Incidence of exercise-induced bronchospasm in Olympic winter sport athletes.

PURPOSE: The purpose of this project was to determine the incidence of exercise-induced bronchospasm (EIB) among U.S. Olympic winter sport athletes. METHODS: Subjects included female and male members of the 1998 U.S. Winter Olympic Team from the following sports: biathlon, cross-country ski, figure skating, ice hockey, Nordic combined, long-track speedskating, and short-track speedskating. Assessment of EIB was conducted in conjunction with an "actual competition" (Olympic Trials, World Team Trials, World Cup Event, U.S. National Championships) or a "simulated competition" (time trial, game), which served as the exercise challenge. Standard spirometry tests were performed preexercise and at 5, 10, and 15 min postexercise. An athlete was considered EIB-positive based on a postexercise decrement in FEV1 > or = 10%. RESULTS: For the seven sports evaluated on the 1998 U.S. Winter Olympic Team, the overall incidence of EIB across all sports and genders was 23%. The highest incidence of EIB was found in cross-country skiers, where 50% of the athletes (female = 57%; male = 43%) were diagnosed with EIB. Across the seven sports evaluated, the prevalence of EIB among the female and male athletes was 26% and 18%, respectively. Among those individuals found to be EIB-positive were athletes who won a team gold medal, one individual silver medal, and one individual bronze medal at the Nagano Winter Olympics. CONCLUSIONS: These data suggest that: 1) EIB is prevalent in several Olympic winter sports and affects nearly one of every four elite winter sport athletes; 2) the winter sport with the highest incidence of EIB is cross-country skiing; 3) in general, EIB is more prevalent in female versus male elite winter sport athletes; and 4) athletes may compete successfully at the international level despite having EIB.

Effect of altitude training on serum creatine kinase activity and serum cortisol concentration in triathletes.

In this investigation we evaluated the effect of a 5-week training program at 1860 m on serum creatine kinase (CK) activity and serum cortisol concentration in national-caliber triathletes for the purpose of monitoring the response to training in a hypobaric hypoxic environment. Subjects included 16 junior-level female (n = 8) and male (n = 8) triathletes who were training for the International Triathlon Union (ITU) World Championships. After an initial acclimatization period, training intensity and/or volume were increased progressively during the 5-week altitude training camp. Resting venous blood samples were drawn at 0700 hours following a 12-h overnight fast and were analyzed for serum CK activity and serum cortisol concentration. Subjects were evaluated before [7-10 days pre-altitude (SL 1)] and after [7-10 days post-altitude (SL 2)] the 5-week training camp at 1860 m. At altitude, subjects were evaluated within 24-36 h after arrival (ALT 1), 7 days after arrival (ALT 2), 18 days after arrival (ALT 3), and 24-36 h prior to leaving the altitude training camp (ALT 4). A repeated-measures analysis of variance was used to evaluate differences over time from SL 1 to SL 2. Compared to SL 1, serum CK activity increased approximately threefold (P < 0.05) within the initial 24-36 h at altitude (ALT 1), and increased by an additional 70% (P < 0.05) after the 1st week of altitude training (ALT 2). Serum CK activity remained significantly elevated over the duration of the experimental period compared to pre-altitude baseline levels. Serum cortisol concentration was increased (P < 0.05) at the end of the 5-week altitude training period (ALT 4) relative to SL 1, ALT 1 and ALT 3. These data suggest that: (1) the initial increase in serum CK activity observed in the first 24-36 h at altitude was due primarily to acute altitude exposure and was independent of increased training intensity and/or training volume, (2) the subsequent increases in serum CK activity observed over the duration of the 5-week altitude camp were probably due to the combined effects of altitude exposure and increased training load, and (3) the increase in serum cortisol concentration observed at the end of the altitude training camp reflects the additive effect of 5 weeks of altitude exposure in combination with a progressively increased training intensity and/or volume.

Alectosarmentin, a new antimicrobial dibenzofuranoid lactol from the lichen, Alectoria sarmentosa.

From the alcoholic extract of the lichen Alectoria sarmentosa, four compounds showing antimicrobial activity were isolated. Of these, (-)-usnic acid and physodic acid are well known lichen products, 8'-O-ethyl-beta-alectoronic acid [2] is believed to be an artifact formed during isolation and fractionation, and alectosarmentin [1] is a new natural product whose structure was shown, by spectroscopy and chemical transformations, to be that of a dibenzofuranoid lactol. The antimicrobial activity of these substances accounts for the activity of the lichen.

Streptonigrin and lavendamycin partial structures. Probes for the minimum, potent pharmacophore of streptonigrin, lavendamycin, and synthetic quinoline-5,8-diones.

The preparation and evaluation of 7-amino-5,8-dioxo-2-(2'-pyridyl)quinoline-6'-carboxylic acid (5a) and 7-amino-2-(2'-aminophenyl)-5,8-dioxoquinoline-5'-carboxylic acid (6a) constituting potential minimum, potent pharmacophores of streptonigrin (1a) and lavendamycin (2a), two structurally related naturally occurring antitumor antibiotics, are detailed. In contrast to observations associated with streptonigrin and lavendamycin in which the C-ring C-6' carboxylic acid potentiates the antitumor, antimicrobial, and cytotoxic properties of the naturally occurring, substituted 7-aminoquinoline-5,8-dione AB ring systems, the C-6'/C-5' carboxylic acid of 5a/6a diminishes the observed antimicrobial and cytotoxic properties of the 2-(2'-pyridyl)- and 2-(2'-aminophenyl)-7-aminoquinoline-5,8-diones. A direct comparison of the antimicrobial and cytotoxic properties of a complete set of streptonigrin and lavendamycin partial structures is detailed in efforts to define the role peripheral substituents play in potentiating the biological properties of the naturally occurring and synthetic agents bearing the 7-aminoquinoline-5,8-dione AB ring system and in efforts to define the minimum, potent pharmacophore of the naturally occurring antitumor antibiotics. The relationship of these observations to a chemical mechanism of cellular toxicity is discussed.

Antimicrobial and cytotoxic properties of 9,10-dihydrophenanthrenes: structure-activity studies on juncusol.

The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-hydroxy-3-methyl-9,10-dihydrophenanthrene (3h), were found to possess in vitro antimicrobial activity comparable with that of the natural product. Two 9,10-dihydrophenanthrenes substituted with quaternary ammonium salts, 2d and 3d, each containing a reactive benzylic dimethyl[(phenylthio)methyl]ammonio group, were found to be 10-20 times more potent than juncusol (1a). Confirmed in vitro cytotoxic activity that parallels antimicrobial activity was found for juncusol (1a), desvinyljuncusol (2h), 2-hydroxy-3-methyl-9,10-dihydrophenanthrene (3h), and the quaternary dimethyl[(phenylthio)methyl]ammonium salts 2d and 3d in a human lymphoblastic leukemia cell culture (CCRF-CEM, IC50 = nt, 9.3, nt, 0.9 and 1.4 microgram/mL, respectively), B-16 mouse melanoma cell culture (IC50 = 12.5, 17.5, 27.7, 0.3, and 0.5 microgram/mL, respectively), and L-1210 mouse lymphocytic leukemia cell culture (IC50 = 13.8, 10.2, 24.5, 1.3, and 3.7 micrograms/mL, respectively). The comparable potency and spectrum of activity of juncusol (1a), desvinyljuncusol (2h), and 2-hydroxy-3-methyl-9,10-dihydrophenanthrene (3h) suggest that the agents are acting as simple phenols in exerting their antimicrobial and cytotoxic effects.

Structure-activity relationships among DNA gyrase inhibitors. Synthesis and biological evaluation of 1,2-dihydro-4, 4-dimethyl-1-oxo-2-naphthalenecarboxylic acids as 1-carba bioisosteres of oxolinic acid.

A series of oxolinic acid analogues was synthesized in an attempt to evaluate the role, if any, played by the N-1 atom in putative modes of action of antimicrobial DNA gyrase inhibitors. Carba analogues were prepared because these have no possibility of an internal resonance contribution of the nitrogen atom and yet could otherwise satisfy electronic requirements of putative modes of action. Successful routes were developed involving Friedel-Craft's cycloaddition of suitable aromatic compounds with 4,4-dimethylbutyrolactone, followed by ethoxycarbonylation, oxidation with dichlorodicyanobenzoquinone, and careful saponification. The gem-dimethyl group of these analogues prevents aromatization at the cost of nonplanarity. Only the unsubstituted parent compound, 1,2-dihydro-4,4-dimethyl-1-oxo-2-naphthalenecarboxylic acid, possessed any appreciable antimicrobial activity in vitro. This may be due to a different mode of action, however, since gave no measurable inhibition of DNA gyrase in vitro. Thus, the N-1 atom plays a significant role in enzymic and bacteriological inhibition that cannot be compensated for by the presence of C-6 oxygen atoms.

Quinolone antimicrobial agents. 2. Methylenedioxy positional isomers of oxolinic acid.

The synthesis and antimicrobial activity of the methylenedioxy positional isomers, 1-ethyl-1,4-dihydro-5,6-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (9) and 1-ethyl-1,4-dihydro-7,8-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (17), of oxolinic acid (18) have been accomplished. Isomer 9 was prepared by the reaction of N-ethyl-6,7-methylenedioxyisatoic anhydride with sodioethyl formylacetate [L. A. Mitscher, H. E. Gracey, G. W. Clark III, and T. Suzuki, J. Med. Chem., 21, 485 (1978)], while isomer 17 was prepared by thermal cyclization of diethyl 2-[(2,3-methylenedioxyanilino)methylene]malonate [D. Kaminsky and R. I. Meltzer, J. Med. Chem., 11, 160 (1968)]. Both of the new isomers are less active in vitro when compared to oxolinic acid (18) itself.