Sexual violence in sport: American Medical Society for Sports Medicine Position Statement.

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a Position Statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the Task Force used an iterative process and expert consensus to finalise the Position Statement. The objective of this Position Statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.

Conserved CRISPR arrays in Salmonella enterica serovar Infantis can serve as qPCR targets to detect Infantis in mixed serovar populations.

Salmonellosis is a leading bacterial cause of foodborne illness, and numerous Salmonella enterica serovars have been responsible for foodborne outbreaks. In the United States outbreaks are often linked to poultry and poultry-related products. The prevalence of Salmonella serovar Infantis has been increasing in poultry processing facilities over the past few years and in 2018 was identified as the causative agent for a large multistate outbreak linked to raw chicken. CRISPR-typing is a subtyping approach based on PCR and the sequencing of two Salmonella loci, CRISPR1 and CRISPR2. CRISPR-typing was used to interrogate 138 recent (2018-2019) isolates and genomes of ser. Infantis. Results show that the CRISPR elements are remarkably conserved in this serovar. The most conserved spacers, and those also unique to ser. Infantis, were used as targets to develop a ser. Infantis-specific qPCR assay. This assay was able to detect ser. Infantis in mixed serovar cultures of Salmonella, down to 0·1% of the population, highlighting the utility of this molecular approach in improving surveillance sensitivity for this important food safety pathogen. SIGNIFICANCE AND IMPACT OF THE STUDY: The incidence of human salmonellosis cases caused by Salmonella enterica serovar Infantis (ser. Infantis) has been increasing, as has its prevalence in broiler chickens, which are a frequent reservoir of Salmonella. A cluster of ser. Infantis genetically linked to an outbreak strain have been identified in numerous processing facilities. A qPCR assay targeting CRISPR elements that are unique to ser. Infantis has been developed and can detect this serovar directly from mixed cultures. This assay is sensitive enough to reveal ser. Infantis within a mixed Salmonella population where it constitutes only 0·1% of the population. The rapid nature of qPCR lends this assay to high-throughput screening of poultry samples to detect this important pathogen.

Effect of supplementing pasteurized milk balancer products to heat-treated whole milk on the growth and health of dairy calves.

Two experiments were conducted to determine the growth and health effects of supplementing heat-treated whole milk with pasteurized milk balancer products in calf-feeding programs. All calves were removed from their dams at birth (d 0), fed 3.8L of heat-treated colostrum, and received assigned treatments from d 1 until weaning at d 56. Calves were weighed and skeletal measurements taken every 7 d from d 0 until 56. Average daily gain (ADG) and feed efficiency (FE) were calculated. In experiment 1, 80 Holstein heifer calves were used to investigate the effects of supplementing 2 levels of heat-treated whole milk with or without a pasteurized all-milk balancer. Four dietary treatments (n=20) were used. Calves receiving milk (M) and milk plus balancer (M+B) were fed 3.8L of milk divided into 2 equal feedings daily. Calves fed increased milk (IM) and increased milk plus balancer (IM+B) received 3.8L of milk divided into 2 equal feedings from d 1 to 14, 5.7L from d 15 to 42, and 2.85L fed once daily from d 43 to 56. Treatments M+B and IM+B included pasteurized all-milk balancer fed at a rate of 0.23kg per 3.8L of milk. In experiment 2, 72 Holstein heifer calves were used to investigate the effects of supplementing either a pasteurized all-milk balancer or a pasteurized protein-blend milk balancer. Three dietary treatments (n=24) were used. Calves were fed 3.8L of milk divided into 2 equal feedings from d 1 to 14 and 5.7L from d 15 to 56. Treatment IM did not include any supplements. Balancer was added to IM+B and increased milk plus protein-blend balancer (IM+PB). Balancer was supplemented at a rate of 0.23kg per 3.8L of milk. In experiment 1, calves fed IM+B had greater average body weight (BW) and average daily gain compared with calves given other treatments. Calves fed 5.7L of milk had greater FE than those fed 3.8L regardless of balancer added. In experiment 2, calves fed IM+B and IM+PB had greater BW when compared with calves given M. Calves fed IM+PB had comparable BW and FE to calves given IM+B. The enhanced calf-feeding programs evaluated in this study were successful in increasing growth in preweaned calves when supplementing milk balancer product to heat-treated whole milk. Health scores of fecal, respiratory, and attitude determined illness. Feces were looser for calves receiving IM+B and IM+PB, but attitude scores did not confirm an illness and so overall health was not different between treatments.

Efficacy of pyramided Bt proteins Cry1F, Cry1A.105, and cry2Ab2 expressed in Smartstax corn hybrids against lepidopteran insect pests in the northern United States.

Commercial field corn (Zea mays L.) hybrids transformed to express some or all of the lepidopteran insect-resistant traits present in SmartStax corn hybrids were evaluated for insecticidal efficacy against a wide range oflepidopteran corn pests common to the northern United States, during 2008 to 2011 at locations in 15 states. SmartStax hybrids contain a pyramid of two Bacillus thuringiensis (Bt) derived events for lepidopteran control: event TC1507 expressing Cry1F protein and MON 89034 expressing CrylA.105 + Cry2Ab2. These studies focused on characterization of the relative efficacy of each event when expressed alone or in combination, and compared with non-Bt hybrid. Corn hybrids containing pyramided insecticidal proteins Cry1F + Cry1A.105 + Cry2Ab2 (SmartStax) consistently showed reduced plant feeding damage by a wide range of lepidopteran larvae compared with single event and non-Bt hybrids. Corn hybrids expressing TC1507 or MON 89034 as single or pyramided events were consistently efficacious against Ostrinia nubilalis (Hübner). SmartStax hybrids had less injury from Agrotis ipsilon (Hufnagel) and Striacosta albicosta (Smith) than corn hybrids containing only event MON 89034 but were not more efficacious than single event TC1507 hybrids. Corn hybrids with event MON 89034 provided better control of Helicoverpa zea (Boddie), than event TC1507 alone. Spodoptera frugiperda (J.E. Smith) efficacy was higher for hybrids with pyramid events and single events compared with the non-Bt hybrids. The spectra of activity of events TC1507 and MON 89034 differed. The combination of TC1507 + MON 89034 provided redundant control of some pests where the spectra overlapped and thereby are expected to confer a resistance management benefit.

Granulomatous typhlocolitis, lymphangitis, and lymphadenitis in a horse infected with Listeria monocytogenes, Salmonella Typhimurium, and cyathostomes.

A 15-year-old American Quarter horse mare was euthanized because of poor response to therapy for severe diarrhea. Significant gross findings were limited to the large intestines. The walls of the cecum and colon were thickened with widely scattered nodules in the mucosa and submucosa that extended into the enlarged colic lymph nodes. Microscopically, there was severe granulomatous typhlocolitis, lymphangitis, and lymphadenitis, with many intralesional Gram-positive, non-acid-fast coccobacilli and few cyathostomes. Intralesional bacteria were immunohistochemically and polymerase chain reaction (PCR) assay positive for Listeria monocytogenes. Concurrent infection with Salmonella enterica serovar Typhimurium was detected by PCR and culture. Infection with L. monocytogenes in horses is rare, and coinfection with Salmonella and small strongyles probably contributed to the development of granulomatous typhlocolitis.

Effect of experimental feed additives on aflatoxin in milk of dairy cows fed aflatoxin-contaminated diets.

Three studies were conducted to determine the potential of experimental feed additives (EFAs), clays or non-digestible yeast oligosaccharides, to reduce milk aflatoxin (AFM1) concentrations in lactating Holstein cows consuming aflatoxin-contaminated diets. All studies included a pre-treatment period and a 2-week experimental period in a randomized block design. During the pre-treatment period, cows received a total mixed ration (TMR) with no aflatoxin contamination. During both experimental weeks, all cows were fed a TMR containing aflatoxin-contaminated corn. During experimental week 1, cows received no EFA's in the TMR, but EFA's were included in the TMR for the second experimental week. In studies 1 and 2, the experimental period consisted of 2 weeks each lasting 7 days with 12 cows per treatment. Aflatoxin M1 concentrations were analysed by HPLC for milk samples collected on days 5-7 and days 11-14. In various experiments, treatments included control (no EFA), 100 g/cow daily of experimental Lallemand(®) product, 10 g/cow daily of MTB-100(®) -2004, (Alltech, Inc.), 10 g/cow daily of MTB-100(®) -2006, (Alltech, Inc.), 10 g/cow daily of experimental Alltech(®) product (Alltech, Inc.) and 227 g/cow daily of Astra-Ben 20(®) (AB-20(®) ; Prince Agri Products, Inc.). In study 3, the experimental period of 2 weeks each lasting 8 days and milk samples were collected from day 4 to 8 and day 11 to 16. Milk samples from study 3 were analysed for AFM1 concentrations by ELISA. For all experiments, changes in AFM1 concentrations because of the addition of EFA's were calculated. Four of the five EFAs tested in this study had no significant effect on AFM1 concentrations. However, the addition of AB-20(®) resulted in a significant decrease in AFM1 concentrations (60.4%). In summary, the addition of AB-20(®) to the diet of cattle appears to be effective for significantly reducing AFM1 concentrations in the milk of cows fed an aflatoxin-contaminated diet.

Field evaluation of the accuracy of vaccine deposition by two different commercially available in ovo injection systems.

The location of injection and vaccine deposition in ovo is known to be critical to the efficacy of Marek's disease (MD) vaccine protection against MD viral challenge. Vaccine deposition into the amniotic sac or a s.c. or i.m. site of the embryo is required for MD vaccine efficacy. Vaccine deposition into the air cell or allantoic fluid results in chicks that are not adequately protected against subsequent MD viral challenge. A study was conducted in 2 commercial broiler hatcheries to evaluate the ability of 2 in ovo injection systems, the Embrex Inovoject system (Pfizer Poultry Health, Research Triangle Park, NC) and the Intelliject system (Avitech, Salisbury, MD; distributed by Merial Ltd., Gainesville, GA) to deliver a vaccine approved for use in ovo accurately and properly. A standard MD vaccine diluent mixed with a protein-staining dye was delivered through each machine to simulate in ovo vaccination. The location of the dye within the egg determined whether the vaccine was delivered correctly. Each egg was also evaluated for normal embryo development (normal eggs). Correct vaccine delivery included eggs in which the vaccine was injected into the amniotic sac or into s.c. or i.m. regions of the embryo. Incorrect vaccine delivery was defined as delivery into the air cell; allantoic sac; any combinations including air cell or allantois; the abdominal, cranial, orbital, or thoracic cavities of the embryo; or no vaccine delivery at all. In hatchery 1 (Chick Master, Newton, MS) 1,171 normal eggs were processed through the Inovoject system and 1,138 eggs were processed by the Intelliject system. The Inovoject system correctly vaccinated 94.62% of the normal eggs as compared with 61.16% delivery accuracy of normal eggs with the Intelliject system. In hatchery 2 (Jamesway Super J, Magee, MS) 926 normal eggs were processed by the Inovoject system and 910 normal eggs were processed by the Intelliject system. The Inovoject system correctly vaccinated 91.04% of the normal eggs, whereas the Intelliject system correctly vaccinated 71.98% of the normal eggs. The results of this study clearly demonstrate that the Inovoject system accurately delivered in ovo vaccine at a significantly higher rate than the Intelliject system.

Slight differences in incubation temperature affect early growth and stress endocrinology of wood duck (Aix sponsa) ducklings.

Early developmental experiences, such as incubation conditions, can have important consequences for post-hatching fitness in birds. Although the effects of incubation temperature on phenotype of avian hatchlings are poorly understood, recent research suggests that subtle changes in incubation conditions can influence hatchling characteristics, including body size and condition. We designed an experiment to explore the effects of incubation temperature on hatching success, survival to 9 days post hatch, growth and the hypothalamo-pituitary-adrenal (HPA) axis in wood ducks (Aix sponsa). Wood duck eggs were collected from nest boxes and experimentally incubated at three temperatures (35.0, 35.9 and 37.0 degrees C), each falling within the range of temperatures of naturally incubated wood duck nests. Survival and growth were monitored in ducklings fed ad libitum for 9 days post hatch. In addition, baseline and stress-induced plasma corticosterone concentrations were measured in 2 and 9 day old ducklings. Hatching success and survival to 9 days was greatest in ducks incubated at the intermediate temperature. Ducklings incubated at 35.9 degrees C and 37.0 degrees C had 43% higher growth rates than ducklings incubated at 35.0 degrees C. In addition, ducklings incubated at 35.0 degrees C had higher baseline (17-50%) and stress-induced (32-84%) corticosterone concentrations than ducklings incubated at 35.9 degrees C and 37.0 degrees C at 2 and 9 days post hatch. We also found a significant negative correlation between body size and plasma corticosterone concentrations (baseline and stress-induced) in 9 day old ducklings. To our knowledge, this is the first study to demonstrate that thermal conditions experienced during embryonic development can influence the HPA axis of young birds. Our results illustrate that subtle changes (<1.0 degrees C) in the incubation environment can have important consequences for physiological traits important to fitness.

Baby swimming: exploring the effects of early intervention on subsequent motor abilities.

AIM: The aim of the study was to explore the effects of baby swimming on subsequent motor abilities. BACKGROUND: A range of motor abilities was examined in 4-year-old children who had previously participated in a programme of baby swimming (n= 19) and compared with a matched group of coevals who had not had this experience (n= 19). RESULTS: As predicted from the nature of the exercises that comprise the programme, the effects of baby swimming were restricted to abilities associated with prehension and balance. CONCLUSIONS: Suggestions are made as to how the theme of this hypothesis-generating, demonstration study can be pursued in the future with more rigorous experimental controls and applications to children with disabilities and impairments.

Sexual Violence in Sport: American Medical Society for Sports Medicine Position Statement.

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a position statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the task force used an iterative process and expert consensus to finalize the position statement. The objective of this position statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.

ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability: implications for a link between cartilage and subchondral bone changes.

OBJECTIVE: Osteoarthritis (OA) is characterized by damaged articular cartilage and changes in subchondral bone. Previous work demonstrated aggrecanase-2 deficient (ADAMTS5-/-) mice to be protected from cartilage damage induced by joint instability. This study analyzed whether this protective effect on cartilage is also reflected in the subchondral bone structure. METHODS: Right knee joints from 10-week old male wild type (WT) and ADAMTS5-/- mice received transection of the medial meniscotibial ligament to induce OA, whereas left knees were left unoperated. After 8 weeks knee joints were scanned by micro-CT. The proximal tibia was selected for further analysis. Histology was performed to evaluate cartilage damage and osteoclast presence. RESULTS: ADAMTS5-/- joints had a significantly thinner subchondral plate and less epiphyseal trabecular bone compared to WT joints. Histology confirmed previous findings that ADAMTS5-/- mice have significantly less cartilage damage than WT in the instability-induced OA model. Although the subchondral bone plate became significantly thicker at the medial tibial plateau in operated joints of both genotypes, the percentage increase was significantly smaller in ADAMTS5-/- mice (WT: 20.7+/-4.7%, ADAMTS5-/-: 8.3+/-1.2% compared to the left unoperated control joint). In ADAMTS5-/- animals a significant decrease was found in both Oc.N./BS and Oc.S./BS. Finally, in WT but not in ADAMTS5-/- mice a significant correlation was found between medial subchondral bone plate thickness and cartilage damage at the medial tibial plateau. CONCLUSION: ADAMTS5-/- joints that were protected from cartilage damage showed minor changes in the subchondral bone structure, in contrast to WT mice where substantial changes were found. This finding suggests links between the process of cartilage damage and subchondral bone changes in instability-induced OA.

The high osmolarity glycerol response (HOG) MAP kinase pathway controls localization of a yeast golgi glycosyltransferase.

The yeast alpha-1,3-mannosyltransferase (Mnn1p) is localized to the Golgi by independent transmembrane and lumenal domain signals. The lumenal domain is localized to the Golgi complex when expressed as a soluble form (Mnn1-s) by exchange of its transmembrane domain for a cleavable signal sequence (Graham, T. R., and V. A. Krasnov. 1995. Mol. Biol. Cell. 6:809-824). Mutants that failed to retain the lumenal domain in the Golgi complex, called lumenal domain retention (ldr) mutants, were isolated by screening mutagenized yeast colonies for those that secreted Mnn1-s. Two genes were identified by this screen, HOG1, a gene encoding a mitogen-activated protein kinase (MAPK) that functions in the high osmolarity glycerol (HOG) pathway, and LDR1. We have found that basal signaling through the HOG pathway is required to localize Mnn1-s to the Golgi in standard osmotic conditions. Mutations in HOG1 and LDR1 also perturb localization of intact Mnn1p, resulting in its loss from early Golgi compartments and a concomitant increase of Mnn1p in later Golgi compartments.

The addition of cottonseed hulls to the starter and supplementation of live yeast or mannanoligosaccharide in the milk for young calves.

The objectives of this study were to investigate the effects of the addition of cottonseed hulls (CSH) to the starter and the supplementation of live yeast product (YST) or mannanoligosaccharide product (MOS) to milk, on growth, intake, rumen development, and health parameters in young calves. Holstein (n = 116) and Jersey (n = 46) bull (n = 74) and heifer (n = 88) calves were assigned randomly within sex at birth to treatments. All calves were fed 3.8 L of colostrum daily for the first 2 d. Holstein calves were fed 3.8 L of whole milk, and Jersey calves were fed 2.8 L of whole milk through weaning at 42 d. Calves continued on trial through 63 d. Six treatments were arranged as a 2 x 3 factorial. Calves received either a corn-soybean meal-based starter (21% crude protein and 6% acid detergent fiber; -CSH) or a blend of 85% corn-soybean meal-based starter and 15% CSH (18% crude protein and 14% acid detergent fiber; +CSH) ad libitum. In addition, calves received whole milk with either no supplement (NONE) or supplemented with 3 g/d of mannanoligosaccharide product (MOS) or 4 g/d of live yeast product (YST) through weaning at 42 d. Twelve Holstein steers [n = 6 (per starter type); n = 4 (per supplement type)] were euthanized for collection and examination of rumen tissue samples. Dry matter intake (DMI) was greater for Holstein calves fed +CSH (0.90 kg/d) than -CSH (0.76 kg/d). Final body weight at 63 d of Holstein calves fed +CSH (75.8 kg) was greater than that of those fed -CSH (71.0 kg). Average daily gain (ADG) was greater for Holstein calves fed +CSH (0.58 kg/d) than -CSH (0.52 kg/d). However, Holstein calves fed -CSH had a greater feed efficiency (FE; 0.71 kg of ADG/kg of DMI) than those fed +CSH (0.65 kg of ADG/kg of DMI). Also, Holstein calves fed +CSH had narrower rumen papillae (0.32 mm) compared with those fed -CSH (0.41 mm). There were no significant effects of CSH on DMI, ADG, or FE in Jersey calves. There were no significant effects of YST or MOS on DMI, ADG, FE, or rumen papillae measures in Holstein calves. Jersey calves fed YST or MOS had greater final body weight at 63 d (51.2 kg and 51.0 kg, respectively) than calves fed NONE (47.5 kg). However, there were no significant effects of YST or MOS on DMI, ADG, or FE in Jersey calves.

Supplementing limited methionine diets with rumen-protected methionine, betaine, and choline in early lactation Holstein cows.

Eighty lactating Holstein cows from 21 to 91 d in milk were fed a corn silage-based total mixed ration (TMR) formulated with the Met content limited (42 g/ d) to investigate the impact of supplementing rumen-protected (RP) forms of Met, betaine, and choline on performance and metabolism. One of 4 supplements was blended into the TMR to produce 4 dietary treatments: 1) control, 2) 20 g/d of RP-Met, 3) 45 g/d of RP-betaine, and 4) 40 g/d of RP-choline. Calcium salts of fatty acids were used to protect both RP-betaine and RP-choline supplements. A similar amount of Ca salts of fatty acids was included in both control and RP-Met supplements to provide equal amounts of fat to all treatments. Overall, no differences in intake, milk yield, or milk composition were observed in primiparous cows. Average dry matter intake, body weight, and body condition score were not different among treatments in multiparous cows. Milk yield was higher in multiparous cows fed RP-choline compared with the other treatments. Multiparous cows fed RP-choline had higher milk protein yield than cows fed control or RP-betaine but was not different from cows fed RP-Met. Multiparous cows fed RP-choline had higher milk fat yield than cows fed RP-Met but was not different from cows fed control or RP-betaine. There were no beneficial effects of RP-betaine supplementation to a Met-limited TMR.

Digitalis-induced increase in aortic regurgitation and the contrasting effect of glucagon in the sedated dog.

The hemodynamic and phasic ascending aortic flow changes induced by acetylstrophanthidin and glucagon were studied in closed-chest sedated dogs with aortic regurgitation. While the positive inotropic effect of both agents was reflected in an increase in peak rate of rise of left ventricular pressure, acetylstrophanthidin increased aortic regurgitation, while glucagon decreased it. With the former, left ventricular end-diastolic pressure rose from 20+/-6 to 27+/-6 mm Hg (P < 0.005), but fell from 18+/-4 to 11+/-3 mm Hg (P < 0.001) with glucagon. Acetylstrophanthidin increased systemic vascular resistance, aortic diastolic pressure, and diastolic regurgitant flow rate, and, heart rate and the duration of regurgitation per beat and per minute being unchanged, regurgitant flow per beat increased 32+/-15% (P < 0.001). Glucagon decreased regurgitant flow per beat 27+/-14% (P < 0.001) because of abbreviation of diastole associated with tachycardia, and because of reduction in regurgitant flow rate. Despite tachycardia, the duration of regurgitation per minute was unchanged, and the small fall in regurgitant blood flow per minute was not significant, but this pertained in the face of 47% increase in effective cardiac output (P < 0.001). In contrast, acetylstrophanthidin increased regurgitant flow per minute 28+/-14% (P < 0.001) without change in effective cardiac output. The increase in cardiac contractility, tachycardia, and systemic vasodilatation induced by glucagon preferentially enhanced forward blood flow, which led to reduction in left ventricular volume overload, while it increased cardiac output. Contrarily, acetylstrophanthidin increased aortic regurgitation and, despite its inotropic effect, increased left ventricular volume overload without an increase in cardiac output.

Lactoferrin supplementation to Holstein calves during the preweaning and postweaning phases.

Sixty Holstein calves (30 bulls, 30 heifers) were used to examine the effects of supplemental lactoferrin on feed intake, growth, and health during the preweaning and postweaning periods. One of 3 levels of lactoferrin was supplemented from 3 to 56 d in either whole milk or water to produce 3 dietary treatments: 1) 0 g/d, 2) 0.5 g/d, and 3) 1 g/d. Whole milk (3.8 L/d) containing lactoferrin supplements was fed from bottles until weaning at 35 d. From d 36 to 56, lactoferrin supplements were added to water (15 to 25 mL) and fed from bottles. Lactoferrin supplementation had no effect on feed intake, body weight, average daily gain, heart girth, body temperature, fecal scores, respiratory scores, or haptoglobin concentrations. Calves were housed in individual pens in either an open-sided barn or hutches. Calves raised in the barn consumed more calf starter and therefore grew better than calves raised in hutches. Under the conditions of this study, lactoferrin supplementation was not beneficial. Further research is needed to fully elucidate the role of lactoferrin, and possible benefits during different feeding conditions or milk sources.

Percutaneous coronary laser balloon angioplasty: initial results of a multicenter experience.

A multicenter clinical trial was initiated to test the potential safety and short-term efficacy of a percutaneous coronary application of laser balloon angioplasty, which has been shown experimentally to alleviate the common causes (dissection, recoil, thrombus) of suboptimal luminal results of conventional balloon angioplasty. Fifty-five patients, the majority (62%) of whom had relatively high risk lesions, were treated in 10 centers with a laser balloon that was identical in size (3 x 20 mm) to a balloon used for conventional balloon angioplasty performed on the same lesion immediately before laser balloon angioplasty. One or more neodymium:yttrium aluminum garnet (Nd:YAG) (1,060 nm) laser doses of 250 to 450 J were each delivered over a 20 s duration per exposure. Immediately and 1 day after laser balloon angioplasty no significant adverse effects on the arterial lumen were noted in any patient. By computerized image analysis of cineangiograms initial conventional balloon angioplasty failed to achieve a minimal luminal diameter greater than 1.5 mm in 14 patients (25%), including 3 patients with acute closure. However, after subsequent laser balloon angioplasty, minimal luminal diameter exceeded this value in all patients including this subgroup. Overall, minimal luminal diameter increased from 1.74 +/- 0.46 mm after conventional balloon angioplasty to 2.32 +/- 0.31 mm after laser balloon angioplasty (p less than 0.001) with no change found on 1 day and 1 month follow-up angiograms. Thus, laser balloon angioplasty is a safe, effective procedure for improving luminal dimensions after conventional balloon angioplasty.

Repeated low-level formaldehyde exposure produces cross-sensitization to cocaine: possible relevance to chemical sensitivity in humans.

Sensitivity to chemicals in humans has been proposed to be an acquired disorder in which individuals become increasingly sensitive to chemicals in the environment. A possible link between the manifestation of psychiatric symptoms in individuals claiming sensitivity to chemicals was investigated based on a leading hypothesis put forth by Bell and co-workers (1992) to explain the amplification of symptoms after chemical exposure. The hypothesis is that chemical sensitivities may be akin to sensitization observed in rodents after repeated psychostimulants. Repeated exposure to psychostimulants enhances behavioral activity and the underlying neurochemical responses in specific limbic pathways; a similar sensitization of limbic pathways has been proposed to occur in individuals who become sensitive to chemicals. To test this hypothesis, female Sprague-Dawley rats were exposed to either air or formaldehyde (Form) for 1 h/day for 7 days or 20 days (5 days/week x 4 weeks). Two to 4 days after the last exposure, rats were given a cocaine challenge (= early withdrawal) followed by an additional cocaine challenge 4-6 weeks later (= late withdrawal). No differences in cocaine-induced locomotor activity were noted between groups after 7 days of exposure. However, after 20 days of exposure to Form, vertical activity was significantly elevated at both early and late withdrawal times. These studies demonstrate that behavioral sensitization occurs after long-term, but not short-term, low-level exposure to Form, and lends support to the limbic system sensitization hypothesis of sensitivity to chemicals in humans.

Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors.

The affinity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1H-indole) for a range of 5-HT receptors was compared to values obtained for other 5-HT1B/1D receptor agonists known to be effective in the treatment of migraine. Eletriptan, like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity for the human 5-HT1B, 5-HT1D and putative 5-ht1f receptor. Kinetic studies comparing the binding of [3H]eletriptan and [3H]sumatriptan to the human recombinant 5-HT1B and 5-HT1D receptors expressed in HeLa cells revealed that both radioligands bound with high specificity (>90%) and reached equilibrium within 10-15 min. However, [3H]eletriptan had over 6-fold higher affinity than [3H]sumatriptan at the 5-HT1D receptor (K(D)): 0.92 and 6.58 nM, respectively) and over 3-fold higher affinity than [3H]sumatriptan at the 5-HT1B receptor (K(D): 3.14 and 11.07 nM, respectively). Association and dissociation rates for both radioligands could only be accurately determined at the 5-HT1D receptor and then only at 4 degrees C. At this temperature, [3H]eletriptan had a significantly (P<0.05) faster association rate (K(on) 0.249 min(-1) nM(-1)) than [3H]sumatriptan (K(on) 0.024 min(-1) nM(-1)) and a significantly (P<0.05) slower off-rate (K(off) 0.027 min(-1) compared to 0.037 min(-1) for [3H]sumatriptan). These data indicate that eletriptan is a potent ligand at the human 5-HT1B, 5-HT1D, and 5-ht1f receptors and are consistent with its potent vasoconstrictor activity and use as a drug for the acute treatment of migraine headache.

Enzyme and biochemical studies of stonefish (Synanceja trachynis) and soldierfish (Gymnapistes marmoratus) venoms.

Venoms from the scorpaeniformes Synanceja trachynis and Gymnapistes marmoratus were quantitatively analyzed for enzymic activity. S. trachynis venom displayed significantly higher hyaluronidase activity than G. marmoratus venom, and G. marmoratus venom displayed significantly higher levels of esterase, acid phosphatase, alkaline phosphatase and phosphodiesterase activity. No detectable quantities of phospholipase A2 activity were found in G. marmoratus venom. SDS-polyacrylamide gel electrophoresis of S. trachynis venom indicated the presence of 6 protein bands (20 kDa-295 kDa). G. marmoratus venom displayed 8 protein bands (11 kDa-109 kDa).