Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy.

In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.

Graded vascular autonomic control versus discontinuous cardiac control during gradual upright tilt.

Indexes of heart rate variability (HRV) and the slope of cardiac baroreflex are extensively used for non invasive assessment of circulatory autonomic control in pathophysiology. We performed this study (1) to assess the sensitivity of these indexes towards small graded postural stimulations and (2) to delineate the informations provided about the settings of both vascular tone and cardiac activity. Twenty healthy subjects were randomly tilted for eight minutes at each of the six angles: -10 degrees, 0 degrees (supine), 10 degrees, 30 degrees, 45 degrees, and 60 degrees. Instant RR-interval and finger blood pressure (BP) were continuously recorded, and venous blood was collected at the end of each 8 min position for catecholamines determination. Group average heart rate, noradrenaline and diastolic BP (DBP) increased linearly with head-up tilt angle from 10 degrees. Systolic BP (SBB) ranked only two distinct series -10 degrees, 0 degrees, 10 degrees versus 30 degrees, 45 degrees, 60 degrees, as did the number of spontaneous baroreflex (SBR) sequences. The spectral power of the low-frequency (LF) and high-frequency (HF) of RR variability and the ratio LF/HF changed rather abruptly from either 30 degrees or 45 degrees, depending on each individual. Both HF/tot i.e. the ratio of HF to total spectral RR variability and the slope of SBR decreased markedly from 10 degrees to 30 degrees and less but more gradually from 30 degrees to 60 degrees. Thus, our observations argue for gradual adjustments of vascular tone as reflected by highly consistent changes in plasma noradrenaline and diastolic arterial pressure, contrasting with a main discontinuous autonomic setting of cardiac activity as reflected by changes in the harmonic components of spectral RR variability and in the slope of cardiac baroreflex. The pattern of changes in systolic arterial pressure attested the discontinuous cardiac autonomic control rather than the gradual setting of arterial tone. We submit that these different patterns of autonomic adjustments should be considered when assessing pathophysiological states.

Abnormal autonomic cardiovascular control in ankylosing spondylitis.

OBJECTIVE: This study was aimed at assessing the contribution of the autonomic nervous system to adjustments of cardiovascular function in patients with ankylosing spondylitis (AS). METHODS: In 18 AS patients (mean age: 34.9; mean disease duration: 6.4 years) and 13 healthy controls (mean age: 31.7) the changes of heart rate (HR) with deep breathing (E/I ratio) and standing up (30/15 ratio) were recorded. The slope of cardiac baroreflex, the times series of blood pressure and HR values upon lying and standing, and venous plasma concentrations of catecholamines were also analysed. Erythrocyte sedimentation rate (ESR), plasma C reactive protein (CRP) concentration and a clinical index (BASDAI score) were used to assess the degree of disease activity in patients. RESULTS: In the standing patients, blood pressure was found to decrease progressively (p< 0.001). Furthermore, the patients with a BASDAI score > 5 had a higher heart rate than patients with a BASDAI score < 5 (p<0.02), and there was a trend for a similar difference when patients were classified according to their ESR and CRP. Plasma catecholamine concentrations and the E/I ratio were not different in patients from controls. The 30/15 ratio and the slope of the spontaneous baroreflex during standing were both lower in AS patients than controls (p< 0.01). CONCLUSIONS: This study demonstrated a change in autonomic nervous system function of AS patients, with a decreased parasympathetic activity, as evidenced by higher HR and lower baroreflex slope. As these significant deviances were mainly observed in patients with more active (or more inflammatory) disease, the autonomic nervous system involvement could be related to the inflammatory process. This autonomic strain may be related to the cardiac involvement in AS patients.

Active standing and passive tilting similarly reduce the slope of spontaneous baroreflex in healthy subjects.

Non-invasive assessment of the sensitivity of cardiac baroreflex was performed by recording each RR-interval and each blood pressure cycle (Finapres). In sequences of at least three cardiac cycles in which systolic blood pressure and RR-interval had changed in the same direction, the slope of linear regression of RR duration as a function of the change in systolic arterial pressure was taken for estimating the sensitivity of the spontaneous cardiac baroreflex. This technique was used in healthy humans to examine how a postural change from supine to upright by either active standing up or 60 degrees head-up tilting modified the sensitivity of the spontaneous baroreflex. We observed that the slope of the spontaneous baroreflex averaged 14.6 +/- 2 ms.mm Hg-1 during rest in the supine position, and decreased to 7.8 +/- 1.2 ms.mm Hg-1 (p < 0.05) after active standing, while the number of sequences was significantly increased in the upright as compared to the supine position. Head-up tilting by 60 degrees led to values similar to those following active standing. The adjustment of baroreflex slope to either postural change occurred in a few seconds, so that posture-characteristic values were obtained from five-minute records. We conclude that non-invasive recording of spontaneous sequences of related changes in blood pressure and RR-interval during several minutes provides reproducible values of the slope of cardiac baroreflex in the supine and upright position. This easy and reliable determination of the sensitivity of the cardiac baroreflex might prove to be useful when assessment of baroreflex function is needed.

Effects of i.v. insulin bolus on urinary calcium and oxalate excretion in healthy subjects.

Oral glucose load increases urinary excretion of calcium (Ca) and oxalate. Although this increase in calciuria is commonly ascribed to insulin, the role of glucose on Ca excretion remains unclear. In order to assess the role of glucose changes on calciuric response to insulin and oxalate excretion, hypoglycemia induced by insulin (hypo) and hyperglycemia induced by oral glucose load (hyper) were studied in 7 healthy subjects on two separate days. As expected, glycemia dropped in hypo (-70%, p<0.001) and increased in hyper (+67%, p<0.001). Calciuria increased on the two days,+205%, p<0.001 (hypo) vs + 43%, p < 0.05 (hyper) as a result of both a rise in calcium filtered load (FCa) and a decrease in tubular reabsorption of calcium (TRCa). While the increase in FCa was similar in the two situations, the higher increased calciuria in hypo (p<0.01) was linked to a deeper decrease in TRCa, - 2.1 % (hypo) vs - 1.4% (hyper), p < 0.01. Although the estimated amounts of insulin were similar in the two situations, the insulin kinetics were different. Thus, after insulin injection, the putative role of the high initial insulin spike in triggering the increase in calciuria cannot be ruled out. The deeper decrease in TRCa (hypo) was also likely due to both hypoglycemia and changes in counter-regulation hormones. In conclusion, calciuria increased after either hypo or hyperglycemia and the higher increase in calciuria observed in hypo was subsequent to a deeper decrease in tubular Ca reabsorption. Oxaluria did not change in hypo, while it increased in hyper.

Aspartame ingestion increases urinary calcium, but not oxalate excretion, in healthy subjects.

Aspartame is the artificial sweetener most extensively used as a substitute for glucose or sucrose in the food industry, particularly in soft drinks. As glucose ingestion increases calciuria and oxaluria, the two main determinants of urinary calcium-oxalate saturation, we considered it worthwhile to determine whether aspartame ingestion also affects calcium-oxalate metabolism. Our study compares the effects of the ingestion of similarly sweet doses of aspartame (250 mg) and glucose (75 g) on calcium and oxalate metabolisms of seven healthy subjects. Urinary calcium excretion increased after the intake of both aspartame (+86%; P < 0.01) and glucose (+124%; P < 0.01). This may be due to the rise in calcemia observed after both aspartame (+2.2%; P < 0.05) and glucose ingestion (+1.8%; P < 0.05). The increased calcemia may be linked to the decrease in phosphatemia that occurred after both aspartame (P < 0.01) and glucose (P < 0.01) load. Aspartame did not alter glycemia or insulinemia, whereas glucose intake caused striking increases in both glycemia (+59%; P < 0.001) and insulinemia (+869%; P < 0.01). Although insulin was considered the main calciuria-induced factor after glucose load, it is unlikely that this mechanism played a role with aspartame. Urinary oxalate excretion did not change after aspartame, whereas it increased (+27%; P < 0.05) after glucose load. Thus, as aspartame induced a similar increase in calciuria as did glucose but, conversely, no change in oxaluria, substituting glucose by aspartame in soft drinks may appear to be of some potential benefit.

Lack of increased urinary calcium-oxalate supersaturation in long-term kidney transplant recipients.

Nephrolithiasis is uncommon after kidney transplantation. However, calcium (Ca) supplementation, which has been proposed as a treatment of post-transplant osteopenia, might increase calciuria and bolster Ca stone formation. Therefore, in 24-hour urine of 82 normocalcemic long-term renal transplant recipients (RT) and in 82 healthy subjects (HS), we assessed some Ca nephrolithiasis risk factors and the Ca-salt saturation estimated by the ion-activity product index (AP) and relative supersaturation (RS). In RT, calciuria was lower (mean +/- SD, 3.20 +/- 2.25 vs. 4.61 +/- 1.71 mmol/day; P < 0.001), urinary volume higher (2.41 +/- 0.83 vs. 1.39 +/- 0.53 liter/day; P < 0.001), oxaluria higher (419 +/- 191 vs. 311 +/- 79 mumol/day; P < 0.001) and citraturia lower (1.40 +/- 1.36 vs. 3.77 +/- 1.36 mmol/day; P < 0.001) than in HS. As a result, Ca-oxalate supersaturation was lower in RT than HS (AP, 1.07 +/- 0.69 vs. 2.07 +/- 1.13, P < 0.001; and RS, 0.62 +/- 0.26 vs. 0.94 +/- 0.21, P < 0.001), and was similar in subgroups of RT (N = 37) and HS (N = 37) matched for urinary volume, demonstrating that even without any larger urinary volume, Ca-oxalate saturation was not higher in RT than HS, and suggesting that opposite changes in Ca and oxalate in RT likely canceled their effects on lithogenic risk. In RT which had similar urinary pH and phosphate (P) than HS, Ca-P supersaturation was lower than in HS for brushite (AP, 3.25 +/- 6.67 vs. 6.01 +/- 4.85, P < 0.001; RS, -0.33 +/- 0.76 vs. 0.48 +/- 0.53, P < 0.001) and octacalcium phosphate (RS, -0.95 +/- 0.72 vs. 0.21 +/- 0.85, P < 0.001), and similar for apatite. Finally, fasting calciuria and calciuric response to a single oral Ca load were similar in RT (N = 19) and HS (N = 8). Together, these results argue strongly against a higher risk of Ca stone formation in RT than HS, even in case of Ca supplementation.

Lack of evidence that cyclosporine treatment impairs calcium-phosphorus homeostasis and bone remodeling in normocalcemic long-term renal transplant recipients.

Since the effects of cyclosporine on mineral and bone metabolism are controversial, we studied calcium regulating hormones, calcium-phosphorus (Ca-P) metabolism, and bone remodeling, assessed by serum osteocalcin, in long-term renal transplant recipients (RT). Forty-seven normocalcemic patients with good renal function receiving cyclosporine (CT, n = 27) or not (NC, n = 20) were studied at baseline and after an oral Ca load. CT and NC had similar age, daily dose of steroids, GFR level, and duration of transplantation. Baseline evaluation included 24-hr urinary Ca, P, TRP, TmP/GFR, fasting serum intact PTH, 1,25-(OH)2D, 25OHD, osteocalcin, Ca, and P. Subjects of the two groups had excessive secretion of PTH, tubular P wasting, and high serum osteocalcin level, as is usual in RT. However, there was no difference between CT and NC regarding any baseline variable. Ten CT and ten NC, matched for duration of transplantation and serum PTH level, ingested 1g Ca to achieve an acute dynamic study of PTH secretion and Ca-P metabolism. In both CT and NC, this Ca load caused the same decreases in serum PTH (P < 0.001), NcAMP (P < 0.05), and urinary P (P < 0.001) and the same increases in serum and urinary Ca (P < 0.001), and in both TmP/GFR and TRP (P < 0.001). These results strongly suggest that cyclosporine treatment had no significant effect on calcium-regulating hormone secretion, P-Ca metabolism, and bone remodeling level. We therefore consider that cyclosporine is unlikely to have any prominent role in the abnormalities of bone endocrine and mineral metabolism that are common in long-term kidney recipients.

Increase in urinary calcium and oxalate after fructose infusion.

We have previously shown that an oral glucose load increased both calciuria and oxaluria while the ingestion of fructose induced a rise in calciuria and a decrease in oxaluria. This latter effect remains unclear and might be linked to the reduced intestinal oxalate absorption subsequent to digestive intolerance in some subjects. Such a hypothesis could be enlightened by the study of a parenteral fructose load. Therefore in 7 healthy subjects, we compared the effects of fructose infusion (F) (15 min iv infusion at 0.185 mmol/kg BW/min) to a control glucose infusion (G) on urinary calcium and oxalate. In this study, glycemia and insulinemia increased less after (F) than after (G) (respectively + 21% vs + 216%, p < 0.001 and + 230% vs + 402%, p < 0.05) and phosphatemia decreased less after (F) than after (G) (-7% vs -14%, p < 0.05). Urinary calcium and oxalate increased only after (F) (respectively + 64%, p < 0.01 and + 60%, p < 0.05). Urinary uric acid, another urolithiasis factor, increased after both (F) and (G) (respectively + 45%; p < 0.01 and + 42%; p < 0.01) but uricemia increased only after (F) (+ 25%; p < 0.01). Our results suggest an additional reason to avoid the use of fructose in parenteral nutrition, particularly in individuals with a known history of either calcium oxalate or urate urolithiasis.

Acute oral calcium load decreases parathyroid secretion and suppresses tubular phosphate loss in long-term renal transplant recipients.

Persistent hyperparathyroidism and impaired tubular reabsorption of phosphate (P) are common after kidney transplantation. In order to assess the suppressibility of these abnormalities, we studied the effects of a single oral calcium (Ca) load (1 g) in 7 healthy subjects (HS) and in 14 normocalcemic long-term renal transplant recipients with good renal function (RT). In HS and RT, serum and urinary Ca were similar at baseline, and increased (p < 0.001) to the same extent after Ca ingestion. Serum parathyroid hormone (PTH) and nephrogenic cAMP (NcAMP) levels were higher at baseline in RT than HS (mean +/- SEM; respectively, PTH 7.8 +/- 0.8 vs. 3.5 +/- 0.6 pmol/l, p < 0.001, and NcAMP 24.8 +/- 2.3 vs. 13.9 +/- 2.3 nmol/l GFR, p < 0.01). After Ca, PTH (p < 0.001) and NcAMP (p < 0.01) decreased markedly in both RT and HS. Maximal changes in PTH and NcAMP were larger in RT than HS (PTH - 3.3 +/- 0.4 vs. -2.1 +/- 0.03 pmol/l, p < 0.01, and NcAMP -18.2 +/- 3.3 vs. -8.1 +/- 2.6 nmol/l GFR, p < 0.05). Although PTH levels remained significantly higher in RT than HS from baseline to the end of the study (p < 0.001), PTH decreased to the normal range in RT after Ca load. Moreover, NcAMP reached similar values in RT and HS after Ca (16.0 +/- 3.3 vs. 13.2 +/- 2.8 nmol/l GFR at the end of the survey, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in calciuria and oxaluria after a single chocolate bar load.

Chocolate, a foodstuff rich in sucrose, fat and oxalate, is considered unsuitable in cases of obesity, diabetes mellitus, urolithiasis and postprandial hypoglycemia. However the pathophysiological effects of chocolate are poorly documented. Therefore we investigated the effects of ingestion of 100 g dark chocolate bar (45 g cocoa and 55 g sucrose) on carbohydrate, calcium and oxalate metabolisms in 10 healthy subjects. Results were compared to those of 55 g sucrose intake (control group) performed on another day. Chocolate caused i) a lesser but longer increase in plasma glucose, insulin, and C-peptide than sucrose (respectively +23% of baseline vs +60%, p < 0.001; +436% of baseline vs +755%, p < 0.01 and +200% of baseline vs +331%, p < 0.01), ii) a striking increase in triglyceridemia, calciuria and oxaluria (respectively +96%, p < 0.01; +147%, p < 0.01 and +213%, p < 0.001). Thus, chocolate (cocoa+sucrose) causes a lesser pancreatic stimulation than sucrose. However, the increases in both calciuria and oxaluria (induced respectively by sucrose and cocoa) following chocolate ingestion might contribute to urinary conditions favoring the development of calcium oxalate calculi.

Carbohydrate metabolism and urinary excretion of calcium and oxalate after ingestion of polyol sweeteners.

Polyols are widely used instead of glucose and sucrose in sweets and dietary products because they are barely cariogenic, and their energy value is lower. In addition, it has been shown that calciuria and oxaluria increase after an oral glucose (Glu) load. We, therefore, investigated the effects of a single polyol ingestion on carbohydrate, calcium, phosphate, and oxalate metabolism in 10 healthy subjects. On 5 experimental days, subjects ingested 20 g Glu, Lycasin (Lyc), Maltisorb (Mal), sorbitol (Sor), or xylitol (Xyl). Glu, Lyc, and Mal intake caused an increase in glycemia [respectively, +34% (P < 0.001), +15% (P < 0.001), and +15% (P < 0.001)], insulinemia [respectively, +358% (P < 0.001), +88% (P < 0.05), and +94% (P < 0.01)], and C-peptide level [respectively, +170% (P < 0.001), +15% (P < 0.01), and +15% (P < 0.001)]. Conversely, no change occurred in glycemia, insulinemia, or C-peptide levels after ingestion of Sor or Xyl. Urinary calcium increased after Glu (+64%; P < 0.01) and Xyl (+74%; P < 0.01) intake, and urinary phosphate increased after Xyl (+27%; P < 0.05), but decreased after a Glu load (-68%; P < 0.01). Only Xyl increased urinary excretion of oxalate (+53%; P < 0.05). Our results suggest that ingestion of polyols causes a much lesser pancreatic stimulation than Glu intake. Also, Lyc, Mal, and Sor sweeteners have no effect on urinary excretion of calcium and oxalate, whereas calciuria and oxaluria increase after Xyl ingestion.

Met-enkephalin, beta-endorphin and cortisol responses to sub-maximal exercise after sleep disturbances.

The present study compared the effects of partial sleep deprivation and the effects of an intake of a hypnotic compound (zolpidem) prior to bedtime, on sleep and on hormonal and metabolic adaptations to subsequent exercise. Sleep deprivation consisted of a delayed bedtime and an early getting-up time. Eight young subjects, who slept well and were highly trained athletes, were enrolled in this study. Sleep was recorded polygraphically and the following afternoon exercise was performed on a cycle ergometer for 30 min at 75% of maximal oxygen consumption (VO2max) after a 10-min warm up. Met-enkephalin, beta-endorphin, cortisol, and lactate concentrations were measured at rest and during exercise. The data obtained after experimental sleep, with and without medication were compared with those obtained in the reference condition with normal sleep. Both types of sleep reduction decreased the total sleep time, stage 2 sleep, and rapid eye movement sleep, whereas zolpidem administration did not modify either the duration of sleep or the sleep stages. After the reference night, plasma met-enkephalin did not show any significant change at the end of the submaximal exercise, whereas beta-endorphin, cortisol, and lactic acid concentrations increased significantly in all subjects. The changes in concentration in beta-endorphin were significantly related to the changes in cortisol (r = 0.78; P less than 0.01) and to the changes in plasma lactic acid (r = 0.58; P less than 0.05). Cortisol concentrations were also related to lactic acid values (r = 0.94; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma levels of beta-endorphin, prolactin and gonadotropins in male athletes after an international nordic ski race.

Plasma beta-endorphin, prolactin (PRL), FSH and LH were measured in 17 volunteer male subjects at rest and under the stress caused by a long-distance nordic ski race. The race induced increased levels of beta-endorphin and PRL in all skiers. The changes in PRL with exercise were significantly related to the changes in beta-endorphin (r = 0.69, p less than 0.001). Furthermore, the highly trained skiers training over 150 km.week-1 of nordic ski showed consistently higher post-exercise beta-endorphin and PRL levels than the moderately trained skiers who trained for 20 km.week-1. In addition the race induced slight falls in FSH and LH; however plasma gonadotropin levels did not show any correlation with plasma beta-endorphin concentrations and did not differ between the two groups of skiers. These results suggest that endogenous opioid peptides may modulate PRL secretion in heavy exercise, since they are of minor importance in the release of FSH and LH in such a situation. The observations also suggest that the degree of previous training and the exercise intensity do seem to be responsible for the hormonal changes.

[Comparative study of heparin and a very low molecular-weight heparin in hemodialysis in chronic renal insufficiency]. / Etude comparative de l'héparine et d'une héparine de très faible masse moléculaire en hémodialyse dans l'insuffisance rénale chronique.

In the course of dialysis sessions, we have compared the antithrombotic effect of two heparinization regimens: low molecular weight heparin (CY 222, mean molecular weight: 2,500, Institute Choay, France): 90 anti-Xa units/kg bodyweight as a bolus injection followed by a continuous infusion of 1,000 anti-Xa units/hour (regimen 1); or 300 anti-Xa units/kg as a bolus injection (regimen 3), with a standard heparinization regimen (100 IU/kg regimen 2). Eight patients received the 3 regimens successively. Factor IIa and factor Xa inactivation was measured by a method that uses chromogenic substrates. The frequency of adverse effects, ultrafiltration rates, creatinine and BUN clearances of the 3 regimens were similar, whereas dialyser blood loss was higher in the first regimen. At the dose of 300 anti-Xa units of CY 222 (regimen 3), inactivation of factor Xa was similar to Xa inhibition reached through the conventional treatment (regimen 2) but IIa inhibition was less pronounced.

[Radioimmunological assay of plasma arginine-vasopressin in man. Comparison of 2 methods of extraction]. / Dosage radioimmunologique de l'arginine-vasopressine plasmatique chez l'homme. Comparaison de deux méthodes d'extraction.

Two methods of extraction, prior to radio-immunoassay (RIA) of human plasma arginine vasopressin (AVP) were tested: ethanol extraction (ETH), chromatography with ODS-Silica (ODS-Sil). Recovery of 125I AVP was higher when using ODS-Sil than when using ETH. Recovery of standard AVP and plasma enriched with standard AVP was found to be more efficient and reproducible for ODS-Sil. However, the RIA used, performed after chromatography with ODS-Sil, is not enough sensitive to detect low concentrations but is able to detect high concentrations and physiological variations of plasma AVP.

Assessment of plasma opioid peptides, beta-endorphin and met-enkephalin, at the end of an international nordic ski race.

Plasma met-enkephalin, beta-endorphin, cortisol and lactic acid concentrations were measured in seventeen volunteer male subjects at rest and after a long-distance nordic ski race. Immediately after the race, mean plasma met-enkephalin did not show any significant change, but significant rises in beta-endorphin, cortisol and lactic acid were noted in all skiers. The change in beta-endorphin with exercise was significantly related to the change in cortisol (r = 0.68; p less than 0.001) and to the change in plasma lactic acid (r = 0.60; p less than 0.001). Furthermore, the experienced skiers training over 150 km X week-1 of nordic ski had significantly faster skiing times in this event and showed greater beta-endorphin, cortisol and lactic acid levels than the recreational skiers who trained for 20 km X week-1. Our results imply that the changes in plasma beta-endorphin depend on the intensity of exercise. However the significance of higher levels of skiing training or previous nordic ski experience in the release of beta-endorphin is expected and cannot be excluded.