with sickle cell disease (SCD) and non-SCD patients. Awareness of this condition is important because subsequent transfusion may exacerbate hemolysis and may lead to a chronic protracted course or even death. If hemolysis is rapid and severe, subsequent transfusion may be necessary.

Transition to adult-oriented health care: perspectives of youth and adults with complex physical disabilities.

Introduction: The transition to adulthood is extremely difficult for individuals with disabilities. We sought to explore the specific issue of transition to adult-oriented health care in a Canadian context.

Methods: We conducted semi-structured individual interviews with 15 youth and 15 adults with cerebral palsy, spina bifida, and acquired brain injuries of childhood, and their parents (n = 30).

Synthesis of novel anilinoquinolines as c-fms inhibitors.

A novel series of potent substituted anilinoquinolines were discovered as c-fms inhibitors. The potency could be manipulated upon modification of the C4 aniline and C7 aryl functionality. Pharmacokinetic analysis identified a metabolically stable analog suitable for further investigative work.

The transition study: a look at youth and adults with cerebral palsy, spina bifida and acquired brain injury.

A group of 100 adults and 190 youth who have cerebral palsy (CP), spina bifida (SB), and acquired brain injuries from childhood (ABIc) participated in a multi-method study focused on the transition to adult health care. The results show that 95% of youth and 61% of adults were living with their parents; 23% of the youth and 55% of adults were employed; and 60% of youth and 42% of adults reported "excellent" or "very good" health. The lowest health scores were reported by adults with SB.

Synthesis and activity of small molecule GPR40 agonists.

The first report on the identification and structure-activity relationships of a novel series of GPR40 agonists based on a 3-(4-{[N-alkyl]amino}phenyl)propanoic acid template is described. Structural modifications to the original screening hit yielded compounds with a 100-fold increase in potency at the human GPR40 receptor and pEC(50)s in the low nanomolar range. The carboxylic acid moiety is not critical for activity but typically elicits an agonistic response higher than those observed with carboxamide replacements.

Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors.

A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar(1)) determined this to be a tight binding region with little room for modification.

Prevalence of tuberculosis, hepatitis B virus, and intestinal parasitic infections among refugees to Minnesota.

Objective: The purpose of this study was to define the prevalence of infection with Mycobacterium tuberculosis, hepatitis B virus, and various intestinal parasites among different groups of primary refugees immigrating to Minnesota.

Methods: 2,545 refugees arriving in Minnesota during 1999 received a domestic health examination that included tuberculin skin testing, hepatitis B virus serologic testing, and stool ova and parasite examinations. The Refugee Health Assessment form asked specifically about screening results for amebiasis, ascariasis, clonorchiasis, giardiasis, hookworm, schistosomiasis, strongyloidiasis, and trichuriasis.