Sildenafil inhibits superoxide formation and prevents endothelial dysfunction in a mouse model of secondhand smoke induced erectile dysfunction.

Purpose: We determined the effect of passive secondhand cigarette smoke on 1) erectile function in vivo, 2) molecular mechanisms involved in penile vascular function, and 3) erectile function and penile molecular signaling in the presence of phosphodiesterase type 5 inhibitor therapy.

Materials And Methods: Four groups of mice were used, including group 1--controls, group 2--mice exposed to 3 weeks of secondhand smoke (5 hours per day for 5 days per week), group 3--control plus sildenafil (100 mg/kg per day) and group 4--smoke exposed plus sildenafil (100 mg/kg per day). Cavernous nerve electrical stimulation and intracavernous injection of acetylcholine were done to assess erectile function.

Hypothyroidism and dyshormonogenesis induced by D-penicillamine in children with Wilson's disease and healthy infants born to a mother with Wilson's disease.

Two siblings born to a mother with Wilson's disease, who was taking D-penicillamine, developed transient goitrous hypothyroidism. A prospective evaluation of 5 patients with Wilson's disease taking and not taking D-penicillamine for as long as 9.5 years showed subclinical hypothyroidism.

Increased oxidant activity mediates vascular dysfunction in vibration injury.

Occupational exposure to hand-operated vibrating tools causes a spectrum of pathological changes in the vascular, neurological, and musculoskeletal systems described as the hand-arm vibration syndrome (HAVS). Experiments were performed to determine the effects of acute vibration on the function of digital arteries. Rats paws were exposed to a vibrating platform (4 h, 125 Hz, constant acceleration of 49 m/s(2) root mean squared), and digital artery function was assessed subsequently in vitro using a pressure myograph system.

Nutritional supplementation with polymeric diet enriched with transforming growth factor-beta 2 for children with Crohn's disease.

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFbeta2-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD as a supplement to their regular nutrition.

Arginase and vascular aging.

Vascular and associated ventricular stiffness is one of the hallmarks of the aging cardiovascular system. Both an increase in reactive oxygen species production and a decrease in nitric oxide (NO) bioavailability contribute to the endothelial dysfunction that underlies this vascular stiffness, independent of other age-related vascular pathologies such as atherosclerosis. The activation/upregulation of arginase appears to be an important contributor to age-related endothelial dysfunction by a mechanism that involves substrate (L-arginine) limitation for NO synthase (NOS) 3 and therefore NO synthesis.

Selective fluorescent labeling of S-nitrosothiols (S-FLOS): a novel method for studying S-nitrosation.

Protein S-nitrosation is a reversible post-translation modification critical for redox-sensitive cell signaling that is typically studied using the Biotin Switch method. This method and subsequent modifications usually require avidin binding or Western blot analysis to detect biotin labeled proteins. We describe here a modification of the Biotin Switch assay that eliminates the need for Western blot or avidin enrichment protocols and allows direct comparison of the S-nitrosation state proteins from two different samples in the same gel lane or on the same 2D gel.

Early performance of voiding cystourethrogram after urinary tract infection in children.

Background: Voiding cystourethrogram is performed 3-6 weeks after urinary tract infection. This prolongs the interval of prophylactics, reducing the likelihood of having to perform the procedure.

Objectives: To investigate the yield and potential risks/benefits of early compared to late performance of VCUG after UTI.

Assessing mandatory HPV vaccination: who should call the shots?

In 2007, many legislatures considered, and two enacted, bills mandating HPV vaccination for young girls as a condition of school attendance. Such mandates raise significant legal, ethical, and social concerns. This paper argues that mandating HPV vaccination for minor females is premature since long-term safety and effectiveness of the vaccine has not been established, HPV does not pose imminent and significant risk of harm to others, a sex specific mandate raises constitutional concerns, and a mandate will burden financially existing government health programs and private physicians.

Accurate characterization of extravascular lung water in acute respiratory distress syndrome.

Objectives: Measurements of extravascular lung water (EVLW) correlate to the degree of pulmonary edema and have substantial prognostic information in critically ill patients. Prior studies using single indicator thermodilution have reported that 21% to 35% of patients with clinical acute respiratory distress syndrome (ARDS) have normal EVLW (<10 mL/kg). Given that lung size is independent of actual body weight, we sought to determine whether indexing EVLW to predicted or adjusted body weight affects the frequency of increased EVLW in patients with ARDS.

Endothelial arginase II: a novel target for the treatment of atherosclerosis.

Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E-null (ApoE(-/-)) and wild-type mice fed a high cholesterol diet. In ApoE(-/-) mice, selective arginase II inhibition or deletion of the arginase II gene (Arg II(-/-) mice) prevents high-cholesterol diet-dependent decreases in vascular NO production, decreases endothelial reactive oxygen species production, restores endothelial function, and prevents oxidized low-density lipoprotein-dependent increases in vascular stiffness.

A set of phosphatase-inert "molecular rulers" to probe for bivalent mannose 6-phosphate ligand-receptor interactions.

A set of bivalent mannose 6-phosphonate 'molecular rulers' has been synthesized to examine ligand binding to the M6P/IGF2R. The set is estimated to span a P-P distance range of 16-26A (MMFF energy minimization on the hydrated phosphonates). Key synthetic transformations include sugar triflate displacement for phosphonate installation and Grubbs I cross-metathesis to achieve bivalency.

Large-volume thoracentesis and the risk of reexpansion pulmonary edema.

Background: To avoid reexpansion pulmonary edema (RPE), thoracenteses are often limited to draining no more than 1 L. There are, however, significant clinical benefits to removing more than 1 L of fluid. The purpose of this study was to define the incidence of RPE among patients undergoing large-volume (> or = 1 L) thoracentesis.

Mitochondrial arginase II constrains endothelial NOS-3 activity.

Emerging evidence supports the idea that arginase, expressed in the vascular endothelial cells of humans and other species, modulates endothelial nitric oxide (NO) synthase-3 (NOS-3) activity by regulating intracellular L-arginine bioavailability. Arginase II is thought to be expressed in the mitochondria of a variety of nonendothelial cells, whereas arginase I is known to be confined to the cytosol of hepatic and other cells. The isoforms that regulate NOS-3 and their subcellular distribution, however, remain incompletely characterized.

Pulse pressure is an age-independent predictor of stroke development after cardiac surgery.

Chronologic age is a strong predictor of adverse outcomes after cardiac surgery. The variability in age-related cardiovascular changes suggests that age may not be the most accurate predictor of adverse perioperative outcomes. Vascular stiffness has emerged as an important surrogate of vascular aging.

Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction.

Endothelial function is impaired in aging because of a decrease in NO bioavailability. This may be, in part, attributable to increased arginase activity, which reciprocally regulates NO synthase (NOS) by competing for the common substrate, L-arginine. However, the high Km of arginase (>1 mmol/L) compared with NOS (2 to 20 micromol/L) seemingly makes direct competition for substrate unlikely.

"Cassette" in situ enzymatic screening identifies complementary chiral scaffolds for hydrolytic kinetic resolution across a range of epoxides.

‘Cassette’-ISES (In Situ Enzymatic Screening) Identifies Complementary Chiral Scaffolds for Hydrolytic Kinetic Resolution Across a Range of Epoxides A new ‘Cassette’-In Situ Enzymatic Screen (ISES) for combinatorial catalysis is introduced. This allows the experimentalist to obtain an information-rich readout, in real time, providing an estimate of the sense and magnitude of enantioselectivity across more than one substrate. In its first iteration, the screen identified Co-salen catalysts with β-pinene- and α-naphthylalanine-derived chiral scaffolds with broad, yet complementary, substrate specificities.

The interaction of drag queens and gay men in public and private spaces.

This study examines the issue of internal segregation within the gay community, focusing on the ways by which the drag queen subculture is distanced from larger mainstream gay society. Through the use of institutional ethnography, symbolic interactionism, and a naturalist approach to sociology, the researchers sought to understand the subjective experience of the drag queen, in particular how drag queens perceive their interactions with mainstream gay society. Data for this study were collected through a series of observations conducted in a variety of spatial contexts and interviews with 18 drag queens.

Topoisomerase II - drug interaction domains: identification of substituents on etoposide that interact with the enzyme.

Etoposide is one of the most successful chemotherapeutic agents used for the treatment of human cancers. The drug kills cells by inhibiting the ability of topoisomerase II to ligate nucleic acids that it cleaves during the double-stranded DNA passage reaction. Etoposide is composed of a polycyclic ring system (rings A-D), a glycosidic moiety at the C4 position, and a pendent ring (E-ring) at the C1 position.

Effects of synthetic conjugated estrogens A on sleep quality in postmenopausal women with nocturnal diaphoresis and/or hot flushes: a pilot study.

In a single-center, double-blind, placebo-controlled pilot study, patients who received 0.625 mg daily of synthetic conjugated estrogens A experienced a statistically significant reduction in the average number of hot flushes and galvanic skin responses. The polysomnographic change in sleep measures did not reach statistical significance, but the data suggest an overall improvement in sleep quality in the treatment group.

Imaging features of posterior mediastinal chordoma in a child.

A 5 1/2-year-old boy presented with repeated episodes of stridor and cough. Chest radiography demonstrated a widened mediastinum. Evaluation by CT revealed a low-density posterior mediastinal mass initially diagnosed as benign tumor.