Deep inspirations attenuate postprandial airway inflammation in college-aged adults with elevated baseline exhaled nitric oxide: A pilot study.

Airway inflammation (assessed by exhaled nitric oxide (eNO)) increases after a single high-fat meal (HFM), yet this response may be modified by airway stretch and baseline eNO level.Purpose: The purpose of this study was to investigate whether deep inspirations (DIs) would attenuate airway inflammation post-HFM and whether this is modulated by baseline eNO level.Methods: A total of sixteen healthy college-aged participants completed a randomized cross-over study with 8 lower eNO (14.8 ± 2.0 ppb: 3 M/5F; age: 22.0 ± 2.2 yrs) and 8 higher eNO (29.3 ± 11.6 ppb 5 M/3F; age: 22.5 ± 2.6 yrs) participants. All participants completed a control (CON) condition (no DIs pre-HFM) and DI condition (60 DI's to total lung capacity immediately pre-HFM) after an overnight fast. The primary outcome was eNO. Participants had 20 minutes to consume the HFM (1 g fat/1 kg body weight) and eNO was performed at 2- and 4- hours post-HFM. To determine whether baseline eNO levels impacted the effect of DI's, a median split was performed on their baseline eNO level.Results: There was a significant increase in eNO as a main effect of time (p < 0.001). However when analyzing the potential effect of baseline eNO, there was no significant increase in eNO post-HFM in the higher eNO group in the DI condition (p = 0.54). DIs modified the eNO response to a HFM in the group with a higher baseline eNO value.Conclusions: These data display a possible bronchoprotective protect of DIs against postprandial airway inflammation in participants with higher initial eNO level.

Ketoprofen pharmacokinetics of R- and S-isomers in juvenile loggerhead sea turtles (Caretta caretta) after single intravenous and single- and multidose intramuscular administration.

Ketoprofen is a nonsteroidal anti-inflammatory and analgesic agent that nonselectively inhibits cyclooxygenase, with both COX-1 and COX-2 inhibition. Recent studies on COX receptor expression in reptiles suggest that nonselective COX inhibitors may be more appropriate than more selective inhibitors in some reptiles, but few pharmacokinetic studies are available. The goal of this study was to determine single- and multidose (three consecutive days) pharmacokinetics of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg in healthy juvenile loggerhead turtles (Caretta caretta). The S-isomer is the predominant isomer in loggerhead sea turtles, similar to most mammals, despite administration of a 50:50 racemic mixture. Multidose ketoprofen administration demonstrated no bioaccumulation; therefore, once-daily dosing will not require dose adjustment over time. S-isomer pharmacokinetic parameters determined in this study were Cmax of 10.1 µg/ml by IM injection, C0 of 13.4 µg/ml by IV injection, AUC of 44.7 or 69.4 µg*hr/ml by IM or IV injection, respectively, and T½ of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen plasma concentrations were maintained for at least 12 hr above concentrations determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV every 24 hr is likely appropriate for loggerhead turtles.

Post-prandial systemic 8-isoprostane increases after consumption of moderate and high-fat meals in insufficiently active males.

A single high-fat meal (HFM) leads to an increase in triglycerides and oxidative stress. Oxidative stress can be assessed via 8-isoprostane generation, which is associated with the development of asthma and cardiovascular disease. No previous research has investigated whether airway and systemic 8-isoprostane increases postprandially in nonasthmatic participants according to the energy and fat content of a meal. Our purpose was to assess airway and systemic 8-isoprostane after a HFM and a true-to-life moderate-fat meal (MFM). We hypothesized that airway and systemic 8-isoprostane would increase after a HFM and a MFM, with the greatest increase in the HFM condition. Eight nonasthmatic men (25.8±6.9years) completed the HFM and MFM trials in a randomized crossover design. After a 10-hour fast, participants consumed either a HFM (71.13kJ/kg body mass, 60% fat, 23% CHO) or a MFM (35.56kJ/kg body mass, 30% fat, 52% CHO). Exhaled breath condensate to assess airway 8-isoprostane was collected at baseline and at 3 and 6hours postmeal. Venous blood samples were collected at baseline and hourly until 6hours postmeal to assess triglycerides, and every 3hours for systemic 8-isoprostane. Airway 8-isoprostane responses were not significant as a main effect of time (P=.072), between conditions (P=.365), or between time and condition (P=.319) postmeal. Systemic 8-isoprostane increased over time (P<.001), but not between conditions (P=.124) or between time and condition (P=.649) postmeal. Triglyceride incremental area under the curve was different in the HFM compared to the MFM condition (P=.013). After a HFM and a MFM, 8-isoprostane increases systemically; however, airway 8-isoprostane does not change.

High-intensity functional training improves functional movement and body composition among cancer survivors: a pilot study.

This pilot study investigated feasibility and preliminary efficacy of a high-intensity functional training (HIFT) group-exercise programme among adult cancer survivors within 5 years of last cancer treatment. Eight participants were assigned to a 5-week, 3 days/week HIFT intervention with four testing sessions and 12 workouts along with mobility and stretching exercises. Feasibility was assessed by initiation, adherence, and acceptability. Efficacy was determined by changes from baseline to post-test in health-related quality of life, body composition and functional movement. The recruitment rate was 80% and the adherence rate was 75%. Significant improvements were found for emotional functioning (P = 0.042) and body composition (lean mass +3.8 ± 2.1 kg, P = 0.008; fat mass -3.3 ± 1.0 kg, P = 0.001; body fat percentage -4.7 ± 1.2%, P < 0.001). Participants also significantly improved on five of seven functional movements: balance (P = 0.032), carrying a weighted object (P = 0.004), lower body strength and power (P = 0.009), aerobic capacity and endurance (P = 0.039), and perceived difficulty for flexibility (P = 0.012). Five weeks of HIFT training was well-received and feasible for most cancer survivors, and effective for improving emotional functioning, body composition and functional movement.

Meloxicam pharmacokinetics using nonlinear mixed-effects modeling in ferrets after single subcutaneous administration.

This study was designed to investigate the pharmacokinetics of meloxicam, an oxicam class, nonsteroidal anti-inflammatory drug (NSAID), in ferrets. We determined the pharmacokinetic properties of a single subcutaneous dose of meloxicam (0.2 mg/kg) in nine male and nine female ferrets. Blood samples were collected by venipuncture of the cranial vena cava into heparinized syringes. Plasma meloxicam concentrations were determined by high-pressure liquid chromatography (HPLC). Pharmacokinetic variables were calculated using nonlinear mixed-effects modeling to take advantage of the population-based sampling scheme and to minimize sample volume collected per animal. Maximum plasma concentration, volume of distribution per absorption, and elimination half-life were 0.663 µg/mL, 0.21 L, and 11.4 h, respectively, for females and 0.920 µg/mL, 0.35 L, and 17.8 h, respectively, for males. Significant differences were found in each of the above parameters between male and female ferrets. Systemic clearance per absorption was not affected by gender and was 13.4 mL/h. Analgesic efficacy was not evaluated, but plasma meloxicam concentrations achieved in these animals are considered effective in other species. Sex differences in the pharmacokinetic behavior of meloxicam should be taken into consideration when treating ferrets.

The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal.

INTRODUCTION: Many environmental and dietary influences can cause immune cells to produce biological mediators that increase airway inflammation. A high-fat meal (HFM) is one stimulus that increases airway inflammation in healthy individuals. Supplementation with omega-3 fatty acids can reduce inflammation systemically and may be beneficial to the airways. PURPOSE: To determine if omega-3 fatty acid supplementation via fish oil would mitigate the airway inflammatory response induced by a single HFM. METHODS: Seventeen non-asthmatic men (22 ± 2 years.) were supplemented with 3,000 mg × day(-1) fish oil or a placebo for 3 weeks. Fractional exhaled nitric oxide (FENO; a marker of airway inflammation), impulse oscillometry (a measure of respiratory impedance), pulmonary function, and triglycerides were measured prior to and 2 h following a HFM. RESULTS: Following a HFM, triglycerides increased in both fish oil and placebo groups compared to pre-HFM (~59 and ~49 %, respectively, p < 0.05). The percent increase in FENO was greater in the placebo group compared to the fish oil group (25.7 ± 16.7 vs. -1.99 ± 10.5 %, respectively, p < 0.05). A significant correlation was observed between blood triglycerides and FENO in the placebo group (r = 0.61; p < 0.05), but not the fish oil group (p = 0.21). CONCLUSION: A single HFM increases airway inflammation and omega-3 fatty acid supplementation via fish oil protects against HFM associated changes in airway health.

A single test for the determination of parameters of the speed-time relationship for running.

A validated expeditious method is needed to determine critical speed (CS) and the finite distance that can be covered above CS (D'). We tested the hypothesis that a single all-out 3-min running test would accurately determine CS and D'. Seven healthy subjects completed three constant-speed runs on a treadmill for the determination of CS and D', as well as an all-out 3-min test on a track for the determination of end-test speed (ES) and the distance above end-test speed (DES). ES (13.4 ± 2.8 km h(-1)) was not significantly different from the speed-1/time model CS (13.3 ± 2.8 km h(-1)). While DES (141 ± 34 m) was not significantly different from D' (204 ± 103 m), it underestimated D' in 5 of 7 subjects. Thus, the speed-1/time model CS can be accurately determined using a single 3-min test, while caution should be used in relating DES to D'.

Rapid decreases in salinity, but not increases, lead to immune dysregulation in Nile tilapia, Oreochromis niloticus (L.).

Rapid changes in salinity, as with other environmental stressors, can have detrimental effects on fish and may trigger increased susceptibility to disease. However, the precise mechanisms of these effects are not well understood. We examined the effects of sudden increases or decreases in salinity on teleost immune function using Nile tilapia, Oreochromis niloticus (L.), as the fish model in a battery of bioassays of increasing immune system specificity. Two different salinity experiments were performed: one of increasing salinity (0 to 5, 10 and 20 g L(-1) ) and one of decreasing salinity (20 to 15, 10 and 5 g L(-1) ). Histopathology of anterior kidney, gills, gonads, intestines and liver of exposed fish was performed, but no remarkable lesions were found that were attributable to the salinity treatment regimes. The spleen was removed from each fish for analysis of cytokine expression, and peripheral blood was used for haematology, cortisol and phagocytosis assays. In the increasing salinity experiments, no significant changes were observed in any immune system assays. However, in the decreasing salinity experiments, lymphopenia, neutrophilia and monocytosis were observed in the peripheral blood without modification of the packed cell volume, plasma protein or plasma cortisol levels. Phagocytosis was increased in response to decreases in salinity from 20 g L(-1) to 15 g L(-1) , 10 g L(-1) and 5 g L(-1) , whereas phagocytic index was not significantly altered. Transforming growth factor-ß (TGF-ß) transcription increased during the same decreases in salinity. However, the TGF-ß value at 5 g L(-1) was less than those in the 15 and 10 g L(-1) salinity treatments. Interleukin-1ß (IL-1ß) transcription did not significantly respond to either salinity regime. In total, acute salinity changes appeared to trigger reactive dysregulation of the immune response in tilapia, a situation which, when combined with additional co-occurring stressors such as sudden changes in temperature and/or dissolved oxygen, could make fish more susceptible to infectious diseases. Accordingly, these findings may help to explain how sudden environmental changes may initiate disease outbreaks and lead to critical declines in cultured or wild fish populations.

Hematology, plasma biochemistry, and tissue enzyme activities of invasive red lionfish captured off North Carolina, USA.

The red lionfish Pterois volitans is important not only in the aquarium trade but also as an invasive species in the western Atlantic. Introduced to waters off the southeastern coast of the United States, red lionfish have rapidly spread along much of the East Coast and throughout Bermuda, the Bahamas, and much of the Caribbean. Hematology and plasma biochemistry were evaluated in red lionfish captured from the offshore waters of North Carolina to establish baseline parameters for individual and population health assessment. Blood smears were evaluated for total and differential white blood cell counts, and routine clinical biochemical profiles were performed on plasma samples. To improve the interpretive value of routine plasma biochemistry profiles, tissue enzyme activities (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], lactate dehydrogenase [LD], and creatine kinase [CK]) were analyzed from liver, kidney, skeletal muscle, gastrointestinal tract, and heart tissues from five fish. The hematological and plasma biochemical values were similar to those of other marine teleosts except that the estimated white blood cell counts were much lower than those routinely found in many species. The tissue enzyme activity findings suggest that plasma LD, CK, and AST offer clinical relevance in the assessment of red lionfish.

Field anaesthesia of leatherback sea turtles (Dermochelys coriacea).

Ten nesting leatherback sea turtles on Trinidad were anaesthetised for electroretinogram (ERG) measurements, using ketamine and medetomidine, reversed with atipamezole. They weighed 242 to 324 kg and were given initial doses of 3 to 8 mg/kg ketamine and 30 to 80 microg/kg medetomidine administered into an external jugular vein; six of the turtles received supplementary doses of 2.6 to 3.9 mg/kg ketamine combined with 0 to 39 microg/kg medetomidine. The lower doses were used initially to ensure against overdosage and reduce the chances of residual effects after the turtles returned to the water, but successful ergs called for step-wise dose increases to the required level of anaesthesia. Respiratory rate, heart rate, electrocardiogram, cloacal temperature, and venous blood gases were monitored, and blood was collected for plasma biochemistry. At the end of the erg procedure, atipamezole was administered at 150 to 420 microg/kg (five times the dose of medetomidine), half intramuscularly and half intravascularly. The turtles were monitored and prevented from re-entering the water until their behaviour was normal. No apparent mortalities or serious anaesthetic complications occurred. The observed within-season return nesting rate of the anaesthetised turtles was comparable with that of unanaesthetised turtles.

The identification of a genetically unique piroplasma in North American river otters (Lontra canadensis).

During a routine health check of a wild-caught North American river otter (Lontra canadensis) small piroplasms were noted within erythrocytes. Analyses of the 18S ribosomal ribonucleic acid (rRNA) gene sequences determined that this was a genetically unique organism most closely related to Babesia microti-like parasites found in other small carnivores. Subsequently 39 wild-trapped North American river otters from North Carolina were tested for the presence of piroplasma deoxyribonucleic acid (DNA) via polymerase chain reaction and piroplasma DNA was detected in 82% (32/39) of these samples. Sequencing of partial 18S rRNA genes from selected cases determined that they were identical to the sentinel case. This report documents the existence of a genetically unique piroplasma in North American river otters and indicates that the prevalence of piroplasma in North Carolina otters is quite high. The pathogenic potential of this organism for otters or other species remains unknown.

Acute hypoxia-reperfusion triggers immunocompromise in Nile tilapia.

Inadequate dissolved oxygen in the aquatic environment is a well-established cause of fish morbidity and mortality. The specific effects of hypoxia on immune function in fish, however, are not well characterized. In this study, the effects of acute hypoxia followed by reoxygenation (rapid tissue reperfusion) as a source of immunocompromise in Nile tilapia Oreochromis niloticus were investigated. Using a precision apparatus developed in our laboratory for hypoxia exposures, a series of assays of increasing specificity for immune function were performed on acutely hypoxia-stressed Nile tilapia: tier I consisted of histopathology, tier II of hematology, plasma chemistry, and determining cortisol concentration, and tier III of determining the phagocytic index and analyzing the expression of the cytokines transforming growth factor-beta (TGF-beta) and interleukin-1beta (IL-1beta). Nile tilapia were exposed to 7% oxygen saturation for 96 h, then tank water was rapidly reoxygenated. Sampling intervals were 48 and 96 h during hypoxia and 12 and 84 h during reperfusion. Histopathology showed no remarkable microscopic abnormalities in lymphoid or other tissues. Lymphopenia and neutrophilia were observed in peripheral blood. Plasma total protein, partial pressure of oxygen, and oxygen saturation were decreased in response to hypoxia. Plasma lipase decreased in response to hypoxia but returned to normal during reperfusion. Phagocytic capability and the phagocytic index decreased during hypoxia and 12 h reperfusion, whereas these values were recovered by 84 h reperfusion. The TGF-beta transcription continued to increase during the exposures, the greatest production being at 12 h reperfusion, whereas IL-1beta transcription decreased in response to hypoxia and reperfusion. We conclude that acute hypoxia triggered an overall downregulation of the immune system in the test fish. This suggests a possible factor in the pathogenesis of disease outbreaks in fish in which repeated, sublethal bouts of environmentally induced hypoxia lead to increased disease susceptibility and individual mortalities rather than massive fish kills.

Multitiered health assessment of Atlantic menhaden in the Pamlico River, North Carolina.

During the fall of 2001 and 2002, Atlantic menhaden Brevoortia tyrannus were collected from several creeks in the Pamlico River, North Carolina, to investigate recent fish kills and ulcerative skin lesions. High skin lesion prevalence (>50%) was associated with the Atlantic menhaden kills in fall 2001, whereas there were no fish kills in fall 2002 and skin lesion prevalence was lower (< or =50%). Indicators of tissue damage (histopathological analyses of gills, heart, liver, intestine, and anterior kidney), body condition (liver somatic index), and immune status (transforming growth factor-beta [TGF-beta] messenger RNA [mRNA] production, hematology, plasma chemistry, and splenosomatic index) were compared between Atlantic menhaden with and without ulcerative skin lesions in fall. Atlantic menhaden with ulcerative skin lesions had significantly higher liver somatic indices, neutrophil and monocyte percentages, and splenic mononuclear cell TGF-beta mRNA levels than did fish without lesions. Hematocrit values, plasma protein, and Ca concentrations were significantly lower in fish with ulcerative skin lesions than in those without. The indicators used in this study at multiple levels of biological organization have provided valuable baseline data for understanding the health status of lesioned and nonlesioned Atlantic menhaden in the Pamlico River.

A quantitative real-time RT-PCR assay to measure TGF-beta mRNA and its correlation with hematologic, plasma chemistry and organo-somatic indices responses in triamcinolone-treated Atlantic menhaden, Brevoortia tyrannus.

A quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assay was developed to measure transforming growth factor-beta (TGF-beta) in Atlantic menhaden (Brevoortia tyrannus), an estuarine-dependent species plagued by ulcerative skin lesions in the estuaries along the eastern United States. Atlantic menhaden were acclimated in a closed system for two weeks prior to initiation of the study. The synthetic glucocorticoid, triamcinolone acetonide (10mg/kg body weight) was administered by intracoelomic injection and its effect on the splenic mononuclear cell TGF-beta mRNA transcription, liver-somatic index, spleno-somatic index, hematology, and plasma chemistry were compared to untreated fish at 48 and 96h post-treatment. Triamcinolone-treated Atlantic menhaden showed suppression of TGF-beta mRNA production, neutrophilia, monocytosis, lymphopenia, and an increase in blood glucose concentrations. The health indices used in this study may help us interpret some of the changes observed during the development of ulcerative skin lesions in wild-caught menhaden.

Enrofloxacin pharmacokinetics in the European cuttlefish, Sepia officinalis, after a single i.v. injection and bath administration.

Enrofloxacin pharmacokinetics were studied in European cuttlefish, Sepia officinalis, after a single 5 mg/kg i.v. injection or a 2.5 mg/L 5 h bath. A pilot study with two animals was also performed following a 10 mg/kg p.o. administration. The concentration of enrofloxacin in hemolymph was assayed using high-performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived from compartmental methods. In the i.v. study, the terminal half-life (t(1/2)), apparent volume of distribution, and systemic clearance were respectively 1.81 h, 385 mL/kg, and 4.71 mL/min/kg. Following bath administration the t(1/2), peak hemolymph concentration (C(max)), and area under the curve to infinity (AUC(0-infinity)) were 1.01 h, 0.5 +/- 0.12 mug/mL, and 0.98 microg.h/mL, respectively. After oral administration, the t(1/2), C(max), and AUC(0-infinity) were 1.01 h, 10.95 microg/mL, 26.71 mug.h/mL, respectively. The active metabolite of enrofloxacin, ciprofloxacin, was not detected in any samples tested. The hemolymph concentration was still above minimum inhibitory concentration (MIC) values for shrimp and fish bacterial isolates at 6 h after i.v. administration, therefore, a dose of 5 mg/kg i.v. every 8-12 h is suggested for additional studies of efficacy. The C(max) value for the water bath was lower than for the i.v. study, but a bath of 2.5 mg/L for 5 h once to twice daily is suggested for additional studies to test efficacy against highly susceptible organisms. Although only two animals were used for the oral study, a dose of 10 mg/kg produced hemolymph concentrations of enrofloxacin that were in a range consistent with therapeutic efficacy in other species.