A method for monitoring toxic damage to the liver,based on measurement of total water and its magnetic relaxation characteristics

Acute poisoning of rats with the hepatotropic poison tetrachloromethane was accompanied by increases in the liver content of total water and its spin-lattice (T ₁) and spin-spin (T ₂) relaxation times and by a decrease in theT ₁/T ₂ ratio, with reversal of the correlation betweenT ₁ andT ₂. The antihypoxic agent sodium γ-oxybutyrate normalized water metabolism in the liver almost completely. It is concluded that total water content andT ₁ are the more informative parameters for monitoring both toxic liver damage and the efficacy of its pharmacological correction. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 584–586, December, 1995 Presented by Yu. A. Vladimirov, Member of the Russian Academy of Medical Sciences     

Biological availability of endogenous calcitonin in rats

Significant correlation was established in 52-week-old rats between serum calcitonin content and density of sublemmal granules at the vascular pole of C-cells (N _Vsg)∶r _xy=0.922,p<0.001. Statistical simulation methods made it possible to determine the confidence interval of biological availability of endogenous calcitonin: 87–100% (p≥0.95). Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 4, pp. 474–476, April, 1998     

Hyperpnoea and CO2 sensitivity of the respiratory centres during exercise

Summary The aim of this study was to specify whether exercise hyperpnoea was related to the CO₂ sensitivity of the respiratory centres measured during steady-state exercise of mild intensity. Thus, ventilation , breathing pattern [tidal volume (V _T), respiratory frequency (f), inspiratory time (T _I), total time of the respiratory cycle (T _TOT),V _T/T _I,T _I/T _TOT] and CO₂ sensitivity of the respiratory centres determined by the rebreathing method were measured at rest (SCO_{2 re}) and during steady-state exercise (SCO_{2 ex}) of mild intensity [CO₂ output =20 ml·kg⁻¹·min⁻¹] in 11 sedentary male subjects (aged 20–34 years). The results showed that SCO_{2 re} and SCO_{2 ex} were not significantly different. During exercise, there was no correlation between and SCO_{2 ex} and, for the same , all subjects had very close values normalized for body mass (bm), regardless of their SCO_{2 ex} ( =1.44 l·min⁻¹·kg⁻¹ SD 0.10). A highly significant positive correlation between SCO_{2 ex} andV _T (normalised for bm) (r=0.80,P<0.01),T _I (r=0.77,P<0.01) andT _TOT (r=0.77,P<0.01) existed, as well as a highly significant negative correlation between SCO_{2 ex} and (normalised for bm^−0.25) (r=−0.73,P<0.01). We conclude that the hyperpnoea during steady-state exercise of mild intensity is not related to the SCO_{2 ex}. The relationship between breathing pattern and SCO_{2 ex} suggests that the breathing pattern could influence the determination of the SCO_{2 ex}. This finding needs further investigation.     

Accuracy of neuro-fuzzy logic and regression calculations in determining maximal lactate steady-state power output from incremental tests in humans

The aim of this study was to employ neuro-fuzzy logic and regression calculations to determine the accuracy of prediction of the power output (P) of the maximal lactate steady-state (MLSS) on a cycle ergometer calculated from the results of incremental tests. A group of 17 male and 17 female sports students underwent two incremental tests (a 1 min test T₁: initial exercise intensity 0.2 W·kg^–1 increasing 0.2 W·kg^–1 every minute; a 3 min test T₃: initial exercise intensity 0.6 W·kg^–1 increasing 0.6 W·kg^–1 every 3 min) and at least four constant-intensity tests of 30 min duration. Two models for MLSS calculation were developed using the data from T₁ and T₃, a forward stepwise linear regression model (REG) and a neuro-fuzzy model (FUZ). A group of 26 randomly selected subjects (model group, MG) were used to generate the REG and the FUZ models. The data from the remaining 8 subjects (4 men and 4 women; verifying group, VG) were used to verify the REG and FUZ models. The precision of the MLSS calculation in MG produced a better correlation when using data from T₁ (REG r=0.95, FUZ r=0.99) than data from T₃ (REG r=0.88, FUZ r=0.98). Our calculation models were confirmed using data from VG for T₁ (REG r=0.97, FUZ r=0.98) as well as for T₃ (REG r=0.97, FUZ r=0.97). Based on our subject population of young, healthy sport students, our results suggest that a single incremental test may be used for prediction of P at the MLSS using a cycle ergometer. Furthermore, the results from T₁ yielded higher correlations compared to T₃. Calculations from REG were similar to FUZ but the precision of REG and FUZ was better compared to calculations derived using data from a single threshold. Electronic Publication     

Relevance of individual characteristics for thermoregulation during exercise in a hot-dry environment

The aim of this study was to investigate the relevance of individual characteristics for thermoregulation during prolonged cycling in the heat. For this purpose, 28 subjects cycled for 60 min at 60% VO_2peak in a hot-dry environment (36 ± 1°C; 25 ± 2% relative humidity, airflow 2.5 m/s). Subjects had a wide range of body mass (99–43 kg), body surface area (2.2–1.4 m²), body fatness (28–5%) and aerobic fitness level (VO_2peak = 5.0–2.1 L/min). At rest and during exercise, rectal and mean skin temperatures were measured to calculate the increase in body temperature (ΔT _body) during the trial. Net metabolic heat production (M _NET) and potential heat loss (by means of evaporation, radiation and convection) were calculated. Although subjects exercised at the same relative intensity, ΔT _body presented high between-subjects variability (range from 0.44 to 1.65°C). ΔT _body correlated negatively with body mass (r = −0.49; P < 0.01), body surface area (r = −0.47; P < 0.01) and T_body at rest (r = −0.37; P < 0.05), but it did not significantly correlate with body fatness (r = 0.12; P > 0.05). ΔT _body positively correlated with the body surface area/mass ratio (r = 0.46; P < 0.01) and the difference between M _NET and potential heat loss (r = 0.56; P < 0.01). In conclusion, a large body size (mass and body surface area) is beneficial to reduce ΔT _body during cycling exercise in the heat. However, subjects with higher absolute heat production (more aerobically fit) accumulate more heat because heat production may exceed potential heat loss (uncompensability).     

cAMP-dependent inward rectifier current in neurons of the rat suprachiasmatic nucleus

Electrophysiological properties of the inward rectification of neurons in the rat suprachiasmatic nucleus (SCN) were examined by using the single-electrode voltage-clamp method, in vitro. Inward rectifier current (I _H) was produced by hyperpolarizing step command potentials to membrane potentials negative to approximately −60 mV in nominally zero-Ca²⁺ Krebs solution containing tetrodotoxin (1 μM), tetraethylammonium (40 mM), Cd²⁺ (500 μM) and 4-aminopyridine (1 mM).I _H developed during the hyperpolarizing step command potential with a duration of up to 5 s showing no inactivation with time.I _H was selectively blocked by extracellular Cs⁺ (1 mM). The activation of the H-channel conductance (G _H) ranged between −55 and −120 mV. TheG _H was 80–150 pS (n=4) at the half-activation voltage of −84±7 mV (n=4). The reversal potential ofI _H obtained by instantaneous current voltage (I/V) relations was −41±6mV (n=4); it shifted to −51±8mV (n=3) in low-Na⁺ (20 mM) solution and to −24±4 mV (n=4) in high-K⁺ (20 mM) solution. Forskolin (1–10 μM) produced an inward current and increased the amplitude ofI _H. Forskolin did not change the half-activation voltage ofG _H. 8-Bromo-adenosine 3′,5′-cyclic monophosphate (8-Br-cAMP, 0.1–1 mM) and dibutyryl-cAMP (0.1–1 mM) enhancedI _H. 3-Isobutyl-1-methylxanthine (IBMX, 1 mM) also enhancedI _H. The results suggest that the inward rectifier cation current is regulated by the basal activity of adenylate cyclase in neurons of the rat SCN.     

Ergometry for estimation of mechanical power output in sprinting in humans using a newly developed self-driven treadmill

An evaluation of mechanical power during walking and running in humans was undertaken after developing a specially designed running ergometer (RE) in which the subjects gripped the handlebar in front of them keeping both arms straight and in a horizontal position. Ten subjects participated in comparisons of the mean horizontal pushing force (MF _am) on the handlebar with the mean horizontal ground reaction force (MF _fp) recorded by force platform under the RE during five different constant speeds of walking or running and sprint running with maximal effort. Mechanical power developed during sprint running on the RE was compared with a 50 m sprint. Mean linear velocity (Mv) of the RE belt was recorded by the rotary encoder attached to the axis of the belt. Mean mechanical power calculated from the handlebar setting (MP _am=MF _am × Mv) was compared to that calculated from force platform recordings (MP _fp=MF _fp × Mv). A high test-retest reproducibility was observed for both MF _fp (r=0.889) and MF _am (r=0.783). Larger values for the coefficient of variation for MF _am (11.3%–15.8%) were observed than for MF _fp (3.3%–8.2%). The MP _am, which were obtained from five different constant speeds of walking, running and sprint running were closely correlated to those of MP _fp (y=0.98x − 19.10,r=0.982, P < 0.001). In sprint running, MP _am was 521.7 W (7.67 W · kg⁻¹) and was correlated to the 50 m sprint time (r=−0.683, P < 0.01). It is concluded that the newly developed RE was useful in the estimation of mechanical power output during human locomotion such as when walking, jogging and sprinting. Accepted: 10 October 2000     

Relationship between the curvature constant parameter of the power-duration curve and muscle cross-sectional area of the thigh for cycle ergometry in humans

For high-intensity cycle ergometer exercise, the relationship between power output (P) and its tolerable duration (t) has been well characterized by the hyperbolic relationship: (P–θ _F)·t=W′, where θ_F has been termed the "critical power" or "fatigue threshold". The curvature constant (W′) reflects a constant amount of work which can be performed above θ_F, and it may be regarded as a muscle energy store. The relationship of this energy store to muscle mass is not known. Therefore, the purpose of this study was to determine the relationships among W′, accumulated peak oxygen deficit (accumulated peak O₂-deficit), and muscle cross-sectional area (CSA) of the thigh for high-intensity cycle ergometry in humans. A group of 17 healthy male subjects (aged 21–41 years) participated in this study. The θ_F and W′ of the P-t hyperbolic relationship and the accumulated peak O₂-deficit was calculated by standard procedures. The CSA of muscle, fat and bone in the right thigh were measured using ultrasonography. The mean (SD) of θ_F, W′, accumulated peak O₂-deficit, and muscle CSA of the thigh were 200.0 (17.8) W, 12.60 (2.94) kJ, 2.29 (0.41) l, and 185.3 (22.6) cm², respectively. The muscle CSA of the thigh was positively correlated with W′ (r=0.59, P<0.01) and with accumulated peak O₂-deficit (r=0.54, P<0.05). The relationship between W′ and accumulated peak O₂-deficit also showed a positive correlation (r=0.63, P<0.005). Our results indicated that W′ derived from the P-t hyperbolic curve as anaerobic working capacity is related to the CSA of muscle. Electronic Publication     

Exercise-induced breathing patterns of youth are related to age and intensity

The influences of sex, age, exercise intensity, and end-tidal CO₂ on the inspiratory drive ([V _T kg⁻¹]·T _i ⁻¹) and respiratory timing (T _i·T _tot ⁻¹) components of ventilation were examined in 295 youth (138 females, 157 males); similarly distributed 8–18 years of age. Ventilatory and metabolic measures were collected breath-by-breath at rest and during a slow walk (4.0 km h⁻¹), fast walk (5.6 km h⁻¹) and run (8.0 km h⁻¹). Regression modeling for drive (age, sex, and P_ETCO₂) found that sex was significant (R ² < 0.017; P < 0.05) for rest and running, but not walking. Compared to rest, drive increased by 120% for the slow walk, 217% for the fast walk and 258% for the run (P < 0.0001). Drive decreased with age (P < 0.0001): rest = 0.41 ml kg⁻¹ s⁻¹ year⁻¹; slow walk = 0.90 ml kg⁻¹ s⁻¹ year⁻¹; fast walk = 1.30 ml kg⁻¹ s⁻¹ year⁻¹; and run = 1.47 ml kg⁻¹ s⁻¹ year⁻¹. In the regression models for timing, sex provided ∼ 1% of the variance during the run, but was not significant during rest or walking. Timing increased with exercise intensity by approximately 0.02 units (P < 0.001), but decreased by ∼ 0.002 units year⁻¹ with age for all conditions (P < 0.003). Changes in drive and timing were marginally related to end-tidal CO₂ (exercise R ² < 0.063 for all models). These results suggest that in the control of inspiratory drive and timing during exercise in youth, sex is of minor importance but there are age-related changes which are marginally associated with CO₂.     

Cardiac output and oxygen uptake relationship during physical effort in men and women over 60 years old

This study investigated the relationship between oxygen uptake (VO₂), cardiac output (Q), stroke volume (SV), and heart rate (HR) in 54 men and 77 women (age = 69 ± 5 years) during incremental effort. Subjects performed a maximal cycle-ergometer test and VO₂ was directly measured. HR and SV were assessed by ECG and cardiograph impedance. Regression equations were calculated for Q–VO₂, HR–VO₂, and Q–HR relationships. The equations obtained for women were (a) Q (l min⁻¹) = 2.61 + 4.67 VO₂ (l min⁻¹)(r ² = 0.84); (b) HR (bpm) = 62.03 + 46.55 VO₂ (l min⁻¹) (r ² = 0.72); (c) \textSV \text(ml)=100.6[1- \texte^{-2.6  \textVO₂  (1 \textmin-1)}]{\text{SV}\,{\text{(ml)}}}=100.6[1- {\text{e}}^{-2.6\; {\text{VO}_2}\;{(1\,{\text{min}}^{-1})}}] (r ² = 0.41); (d) HR (bpm) = 41.48 + 9.24 Q (l min⁻¹) (r ² = 0.73). Equations for men were (a) Q (l min⁻¹) = 2.52 + 5.70 VO₂ (l min⁻¹) (r ² = 0.89); (b) HR (bpm) = 66.31 + 32.35 VO₂ (l min⁻¹) (r ² = 0.72); (c) \textSV \text(ml)=143.7[1- \texte^{-1.7  \textVO₂  (1 \textmin-1)}]{\text{SV}\,{\text{(ml)}}}=143.7[1- {\text{e}}^{-1.7\; {\text{VO}_2}\;{(1\,{\text{min}}^{-1})}}] (r ² = 0.47); (d) HR (bpm) = 56.33 + 5.25 Q (l min⁻¹) (r ² = 0.69). The intercepts for Q–VO₂ and HR–VO₂ equations were similar for both genders, but the slopes were different (P < 0.05). The SV increased from baseline to 50–60% of VO₂ peak in both groups. No gender effect was found in SV increasing pattern, but the absolute values were in general higher for men (P > 0.05). A significant difference between men and women was observed for both slopes and intercepts in the Q–HR relationship (P < 0.05). In conclusion, (a) Q–VO₂ relation was linear during progressive effort; (b) regression intercepts were similar, but the slopes were higher for men compared to women; (c) SV–VO₂ relationship was nonlinear and maximum SV was reached at very submaximal workload; (d) older men exhibited higher Q upward potential as well higher SV but lower HR for a given submaximal workload than women of similar age.     

Aloe spp. – plants with vertebrate-like telomeric sequences

Chromosome termini of most eukaryotes end in tracks of short tandemly repeated GC-rich sequences, the composition of which varies among different groups of organisms. Plant species predominantly contain (TTTAGGG)_n repeats at their telomeres. However, a few plant species, including members of Alliaceae and Aloe spp. (Asphodelaceae) were found to lack such Arabidopsis-type (T₃AG₃)_n telomeric repeats. Recently, it has been proposed that the lack of T₃AG₃ telomeric repeat sequences extends to all species forming the Asparagales clade. Here, we analysed the composition of Aloe telomeres by single-primer PCR and fluorescence in-situ hybridization (FISH) with directly labelled Arabidopsis-type (TTTAGGG)_28–43 DNA probe, and with vertebrate-type (TTAGGG)_33–50 DNA and a (C₃TA₂)₃ peptide nucleic acid (PNA) probe. It was found that Nicotiana tabacum contained Arabidopsis-type telomeric repeats, while Aloe telomeres lacked the corresponding FISH signals. Surprisingly, FISH with the highly specific vertebrate-type (C₃TA₂)₃ PNA probe resulted in strong T₂AG₃-specific FISH signals at the ends of chromosomes of both Aloe and Nicotiana tabacum, suggesting the presence of T₂AG₃ telomeric repeats in these species. FISH with a long (TTAGGG)_33–50 DNA probe also highlighted Aloe chromosome ends, while this probe failed to reveal FISH signals on tobacco chromosomes. These results indicate the presence of vertebrate-like telomeric sequences at the telomeres of Aloe spp. chromosomes. However, single-primer PCR with (T₂AG₃)₅ primers failed to amplify such sequences in Aloe, which could indicate a low copy number of T₂AG₃ repeats at the chromosome ends and/or their co-orientation and interspersion with other repeat types. Our results suggest that telomeres of plant species, which were thought to lack GC-rich repeats, may in fact contain variant repeat types. This revised version was published online in July 2006 with corrections to the Cover Date.     

Relationship between plasma thyroid hormones and some biochemical parameters in Iranian Sarabi calves

The thyroid gland has some important endocrine hormones that regulate basal metabolism in various tissues of domestic animals. Thyroid hormones have a central role in animals’ development and their tissue functions. In this study, the relationship between the plasma thyroxine (T₄), triiodothyronine (T₃), free thyroxine (fT₄), free triiodothyronine (fT₃), triglyceride, cholesterol, glucose, total protein, and albumin concentrations as well as albumin/globulin ratio in different ages of Iranian Sarabi calves was investigated. Blood samples were collected from the jugular vein of 47 clinically healthy calves free from internal and external parasites (grouped according to their age—1–14 days, 1–2, and 3–6 months) in early of winter. The level of thyroid hormones was determined by chemiluminescence, and other parameters were measured by spectrophotometry using commercial kits. Our data from this study indicates that there was no significant difference and correlation in all the studied parameters between age groups and sexes. But we found a significant correlation between plasma T₄ and total protein (P < 0.05, r = 0.600), T₄ and albumin (P < 0.05, r = 0.575), T₃ and fT₃ (P < 0.05, r = 0.610), T₃ and total protein (P < 0.01, r = 0.725), T₃ and glucose (P < 0.01, r = 0.685), and fT₄ and fT₃ (P < 0.05, r = 0.609) concentrations as well as between total protein and albumin/globulin ratio (P < 0.01, r = −0.783).     

Changes in blood content of prostaglandin F2α and leukotrienes C4 and B4 in rats after intravenous injection of contrast agents

It is shown that Triombrast=Hexabrix=Omnipaque≤Melitrast<Ultravist in a dose-independent manner increase the level of prostaglandin F_2α and leukotrienes C₄ and B₄ in the blood of sensitive rats (50%) 15 min after intravenous injection of the preparation, the changes in prostaglandin F_2α being maximal, while those in leukotrienes C₄ minimal. The effect of nonionic contrast agents on the blood level of prostaglandin F_2α (0.1–2.0 g I/kg, except for Omnipaque) and leukotriene B₄ (in a dose of 0.5 g I/kg) is more pronounced in comparison with the ionic preparations. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 289–293, March, 1997     

Effect of monochromatic red and near-infrared light on the adhesive properties of the cell membrane: Dependence on wavelength

Changes in the adhesive properties of the cell membrane after irradiation of HeLa cells with monochromatic visible and near-infrared radiation (λ=580–860 nm, i=1.3 W/m², t=40 sec, D=52 J/m²) are assessed as the number of adherent cells. Three spectral regions (600–625 nm, 645–700 nm, and 720–860 nm) with the maximums near wave-lengths 620, 680, 750, and 825 nm are identified, where the adhesive properties of the cell membrane are observed to be enhanced. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 6, pp. 670–672, June, 1994 Presented by V. P. Solov'ev, Member of the Russian Academy of Medical Sciences     

Prediction of the average skin temperature in warm and hot environments

The prediction of the mean skin temperature used for the Required Sweat Rate index was criticised for not being valid in conditions with high radiation and high humidity. Based on a large database provided by 9 institutes, 1999 data points obtained using steady-state conditions, from 1399 experiments and involving 377 male subjects, were used for the development of a new prediction model. The observed mean skin temperatures ranged from 30.7 °C to 38.6 °C. Experimental conditions included air temperatures (T _a) between 20 and 55 °C, mean radiant temperatures (T _r) up to 145 °C, partial vapour pressures (P _a) from 0.2 to 5.3 kPa, air velocities (v _a) between 0.1 and 2 m/s, and metabolic rates (M) from 102 to 620 W. Rectal temperature (T _re) was included in the models to increase the accuracy of prediction. Separate models were derived for nude (clothing insulation, I_cl, ≤0.2 clo, where 1 clo=0.155 m² · °C · W⁻¹, which is equivalent to the thermal insulation of clothing necessary to maintain a resting subject in comfort in a normally ventilated room, air movement=10 cm/s, at a temperature of 21 °C and a humidity of less than 50%) and clothed (0.6 ≤ I_cl ≤ 1.0 clo) subjects using a multiple linear regression technique with re-sampling (non-parametric bootstrap). The following expressions were obtained for nude and clothed subjects, respectively: T _sk=7.19 + 0.064T _a + 0.061T _r + 0.198P _a− 0.348v _a + 0.616T _re and T _sk=12.17 + 0.020T _a + 0.044T _r + 0.194P _a − 0.253v _a + 0.0029M + 0.513T _re. For the nude and clothed subjects, 83.3% and 81.8%, respectively, of the predicted skin temperatures were within the range of ±1 °C of the observed skin temperatures. It is concluded that the proposed models for the prediction of the mean skin temperature are valid for a wide range of warm and hot ambient conditions in steady-state conditions, including those of high radiation and high humidity. Accepted: 7 February 2000     

Changes in the microheterogeneity of serum α1-acid glycoprotein in pregnancyglycoprotein in pregnancy

Immunodiffusion studies show that serum concentration of α₁-acid glycoprotein remains virtually the same during all trimesters of pregnancy. A positive correlation (r=0.87) between the term of pregnancy and the concentration of the α₁-acid glycoprotein fraction with bi-, tri- and tetra-antenna side chains is established using crossed affine immunoelectrophoresis in the presence of concanavalin A. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 471–474, October, 1996     

Nitric oxide synthase in bronchial epithelium and nitric oxide metabolites in the lungs of rats with bronchial asthma after fenoterol inhalation

Nitric oxide synthase of the bronchial epithelium and concentrations of nitric oxide metabolites (NO₂ ⁻ and NO₃ ⁻) in bronchoalveolar lavage fluids were measured in rats with bronchial asthma after fenoterol inhalation. It was suggested that nitric oxide-ergic mechanisms can mediate the effects of inhaled β₂-adrenergic agonists. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 176–179, August, 2000     

Effect of human defensins on the cytoplasmic Ca2+ content in platelets

The effect of the total fraction of human defensins (HNP-1, HNP-2, and HNP-3) on the cytoplasmic Ca²⁺ content ([Ca²⁺]_i) in the platelets of healthy donors was studied. At concentrations of 0.1–40 μg/ml and an incubation time of 10 min defensins have no effect on [Ca²⁺]_i in platelets labeled with Fura-2AM. However, at higher concentrations (100 μg/ml) they increased platelet [Ca²⁺]_i. In addition, defensins (40 μg/ml) inhibited the Ca²⁺ increase in platelets induced by thrombin, adenosine diphosphate, and the lipopolysaccharide ofS. typhimurium endotoxin. The most pronounced inhibitory effect was observed in a suspension of thrombin-stimulated platelets. It is shown that the effect of human defensins on the functional activity of platelets is due to the alterations in the intracellular Ca²⁺. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 600–603, December, 1994     

Prediction of systemic exposure to cyclosporine in Japanese pediatric patients

The monitoring of the blood concentration at 2 h (C₂) after the oral administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful for the prediction of systemic exposure, the area under the blood concentration–time curve from 0 to 4 h (AUC_0–4), in a group of Japanese patients, consisting of 33 children aged 5–15 years and 19 young adults aged 16–27 years, with a greater correlation for C₂ (r = 0.927) than the trough concentration (r = 0.488). The dose-normalized AUC_0–4 was independent of gender or indications for CsA, while it depended on body size, i.e., the age (P = 0.065) and total body weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072); it was about 22–31% lower in the patients with TT³⁴³⁵. Co-administration of a steroid and further treatment with nifedipine had a more intensive effect (P = 0.018); co-administration resulted in a 51% increase in the dose-normalized AUC_0–4. A strong effect was also observed for the serum total cholesterol level (P = 0.001). Collectively, the discrepancies in the results on MDR1 C3435T among investigators might be due to variability in the age/total body weight, co-administration drugs or serum lipid level.     

Influence of age, sex, and aerobic capacity on forearm and skin blood flow and vascular conductance

This study investigated the influence of age, sex, and aerobic capacity on resting and peak forearm and cutaneous blood flow (FBF, CBF). We recruited 93 female and 129 male subjects (age range 16–76 years). FBF and CBF were assessed by plethysmography and laser-Doppler flowmetry, respectively. Peak FBF was obtained following 5 min forearm vascular occlusion and peak CBF in response to local skin heating of 42°C. Blood pressure was measured manually and by Finapres. Maximal oxygen uptake (VO_2max) was obtained from a treadmill exercise stress test. Age was associated with declines in resting FBF (y = −1.176 ln(x) + 6.6899, r ² = 0.45) and peak FBF (y = −17.21 ln(x) + 93.843, r ² = 0.53) (both p < 0.05). Peak CBF decreased with increasing age (y = −223.6 ln(x) + 1,102.9, r ² = 0.34) (p < 0.05), but resting CBF was unchanged (p > 0.05). Males had higher resting and peak FBF than females (p < 0.05) and these variables were related to ageing better in males (y = −1.245 ln(x) + 7.188, r ² = 0.71 and y = −18.53 ln(x) + 102.82, r ² = 0.69) than in females (y = −1.149 ln(x) + 6.4307, r ² = 0.38 and y = −16.59 ln(x) + 88.872, r ² = 0.55). There were no sex differences in resting CBF (p > 0.05). Peak CBF was much better related to ageing in males than females (y = −276.1 ln(x) + 1,365.4, r ² = 0.53 vs. y = −183.1 ln(x) + 907.86, r ² = 0.28). VO_2max decreased with advancing age and this decline was associated with the decline in peak FBF (y = −0.5933x + 10.91, r ² = 0.36, p < 0.05) but not with peak CBF (p > 0.05). These results suggest that healthy ageing is associated with a curvilinear decline in resting and peak forearm and peak cutaneous vasodilator capacity, with males more severely affected than females. The data indicate that peak FBF is influenced by VO_2max but peak CBF is not.