Eprinomectin in dairy zebu Gobra cattle (Bos indicus): plasma kinetics and excretion in milk

The pharmacokinetics and mammary excretion of eprinomectin were determined in zebu Gobra following topical administration of 0.5 mg kg⁻¹. The kinetics of plasma and milk was analysed using a one-compartment model. The maximum plasma concentration of 8.83±2.15 ng ml⁻¹ occurred 1.30 days post-administration. The area under the plasma concentration–time curve was 30.63±5.56 ng day⁻¹ ml⁻¹ and the mean residence time was 3.38±0.60 days. Eprinomectin was detected in milk at the first sampling time and thereafter for at least 8 days. The systemic availability of eprinomectin was significantly lower than that for other breeds of cattle. Comparison of the milk and plasma data demonstrated the parallel disposition of the drug in the milk and plasma with a milk/plasma ratio of 0.094. The very low extent of mammary excretion supports the permitted use of eprinomectin in lactating zebu Gobra.     

Simulated moderate altitude elevates serum erythropoietin but does not increase reticulocyte production in well-trained runners

The purpose of this study was to investigate whether the modest increases in serum erythropoietin (sEpo) experienced after brief sojourns at simulated altitude are sufficient to stimulate reticulocyte production. Six well-trained middle-distance runners (HIGH, mean maximum oxygen uptake, V˙O_2max = 70.2 ml · kg⁻¹ · min⁻¹) spent 8–11 h per night for 5 nights in a nitrogen house that simulated an altitude of 2650 m. Five squad members (CONTROL, mean V˙O_2max = 68.9 ml · kg⁻¹ · min⁻¹) undertook the same training, which was conducted under near-sea-level conditions (600 m altitude), and slept in dormitory-style accommodation also at 600 m altitude. For both groups, this 5-night protocol was undertaken on three occasions, with a 3-night interim between successive exposures. Venous blood samples were measured for sEpo after 1 and 5 nights of hypoxia on each occasion. The percentage of reticulocytes was measured, along with a range of reticulocyte parameters that are sensitive to changes in erythropoiesis. Mean serum erythropoietin levels increased significantly (P < 0.01) above baseline values [mean (SD) 7.9 (2.4) mU · ml⁻¹] in the HIGH group after the 1st night [11.8 (1.9) mU · ml⁻¹, 57%], and were also higher on the 5th night [10.7 (2.2) mU · ml⁻¹, 42%] compared with the CONTROL group, whose erythropoietin levels did not change. After athletes spent 3 nights at near sea level, the change in sEpo during subsequent hypoxic exposures was markedly attenuated (13% and −4% change during the second exposure; 26% and 14% change during the third exposure; 1st and 5th nights of each block, respectively). The increase in sEpo was insufficient to stimulate reticulocyte production at any time point. We conclude that when daily training loads are controlled, the modest increases in sEpo known to occur following brief exposure to a simulated altitude of 2650 m are insufficient to stimulate reticulocyte production. Accepted: 7 October 1999     

Involvement of muscarinic cholinergic and α2-adrenergic mechanisms in growth hormone secretion during exercise in humans

The purpose of this study was to examine the role of muscarinic cholinergic and α₂-adrenergic mechanisms in growth hormone (GH) secretion during exercise in humans. The GH responses induced during moderate-intensity exercise (using a cycle ergometer at 60% maximal oxygen uptake, V˙O_2max, for 30 min) without treatment (control) and after the administration of a muscarinic cholinergic antagonist (atropine 1 mg) or after an α₂-adrenergic antagonist (yohimbine 15 mg) were compared in seven healthy men. Although, serum GH concentration had increased significantly after exercise in the control experiment [mean peak GH concentration 52.64 (SEM 18.60) ng · ml⁻¹], the increase was suppressed by the administration of either atropine [mean peak GH concentration 8.64 (SEM 7.47)  ng · ml⁻¹] or yohimbine [mean peak GH concentration 17.50 (SEM 7.89) ng · ml⁻¹]. The area under the curve of serum GH concentration against time was significantly lower in the experiment using these drugs [with atropine, mean area 458 (SEM 409) ng · ml⁻¹ · min], with yohimbine mean area 946 (SEM 435) ng · ml⁻¹ · min] than in the control experiment [mean area 3135 (SEM 1098) ng · ml⁻¹ · min]. These results suggest that muscarinic cholinergic and α₂-adrenergic mechanisms are involved in GH secretion during exercise in humans. Accepted: 9 March 2000     

The influence of either no fluid or carbohydrate-electrolyte fluid ingestion and the environment (thermoneutral versus hot and humid) on running economy after prolonged, high-intensity exercise

This study investigated the effects on running economy (RE) of ingesting either no fluid or an electrolyte solution with or without 6% carbohydrate (counterbalanced design) during 60-min running bouts at 80% maximal oxygen consumption (V˙O_2max). Tests were undertaken in either a thermoneutral (22–23°C; 56–62% relative humidity, RH) or a hot and humid natural environment (Singapore: 25–35°C; 66–77% RH). The subjects were 15 young adult male Singaporeans [V˙O_2max = 55.5 (4.4 SD) ml kg⁻¹ min⁻¹]. The RE was measured at 3 m s⁻¹ [65 (6)% V˙O_2max] before (RE1) and after each prolonged run (RE2). Fluids were administered every 2 min, at an individual rate determined from prior tests, to maintain body mass (group mean = 17.4 ml min⁻¹). The V˙O₂ during RE2 was higher (P < 0.05) than that during the RE1 test for all treatments, with no differences between treatments (ANOVA). The mean increase in V˙O₂ from RE1 to RE2 ranged from 3.4 to 4.7 ml kg⁻¹ min⁻¹ across treatments. In conclusion, the deterioration in RE at 3 m s⁻¹ (65% V˙O_2max) after 60 min of running at 80% V˙O_2max appears to occur independently of whether fluid is ingested and regardless of whether the fluid contains carbohydrates or electrolytes, in both a thermoneutral and in a hot, humid environment. Accepted: 30 October 1997     

Assessment of a liposomal formulation of ivermectin in rabbit after a single subcutaneous administration

Ivermectin is a member of the macrocyclic lactone family widely used in livestock, pets, and humans as a potent parasiticide. Slight differences in formulation may change the plasma kinetics and efficacy of these compounds. The aim of the study is to evaluate the ability of a liposomal formulation of ivermectin to generate an efficient exposure of the animal to the drug. Ten rabbits were subcutaneously administered with 0.3 mg kg⁻¹ of ivermectin using Ivomec (n=5) or a liposomal formulation (n=5). The areas under serum concentration–time curve were similar after both treatments, indicating the same bioavailability for the two formulations. However, the liposomal formulation gave a higher C _max value (33.33 ng ml⁻¹) compared with Ivomec (20.82 ng ml⁻¹) and a significantly faster absorption as indicated by the T _max of 0.23 days compared with 1.13 days for the Ivomec formulation. The use of liposomal formulation shows promise as this system improves the efficacy of ivermectin and related drugs.     

Effects of improvement in aerobic power on resting insulin and glucose concentrations in children

In this study we determined the influence of improving aerobic power (V˙O_2max) on basal plasma levels of insulin and glucose of 11- to 14-year-old children, while accounting for body fat, gender, pubertal status, and leisure-time physical activity (LTPA) levels. Blood samples were obtained from 349 children after an overnight fast and analyzed for plasma insulin and glucose. Height, mass, body mass index (BMI), and sum of skinfolds (Σ triceps + subscapular sites) were measured. LTPA levels and pubertal status were estimated from questionnaires, and V˙O_2max was predicted from a cycle ergometry test. Regardless of gender, insulin levels were significantly correlated (P = 0.0001) to BMI, skinfolds, pubertal stage, and predicted V˙O_2max, but were not related to LTPA levels. Fasting glucose levels were not correlated to measures of adiposity or exercise (LTPA score, V˙O_2max) for females; however, BMI and skinfolds were correlated for males (P < 0.006). The children then took part in an 8-week aerobic exercise program. The 60 children whose V˙O_2max improved (≥3 ml · kg⁻¹ · min⁻¹) had a greater reduction in circulating insulin than the 204 children whose V˙O_2max did not increase −16 (41) vs −1 (63) pmol · l⁻¹; P = 0.028. The greatest change occurred in those children with the highest initial resting insulin levels. Plasma glucose levels were slightly reduced only in those children with the highest insulin levels whose V˙O_2max improved (P < 0.0506). The results of this study indicate that in children, adiposity has the most significant influence on fasting insulin levels; however, increasing V˙O_2max via exercise can lower insulin levels in those children with initially high levels of the hormone. In addition, LTPA does not appear to be associated with fasting insulin status, unless it is sufficient to increase V˙O_2max. Accepted: 2 June 1999     

High-intensity exercise decreases muscle buffer capacity via a decrease in protein buffering in human skeletal muscle

We have previously reported an acute decrease in muscle buffer capacity (βm_{in vitro}) following high-intensity exercise. The aim of this study was to identify which muscle buffers are affected by acute exercise and the effects of exercise type and a training intervention on these changes. Whole muscle and non-protein βm_{in vitro} were measured in male endurance athletes (VO_2max = 59.8 ± 5.8 mL kg⁻¹ min⁻¹), and before and after training in male, team-sport athletes (VO_2max = 55.6 ± 5.5 mL kg⁻¹ min⁻¹). Biopsies were obtained at rest and immediately after either time-to-fatigue at 120% VO_2max (endurance athletes) or repeated sprints (team-sport athletes). High-intensity exercise was associated with a significant decrease in βm_{in vitro} in endurance-trained males (146 ± 9 to 138 ± 7 mmol H⁺·kg d.w.⁻¹·pH⁻¹), and in male team-sport athletes both before (139 ± 9 to 131 ± 7 mmol H⁺·kg d.w.⁻¹·pH⁻¹) and after training (152 ± 11 to 142 ± 9 mmol H⁺·kg d.w.⁻¹·pH⁻¹). There were no acute changes in non-protein buffering capacity. There was a significant increase in βm_{in vitro} following training, but this did not alter the post-exercise decrease in βm_{in vitro}. In conclusion, high-intensity exercise decreased βm_{in vitro} independent of exercise type or an interval-training intervention; this was largely explained by a decrease in protein buffering. These findings have important implications when examining training-induced changes in βm_{in vitro}. Resting and post-exercise muscle samples cannot be used interchangeably to determine βm_{in vitro}, and researchers must ensure that post-training measurements of βm_{in vitro} are not influenced by an acute decrease caused by the final training bout.     

Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts

Inhibition of endothelin-A (ET_A) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study, we investigate the effect of ET_A-receptor inhibition on the development of regional alterations of the transient outward K⁺ current (I _to) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague–Dawley rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ET_A-receptor antagonist darusentan (LU135252, 35 mg [kg body weight]⁻¹ day⁻¹) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p < 0.001) and caused a significant reduction in I _to (at +40 mV) in epicardial myocytes (19.5 ± 1.2 pA pF⁻¹, n = 32 vs 23.2 ± 1.2 pA pF⁻¹, n = 35, p < 0.05). Darusentan further reduced I _to in AS (15.4 ± 1.3 pA pF⁻¹, n = 37, p < 0.05) and sham-operated animals (19.8 ± 1.6 pA pF⁻¹, n = 48, ns.). The effects of AS and darusentan on I _to were significant and independent as tested by two-way analysis of variance. I _to was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude of I _to in the epicardial region of the left ventricle but that ET_A-receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy.     

Prediction of <Emphasis Type="Italic">V</Emphasis>O<Subscript>2max</Subscript> with daily step counts for Japanese adult women

The purpose of the study was to develop a new non-exercise VO_2max prediction model using a physical activity (PA) variable determined by pedometer-determined step counts (SC, steps day⁻¹) in Japanese women aged 20–69 years old. Eighty-seven and 102 subjects were used to develop the prediction model, and to validate the new model, respectively. VO_2max was measured using a maximal incremental test on a bicycle ergometer. SC was significantly related to VO_2max (partial correlation coefficient r = 0.40, P < 0.001) after adjusting for BMI (kg m⁻²) and age (years). When the new prediction equation developed by multiple regression to estimate VO_2max from age, BMI, and SC (R = 0.71, SEE = 5.3 ml kg⁻¹ min⁻¹, P < 0.001) was applied to the Validation group, predicted VO_2max correlated well with measured VO_2max (r = 0.81, P < 0.001), suggesting that SC is a useful PA variable for non-exercise prediction of VO_2max in Japanese women.     

Influence of body mass on maximal oxygen uptake: effect of sample size

Basal metabolic rate is scaled to body mass to the power of 0.73, and we evaluated whether a similar scaling applies when the O₂ transport capacity of the body is challenged during maximal exercise (i.e. at maximal O₂ uptake, V˙O _2max). The allometric relationship between V˙O _2max and body mass (y=a · x ^b, where y is V˙O _2max and x is body mass) was developed for 967 athletes representing 25 different sports, with up to 157 participants in each sport. With an increasing number of observations, the exponent approached 0.73, while for ventilation the exponent was only 0.55. By using the 0.73 exponent for V˙O _2max, the highest value [mean (SD)] for the males was obtained for the runners and cyclists [234 (16) ml · kg^−0.73 · min⁻¹], and for the females the highest value was found for the runners [189 (14) ml · kg^−0.73 · min⁻¹]. For the females, aerobic power was about 80% of the value achieved by the males. Scaling may help both in understanding variation in aerobic power and in defining the physiological limitations of work capacity. Accepted: 3 November 2000     

Aldosterone-induced changes in the cardiac L-type Ca2+ current can be prevented by antioxidants in vitro and are absent in rats on low salt diet

Mineralocorticoid receptor (MR) activation modulates cardiac L-type Ca²⁺ current (I _CaL) and transient outward K⁺ current (I _to). The exact circumstances of MR activation, however, remain elusive. Here, we investigate the influence of corticosteroids on MR-mediated changes in cellular electrophysiology. In vitro incubation of adult rat ventricular myocytes with the MR agonist aldosterone (100 nM, 24 h) increased I _CaL density by 34% (n = 16; p < 0.01). This effect was abrogated by co-incubation with the MR antagonist spironolactone (10 μM). To investigate whether an increase in serum aldosterone concentration is sufficient for an increase in I _CaL in vivo, rats were subjected to low Na⁺ diet (LSD, 0.013% Na⁺) for 28 days. This increased serum aldosterone concentration from 0.19 ± 0.04 nM (n = 6) in control animals (0.3% Na⁺, CSD) to 16.1 ± 2.1 nM (n = 6; p < 0.0001). Strikingly, I _CaL density was similar in both CSD and LSD rats (−12.9 ± 0.9 pA pF⁻¹, n = 18 and −13.7 ± 1.1 pA pF⁻¹, n = 16, respectively), as was I _to density. In vitro, the glucocorticoid corticosterone (1 μM) also increased I _CaL and this effect was blocked by spironolactone (10 μM). Co-incubation with corticosterone (1 μM, the normal serum concentration) and aldosterone (100 nM, mimicking low Na⁺ intake) did not further increase I _CaL compared to corticosterone alone. Moreover, co-incubation of myocytes with N-acetylcysteine (10 mM) prevented the aldosterone (100 nM) or corticosterone (1 μM)-induced increase in I _CaL. In conclusion, an increase in serum aldosterone concentration in response to LSD is not sufficient for an increase in I _CaL density in cardiomyocytes in vivo. This is supported in vitro by the absence of an effect of aldosterone on I _CaL in the presence of a physiological concentration of corticosterone. Moreover, the cellular redox state may modulate MR activation. Michael Wagner and Elena Rudakova contributed equally to this work.     

Attenuated β-adrenoceptor-mediated cardiac contractile responses following androgenic steroid administration to sedentary rats

Androgenic steroids administered in doses at pharmacological levels to sedentary animals have been shown to result in a reduced β-adrenoceptor-mediated increase in systolic cardiac performance when assessed in vivo. Whether the attenuated adrenergic response occurs as a consequence of alterations in either cardiac loads, heart rate, modifications in left ventricular (LV) geometry, or a decrease in myocardial contractile performance has not been determined. In this study the effect of chronic administration (over 3 months) of an androgenic steroid (nandrolone decanoate, 5 mg · kg⁻¹ biweekly) on the response of load-insensitive indices of myocardial contractile function [the slope of the LV systolic stress-strain relationship (LV-Eⁿ _max, where Eⁿ _max is systolic myocardial elastance)] to an adrenergic-inotropic stimulus was examined ex vivo in paced rat hearts. Systolic cardiac performance was assessed at 300 beats · min⁻¹ in isolated constant flow perfused heart preparations both before and during 10^−8.5 mol · l⁻¹ isoproterenol (ISO) infusion (approximate concentration of ISO eliciting 50% maximal inotropic response to ISO). Steroid administration resulted in left-shifted LV systolic and diastolic pressure-volume (P-V ) relationships. The leftshifted P-V relationships were attributed, in part, to increased slopes of these relationships. However, the steroid-mediated increment in the slope of the systolic P-V relationship (systolic chamber elastance, E_max) was not associated with a similar change in LV Eⁿ _max [control 19.2 (SEM 2.1) g · cm⁻², steroid 18.3 (SEM 2.4) g . cm⁻²] as determined in the absence of ISO. Isoproterenol infusion resulted in an increase in both E_max and Eⁿ _max in the control rats, without altering systolic performance in the steroid treated rats. Consequently, in the presence of ISO, the steroid treated rats exhibited a similar E_max, but a reduction in Eⁿ _max compared to the control rats [control 25.6 (SEM 1.9) g · cm⁻², steroid 18.5 (SEM 1.5) g · cm⁻²; P < 0.05]. In conclusion, these results would suggest that chronic high dose androgenic steroid administration produces a decrease in myocardial contractile reserve to β-adrenoceptor stimulation. Accepted: 3 September 1999     

Seaweeds as a source of lead compounds for the development of new antiplasmodial drugs from South East coast of India

The problems of resistant lines of Plasmodium falciparum are escalating. Twelve seaweeds species belong to five different families (Sargassaceae, Gracilariaceae, Hypneaceae, Corallinaceae and Halimedaceae) were collected from Mandapam coastal area, and the seaweeds extracts were tested for in vitro antiplasmodial activity against P. falciparum. Among the tested seaweeds, Gracilaria verrucosa (IC₅₀ 5.55 μg.ml⁻¹) and Hypnea espera (IC₅₀ 8.94 μg.ml⁻¹) showed good antiplasmodial activity, and these results are comparable with positive controls such as artemether (IC₅₀ 4.09 μg.ml⁻¹) and chloroquine (IC₅₀ 19.59 μg.ml⁻¹), respectively. Turbinaria conoides, Sargassum myriocystem, Hypnea valentiae and Jania rubens extracts showed IC₅₀ values between 5 to 50 μg.ml⁻¹. Sargassum sp., Turbinaria decurrens and Halimeda gracilis extracts showed IC₅₀ values between 50 to 100 μg.ml⁻¹. Gracilaria corticata, Jania adherens and Halimeda opuntia extracts showed IC₅₀ value of more than 100 μg.ml⁻¹. Statistical analysis reveals that significant in vitro antiplasmodial activity (P < 0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out, and it shows that no morphological changes in erythrocytes by the ethanolic extract of seaweeds extracts after 48 h of incubation. The in vitro antiplasmodial activity might be due to the presence of sugars, proteins, phenols and carboxylic acid in the ethanolic extracts of seaweeds. It is concluded from the present study that the ethanolic extracts of seaweeds of G. verrucosa and Hypnea espera possess lead compounds for development of antiplasmodial drugs.     

Measurement and prediction of peak shivering intensity in humans

Prediction equations of shivering metabolism are critical to the development of models of thermoregulation during cold exposure. Although the intensity of maximal shivering has not yet been predicted, a peak shivering metabolic rate (Shiv_peak) of five times the resting metabolic rate has been reported. A group of 15 subjects (including 4 women) [mean age 24.7 (SD 6) years, mean body mass 72.1 (SD 12) kg, mean height 1.76 (SD 0.1) m, mean body fat 22.3 (SD 7)% and mean maximal oxygen uptake (V˙O_2max) 53.2 (SD 9) ml O₂ · kg⁻¹ · min⁻¹] participated in the present study to measure and predict Shiv_peak. The subjects were initially immersed in water at 8°C for up to 70 min. Water temperature was then gradually increased at 0.8 °C · min⁻¹ to a value of 20 °C, which it was expected would increase shivering heat production based on the knowledge that peripheral cold receptors fire maximally at approximately this temperature. This, in combination with the relatively low core temperature at the time this water temperature was reached, was hypothesized would stimulate Shiv_peak. Prior to warming the water from 8 to 20 °C, the oxygen consumption was 15.1 (SD 5.5) ml · kg⁻¹ · min⁻¹ at core temperatures of approximately 35 °C. After the water temperature had risen to 20 °C, the observed Shiv_peak was 22.1 (SD 4.2) ml O₂ · kg⁻¹ · min⁻¹ at core and mean skin temperatures of 35.2 (SD 0.9) and 22.1 (SD 2.2) °C, respectively. The Shiv_peak corresponded to 4.9 (SD 0.8) times the resting metabolism and 41.7 (SD 5.1)% of V˙O_2max. The best fit equation predicting Shiv_peak was Shiv_peak (ml O₂ · kg⁻¹ · min⁻¹)=30.5 + 0.348 ×V˙O_2max (ml O₂ · kg⁻¹ · min⁻¹) − 0.909 × body mass index (kg · m⁻²) − 0.233 × age (years); (P=0.0001; r ²=0.872). Accepted: 7 September 2000     

Physical activity and plasma interleukin-6 in humans – effect of intensity of exercise

The present study included data from three marathon races to investigate the hypothesis that a relationship exists between running intensity and elevated concentrations of interleukin (IL)-6 in plasma. The study included a total of 53 subjects whose mean age was 30.6 [95% confidence interval (CI) 1.4] years, mean body mass 77.7 (95%CI 2.0) kg, mean maximal oxygen uptake (V˙O_2max) 59.3 (95%CI 1.4) ml · min⁻¹ · kg⁻¹, and who had participated in the Copenhagen Marathons of 1996, 1997 or 1998, achieving a mean running time of 206 (95%CI 7) min. Running intensity was calculated as running speed divided by V˙O_2max. The concentration of IL-6 in plasma peaked immediately after the run. There was a negative correlation between peak IL-6 concentration and running time (r=−0.30, P < 0.05) and a positive correlation between peak IL-6 concentration and running intensity (r=0.32, P < 0.05). The IL-1 receptor antagonist (IL-1ra) plasma concentration peaked 1.5 h after the run and there was a positive correlation between the peak plasma concentrations of IL-6 and IL-1ra (r=0.39, P < 0.01). Creatine kinase (CK) plasma concentration peaked on the 1st day after the run, but no association was found between peak concentrations of IL-6 and CK. In conclusion, the results confirmed the hypothesized association between plasma IL-6 concentration and running intensity, but did not confirm the previous finding of a connection between IL-6 plasma concentration and muscle damage. Accepted: 6 August 2000     

In vitro antiplasmodial activity of ethanolic extracts of seaweed macroalgae against <Emphasis Type="Italic">Plasmodium falciparum</Emphasis>

Malaria is a major health problem in many developing countries. The drugs resistant Plasmodium falciparum causes the most virulent form of malaria in humans and it is described as a public health disaster causing increased morbidity and mortality. Thirteen seaweeds species which belong to four different families (Rhodomelaceae, Cladophoraceae, Ulvaceae, and Caulerpaceae) were collected from Mandapam coastal area and the seaweeds extracts were tested for in vitro antiplasmodial activity against P. falciparum. Among them, Caulerpa toxifolia (IC₅₀ 5.06 μg·ml⁻¹) showed potential antiplasmodial activity than other seaweeds extracts and it can be comparable with the positive control artemether (IC₅₀ 4.09 μg·ml⁻¹). Caulerpa peltata (IC₅₀ 16.69 μg·ml⁻¹) also exhibited good antiplasmodial activity and the IC₅₀ value is lesser than the positive control chloroquine (IC₅₀ 19.59 μg·ml⁻¹). Statistical analysis reveals that significant in vitro antiplasmodial activity (P < 0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out and it shows that no morphological changes in erythrocytes by the ethanolic extract of seaweeds extracts after 48 h of incubation. The in vitro antiplasmodial activity might be due to the presence of sugars, proteins, and phenols in the ethanolic extracts of seaweeds. It is concluded from the present study that, the ethanolic extracts of seaweeds of C. toxifolia and C. peltata possesses lead compounds for development of antiplasmodial drugs.     

In vitro antifilarial activity of glutathione S-transferase inhibitors

Female adult bovine filarial worms Setaria digitata were extracted with phosphate-buffered saline (pH 7.4) and glutathione S-transferase (GST) activity and protein content were determined. The protein content, GST enzyme activity, and specific activity were 10.61 ± 3.41 mg ml⁻¹, 0.09 ± 0.019 μmol min⁻¹ ml⁻¹, and 0.009 ± 0.002 μmol min⁻¹ mg⁻¹ protein, respectively. The GST inhibition studies were performed with and without the inhibitors resulted from earlier molecular docking studies viz., ethacrynic acid, plumbagin, and curcumin for which the IC₅₀ values were 19.42, 51.41, and 114.86 μM, respectively. The in vitro macrofilaricidal activity of these molecules was studied by worm motility and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay at 24- and 48-h incubation. Plumbagin and ethacrynic acid showed 100% inhibition in worm motility at lower concentrations of 3.19 and 6.6 μM, respectively, at 48-h incubation while curcumin was effective at 54.29 μM. In MTT reduction assay, the ED₅₀ values (50% inhibition in formazan formation) for plumbagin, ethacrynic acid, and curcumin at 48-h incubation were 1.20, 2.48, and 19.86 μM, respectively. MTT reduction assay showed that plumbagin was the most effective in killing the adult S. digitata worms followed by ethacrynic acid and curcumin. In conclusion, all the three molecules selected by molecular modeling and docking studies inhibited the GST enzyme isolated from S. digitata and exhibited macrofilaricidal activity in vitro.     

Diurnal variation in the salivary melatonin responses to exercise: relation to exercise-mediated tachycardia

Salivary melatonin concentration is an established marker of human circadian rhythmicity. It is thought that melatonin is relatively robust to the masking effects of exercise. Nevertheless, the extent and even the direction of exercise-related change is unclear, possibly due to between-study differences in the time of day exercise is completed. Therefore, we aimed to compare melatonin responses between morning and afternoon exercise, and explore the relationships between exercise-related changes in melatonin and heart rate. At 08:00 and 17:00 hours, seven male subjects (mean ± SD age, 27 ± 5 years) completed 30 min of cycling at 70% peak oxygen uptake followed by 30 min of rest. Light intensity was maintained at ~150 lx. Salivary melatonin (ELISA) and heart rate were measured at baseline, 15 min during exercise, immediately post-exercise and following 30 min recovery. Melatonin was ≈15 pg ml⁻¹ higher in the morning trials compared with the afternoon (P = 0.030). The exercise-related increase in melatonin was more pronounced (P = 0.024) in the morning (11.1 ± 8.7 pg ml⁻¹) than in the afternoon (5.1 ± 5.7 pg ml⁻¹). The slope of the heart rate–melatonin relationship was significantly (P = 0.020) steeper in the morning (0.12 pg ml⁻¹ beats⁻¹ min⁻¹) than in the afternoon (0.03 pg ml⁻¹ beats⁻¹ min⁻¹). In conclusion, we report for the first time that the masking effect of moderate-intensity exercise on melatonin is approximately twice as high in the morning than the afternoon. The much steeper relationship between heart rate and melatonin changes in the morning raises the possibility that time of day alters the relationships between exercise-mediated sympathetic nervous activity and melatonin secretion.     

Effect of exercise on the mitochondrial DNA content of peripheral blood in healthy women

Exercise decreases insulin resistance and increases maximal exercise capacity as estimated from maximal oxygen uptake (V˙O_2max). Recent reports have demonstrated that the mitochondrial DNA (mtDNA) content of blood is correlated with V˙O_2max in healthy subjects (mean age 31 years) and is inversely correlated with insulin resistance parameters. The aim of this study was to determine the effect of regular exercise on the mtDNA content in the peripheral blood of 16 healthy young women of mean age 24.8 (SD 6.2) years and 14 healthy older women of mean age 66.7 (SD 5.8) years. The exercise programme lasted for 10 weeks and consisted of three sessions a week, each of 1 h and aiming to attain 60%–80% of V˙O_2max. The mtDNA content of peripheral blood was measured by competitive polymerase chain reaction. The V˙O_2max had significantly increased following the exercise programme [from 33.1 (SD 3.4) to 35.2 (SD 3.4) ml · kg⁻¹ · min⁻¹ in the young and from 24.3 (SD 5.3) to 30.3 (SD 7.3) ml · kg⁻¹ · min⁻¹ in the older women, both P < 0.05]. Exercise decreased systolic blood pressure, and concentrations of triglyceride, low density lipoprotein-cholesterol (LDL-C), glucose and insulin in the blood of the young and of total cholesterol, LDL-C and glucose in that of the older women. High density lipoprotein-cholesterol (HDL-C) in the young women was increased by exercise. The mtDNA content significantly increased following the exercise programme in both groups [from 27.1 (SD 17.9) to 52.7 (SD 44.6) amol · 5 ng⁻¹ genomic DNA in the young and from 15.3 (SD 10.2) to 32.1 (SD 30.0) amol · 5 ng⁻¹ genomic DNA in the older women, both P < 0.05]. There was a significant positive correlation between the change in mtDNA content and the change in V˙O_2max (r=0.74 in the young and r=0.71 in the older women, both P < 0.01). In conclusion, 10 weeks of moderate intensity, regular exercise increased the mtDNA content in peripheral blood and decreased insulin resistance parameters. This data suggests that increase in the mtDNA content may be associated with increased insulin sensitivity. Accepted: 15 April 2000     

Physiological and metabolic responses of female games and endurance athletes to prolonged, intermittent, high-intensity running at 30° and 16°C ambient temperatures

Eight female games players (GP) and eight female endurance athletes (EA) ran intermittently at high-intensity and for prolonged periods in hot (30°C) and moderate (16°C) ambient temperatures. The subjects performed a two-part (A, B) test based on repeated 20-m shuttle runs. Part A comprised 60 m of walking, a maximal 15-m sprint, 60 m of cruising (90% maximal oxygen uptake, V˙O_2max) and 60 m of jogging (45% V˙O_2max) repeated for 75 min with a 3-min rest every 15 min. Part B involved an exercise and rest pattern of 60-s running at 100% V˙O_2max and 60-s rest which was continued until fatigue. Although the GP and EA did not respond differently in terms of distances completed, performance was 25 (SEM 4)% less (main effect trial, P < 0.01) in the hot (HT) compared with the moderate trial (MT). Sprints of 15 m took longer to complete in the heat (main effect, trial, P < 0.01), and sprint performance declined during HT but not MT (interaction, trial × time, P < 0.01). A very high correlation was found between the rate of rise in rectal temperature in HT and the distance completed [GP, r =−0.94, P < 0.01; EA (n = 7), r = −0.93, P < 0.01]. Blood lactate [La⁻ ]_b and plasma ammonia [NH₃]_p1 concentrations were higher for GP than EA, but were similar in HT and MT [La⁻ ]_b, HT: GP vs EA, 8.0 (SEM 0.9) vs 4.9 (SEM 1.1) mmol · l⁻¹; MT: GP vs EA, 8.0 (SEM 1.3) vs 4.4 (SEM 1.2) mmol · l⁻¹; interaction, group × time, P < 0.01; [NH₃]_p1, HT: GP vs EA, 70.1 (SEM 12.7) vs 43.2 (SEM 6.1) mmol · l⁻¹; MT: GP vs EA, 76.8 (SEM 8.8) vs 32.5 (SEM 3.8) μmol · l⁻¹; interaction, group × time, P < 0.01. Ad libitum water consumption was higher in HT [HT: GP vs EA, 18.9 (SEM 2.9) vs 13.5 (SEM 1.7) ml · kg⁻¹ · h⁻¹; MT: GP vs EA, 12.7 (SEM 3.7) vs 8.5 (SEM 1.5) ml · kg⁻¹ · h⁻¹; main effect, group, n.s.; main effect, trial, P < 0.01]. These results would suggest that elevated body temperature is probably the key factor limiting performance of prolonged, intermittent, high-intensity running when the ambient temperature is high, but not because of its effect on the metabolic responses to exercise. Accepted: 19 July 1999