Oligoribonucleotides containing 8-oxo-7,8-dihydroguanosine and 8-oxo-7,8-dihydro-2''-O-methylguanosine: synthesis and base pairing properties

OBJECTIVE: To test whether a rigid or a flexible ankle orthosis affects postural sway in single-limb stance as quantified by stabilometry. DESIGN: Crossover trial. SETTING: University laboratory. PARTICIPANTS: Twenty-two athletes with functional ankle instability (consecutive sample of patients with recurrent ankle sprains but without mechanical instability) and 22 healthy athletes (control group of volunteers matched to age, height, weight, physical activity). INTERVENTIONS: Stabilometry in single-limb stance on a force platform. Participants were tested on each leg with and without a rigid or a flexible ankle orthosis. The order of test conditions was randomized. MAIN OUTCOME MEASURES: Sway velocities, sway pattern, and sway area as calculated from center of pressure movements. The two groups were compared by Mann-Whitney test, and the different orthoses within each group were compared by Wilcoxon test, paired samples (type I error 5%, Bonferroni adjustment). RESULTS: In athletes with functional ankle instability, both a rigid and a flexible ankle orthosis significantly reduced mediolateral sway velocity. A flexible ankle orthosis also changed sway pattern significantly, by reducing the percentage of linear movements of less than 5 degrees per .01 sec. CONCLUSIONS: In athletes with functional ankle instability, ankle orthoses reduce mediolateral sway velocity, possibly because of improved mediolateral proprioception.     

L-tryptophan urea amides as NK1/NK2 dual antagonists

We report that a systematic modification of an NK1 receptor selective antagonist resulted in the identification of novel compounds, 4c and 4d, with high affinity for both NK1 and NK2 receptors.     

Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase

BACKGROUND: High level resistance to carbapenem antibiotics in gram negative bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide-spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co-administration of metallo-beta-lactamase inhibitors to resistant bacteria is expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl tetrazoles (BPTs) are a structural class of potent competitive inhibitors of metallo-beta-lactamase identified through screening and predicted using molecular modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts directly with one of the two zinc atoms in the active site, replacing a metal-bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro correlates well with antibiotic sensitization of resistant B. fragilis. CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical isolate expressing metallo-beta-lactamase to the antibiotics imipenem or penicillin G but not to rifampicin.     

Genetic influence on serum igd levels

In order to better understand the factors determining serum levels of IgD, total serum IgD and IgE were studied in 23 nonallergic twin pairs, consisting of 16 monozygotic (Mz and 7 same-sex dizygotic (Dz) pairs. Both immunoglobulins were measured by a paper disc solid phase radioimmunoassay, sensitive to 1 microgram/dl of IgD and 1 I.U./ml of IgE. Also studied were 10 paired sera taken at different times from 10 healthy subjects of similar mean age to the twins and 21 randomly paired sera from unrelated subjects. The intrapair variance of both serum IgD and serum IgE levels were significantly less in Mz than in Dz twins (P less than 0.05). Thus, there appears to be a genetic influence over serum IgD levels, probably to a similar degree to that previously shown to exist for serum IgE levels. Heritability was calculated to be 0.759 for IgD and 0.697 for IgE. Also, the intraclass correlation coefficient (rI) for IgD in monozygotic twin pairs was 0.9370 (P less than 0.001) and for IgE was 0.8602 (P less than 0.001). It appears likely that the number of genetic loci controlling serum IgD levels is similar to, or less than, the number controlling serum IgE levels because the random pair/Dz pair variance ratio was lower for IgD than for IgE.     

Quick-FISH: a rapid fluorescence in situ hybridization technique for molecular cytogenetic analysis

OBJECTIVE: To evaluate the pregnancy results of an ovarian hyperstimulation protocol for IVF-ET that combines GnRH agonist down-regulation, cessation of GnRH agonist therapy with the onset of menstruation, and high-dose gonadotropin administration in low responders. DESIGN: Prospective analysis. SETTING: Academic IVF program. PATIENT(S): One hundred eighty-two low responders undergoing 224 IVF-ET cycles. INTERVENTION(S): Down-regulation was obtained with the administration of leuprolide acetate beginning in the midluteal phase and ending with the onset of menses. Daily administration of 6 ampules of FSH alone or in combination with hMG was initiated on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation characteristics and pregnancy rates (PRs) were compared between fresh cycles in which pure FSH alone was used and 35 cycles in which a combination of FSH and hMG was administered. RESULT(S): The clinical PR per transfer, the ongoing PR per transfer, and the implantation rate were 32%, 24%, and 9%, respectively. No differences were noted between cycles in which pure FSH alone was used in comparison with cycles in which a combination of FSH and hMG was administered. CONCLUSION(S): Short-term ovarian suppression begun in the luteal phase and discontinued with the onset of menses followed by high-dose stimulation with gonadotropins yields favorable pregnancy results in low responders.     

Does the application of ground force set the energetic cost of cross-country skiing?

We tested whether the rate at which force is applied to the ground sets metabolic rates during classical-style roller skiing in four ways: 1) by increasing speed (from 2.5 to 4.5 m/s) during skiing with arms only, 2) by increasing speed (from 2.5 to 4.5 m/s) during skiing with legs only, 3) by changing stride rate (from 25 to 75 strides/min) at each of three speeds (3.0, 3.5, and 4.0 m/s) during skiing with legs only, and 4) by skiing with arms and legs together at three speeds (2.0-3.2 m/s, 1.5 degrees incline). We determined net metabolic rates from rates of O2 consumption (gross O2 consumption - standing O2 consumption) and rates of force application from the inverse period of pole-ground contact [1/tp(arms)] for the arms and the inverse period of propulsion [1/tp(legs)] for the legs. During arm-and-leg skiing at different speeds, metabolic rates changed in direct proportion to rates of force application, while the net ground force to counteract friction and gravity (F) was constant. Consequently, metabolic rates were described by a simple equation (metab = F . 1/tp . C, where metab is metabolic rates) with cost coefficients (C) of 8.2 and 0.16 J/N for arms and legs, respectively. Metabolic rates predicted from net ground forces and rates of force application during combined arm-and-leg skiing agreed with measured metabolic rates within +/-3. 5%. We conclude that rates of ground force application to support the weight of the body and overcome friction set the energetic cost of skiing and that the rate at which muscles expend metabolic energy during weight-bearing locomotion depends on the time course of their activation.     

California encephalitis virus proliferation in Yukon mosquitoes incubated at low temperatures

Replication of a subarctic Bunyavirus, California encephalitis (snowshoe hare subtype), was detected in salivary glands and thoraces of wild-caught Aedes communis mosquitoes from the Yokon Territory, after intrathoracic inoculation with 0.1 to 100 mouse LD50 virus, and incubation for 7 to 21 days throughout their viable temperature range of 0 to 23 degrees C. Immunoperoxidase staining confirmed that viral replication occurred in the cytoplasm of acinar cells of salivary glands, both by ligh microscopy and electron microscopy. Replication of another subarctic Bunyavirus, Northway, and a subtropical Flavivirus, Murray Valley encephalitis, was also demonstrated by infectivity by infectivity titrations and immun operoxidase reactions in salivary glands of A. communis incubated at 0, 13, and 23 degrees C for 7 to 21 days.