Speed Mentoring: An Effective & Efficient Path to Development of Mentor Relationships in a Military Obstetrics & Gynecology Residency.

Introduction: With a deficit of effective military residency mentorships, a paucity of research on successful mentorship programs, and growing reports on innovative mentoring programs, we developed a "Speed Mentoring" event for the National Capital Consortium OBGYN Residency.

Materials And Methods: The development, implementation, and follow-up responses through participant surveys were designed as an institutional review board (IRB)-approved evidence-based quality improvement project at our institution. Our event coordinated mentorship opportunities between residents and faculty from a wide range of specialties, leadership roles, and research experiences.

A Case of Intertwin Membrane Hemorrhage with Spontaneous Resolution.

Vaginal bleeding during pregnancy places women at increased risk of spontaneous abortion. Etiologies for threatened and spontaneous abortions have been well studied, but there is little information on intertwin membrane hemorrhage. We present a patient with a multiple gestation pregnancy who experienced first trimester vaginal bleeding with visualization and subsequent rapid resolution of an intertwin membrane hemorrhage.

Comment on "a peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys".

A study reporting that a peptidomimetic adipotide reduces weight loss in obese monkeys by inducing apoptosis of blood vessels surrounding white adipose tissue may instead reflect a direct effect of adipotide on food consumption.

Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritis.

Objective: To evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee.

Methods: Twenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS-5D4), aggrecan neoepitope (CS846), high-sensitivity C-reactive protein (hsCRP), osteocalcin, transforming growth factor beta1 (TGFbeta1), and type II collagen (CII)-related epitopes (neoepitope from cleavage of CII [C2C], carboxy-terminus of three-quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy-propeptide [CPII] in serum, and C-terminal telopeptides of CII [CTX-II] and C2C in urine).

Variation of serum hyaluronan with activity in individuals with knee osteoarthritis.

Purpose: Serum hyaluronan (HA) was evaluated for diurnal variation in participants with osteoarthritis (OA) of the knee.

Methods: Twenty participants with radiographic OA of at least one knee were admitted overnight to the General Clinical Research Center for serial serum sampling. Serum was obtained between 6:00 p.

B lymphocytes and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by B cell hyperactivity in association with autoantibodies, most prominently those directed to components of the cell nucleus. The source of the antigens that drive B cell responses in SLE is unknown, although recent studies suggest mechanisms by which the self-antigens become immunogenic and stimulate responses. Among these mechanisms, abnormalities in the generation of apoptotic cells or their clearance may increase the availability of nuclear antigens to drive responses.

Informed consent in a clinical trial of a novel treatment for rheumatoid arthritis.

Objective: To evaluate the informed consent process for a clinical trial of intravenous doxycycline for rheumatoid arthritis.

Methods: Participants completed a self-administered questionnaire about the consent process at baseline and 16 weeks following enrollment in a clinical trial.

Results: Respondents (n = 30) affirmed voluntary participation in the parent trial.

Tumor necrosis factor-alpha antagonists for the treatment of rheumatic diseases.

Tumor necrosis factor-alpha (TNF-alpha) antagonists have rapidly emerged as a valuable class of antirheumatic agents. Etanercept, a dimerized version of the soluble tumor necrosis factor receptor II, and infliximab, a chimeric anti-TNF-alpha monoclonal antibody, are currently approved for the treatment of rheumatoid arthritis (RA) based on their proven beneficial effects in clinical trials. New insights into the role of TNF-alpha in disease pathogenesis have expanded our understanding about the possible mechanisms by which these agents reduce synovial inflammation and inhibit bone and cartilage degradation.

Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists.

The design of a novel series of NPY-Y5 receptor antagonists is described. Key elements for the design were the identification of weak Y5 hits from a Y1 program, results from a combinatorial approach and database mining. This led to the discovery of the quinazoline 4 and the aryl-sulphonamide moiety as major components of the pharmacophore for Y5 affinity.

Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.

The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels.

The pharmacology of neuropeptide Y (NPY) receptor-mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes.

Thirteen neuropeptide Y (NPY) agonists were administered intracerebroventricularly (i.c.v.

Cytokines in murine lyme carditis: Th1 cytokine expression follows expression of proinflammatory cytokines in a susceptible mouse strain.

The cardiac infiltrate seen in murine Lyme carditis is composed predominantly of macrophages, but small numbers of T cells are also present. To identify the cytokines present in cardiac lesions from susceptible mice, semiquantitative polymerase chain reaction was done on cardiac tissue from mice infected with Borrelia burgdorferi. The temporal expression of proinflammatory and T cell-derived cytokines was characterized in cardiac tissue at days 0, 3, 7, 14, 21, and 42 after infection with B.

Inhibition of food intake by neuropeptide Y Y5 receptor antisense oligodeoxynucleotides.

The recently discovered rat neuropeptide Y (NPY) receptor, the Y5 subtype, has been proposed to mediate the NPY-induced feeding response and therefore plays a central role in the regulation of food intake. These conclusions were based on studies with peptidic agonists. We now report studies in which phosphothioate end-protected antisense oligodeoxynucleotides (ODNs) targeted to prepro NPY (prepro NPY antisense ODNs) or to the Y5 receptor (Y5 antisense ODNs) were used to assess the functional importance of this novel receptor subtype in vivo.

A receptor subtype involved in neuropeptide-Y-induced food intake.

Neuropeptide Y (NPY) is a powerful stimulant of food intake and is proposed to activate a hypothalamic 'feeding' receptor distinct from previously cloned Y-type receptors. This receptor was first suggested to explain a feeding response to NPY and related peptides, including NPY2-36, that differed from their activities at the Y1 receptor. Here we report the expression cloning of a novel Y-type receptor from rat hypothalamus, which we name Y5.

Mechanism of interaction between neuropeptide Y and angiotensin II in the rabbit femoral artery.

Neuropeptide Y has direct vasoconstrictor actions and potentiates the effects of other vasoconstrictor agents. To find out whether both effects of neuropeptide Y are mediated via the same receptor and intracellular mechanism, the interaction between neuropeptide Y and angiotensin II was studied in rabbit femoral arteries. In this preparation, neuropeptide Y, but not its 13-36 fragment, induced constriction.

Angiotensin blockade or calcium antagonists improve endothelial dysfunction in hypertension: studies in perfused mesenteric resistance arteries.

Endothelial regulation of peripheral vascular resistance is impaired in hypertension. We studied the effects of different antihypertensive therapies on endothelial function in perfused mesenteric resistance arteries. Spontaneously hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each 10 mg/kg/day orally, p.

Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.

Background: Coronary artery disease is an important complication of hypertension. Therefore, the effects of antihypertensive therapy on the endothelial nitric oxide (NO)/L-arginine pathway and vascular smooth muscle were studied in left anterior descending coronary arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Angiotensin II (AT1) receptor antagonists CGP 48369 and valsartan, angiotensin-converting enzyme inhibitor benazepril HCl, and calcium antagonist nifedipine were used as antihypertensive agents.

Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the angiotensin II AT1-receptor subtype.

1. The pharmacological profile of valsartan, (S)-N-valeryl-N-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl)-vali ne, a potent, highly selective, and orally active antagonist at the angiotensin II (AII) AT1-receptor, was studied in vitro and in vivo. 2.

Endothelium-dependent relaxant effect of neurokinins on rabbit aorta is mediated by the NK1 receptor.

Several neurokinins, namely substance P, neurokinin A, neurokinin B, [beta-Ala8]neurokinin A-(4-10) and senktide, were tested on noradrenaline-precontracted rabbit aortic rings to characterize the receptor mediating their endothelium-dependent relaxant effect in this preparation. CP-96,345, the new nonpeptide antagonist selective for the NK1 receptor, was also studied. Substance P, neurokinin A and neurokinin B, in that order of potency, were effective in relaxing precontracted rings, indicating the involvement of the NK1 receptor; [beta-Ala8]neurokinin A-(4-10) and senktide, which are selective agonists for NK2 and NK3 receptors, respectively, had no significant relaxant effect.

Sensitivity and reactivity to endothelin-1 in mesenteric beds and aortic rings of 4-week-old spontaneously hypertensive rats.

The vasoconstrictor effects of endothelin-1 were studied in perfused mesenteric vascular beds (MVB) and aortic rings of 4-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Mean blood pressure (124 +/- 4 vs. 97 +/- 3 mmHg) and initial perfusion pressure in the MVBs (25 +/- 2 vs.

Nonpeptidic angiotensin II antagonists: synthesis and in vitro activity of a series of novel naphthalene and tetrahydronaphthalene derivatives.

Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparations as well as inhibition of angiotensin II induced contraction of rabbit aortic rings was measured and the order of potency was compared with predictions made on the basis of a molecular modeling study. In good agreement with the predictions, the 2,6-substituted regioisomer 6d and its analogue 7 (isomeric at the imidazole substituent) were found to be most potent, but were still weaker than DuP 753.