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Biomedical subjects

G de Groot

Publications and source records attributed to G de Groot.

At least 37 records · Page 2Linked to original sources

Supramaximal cycle tests do not detect seasonal progression in performance in groups of elite speed skaters.

Seven female and eight male elite junior skaters performed cycle ergometer tests at four different times during the 1987/1988 season. The tests consisted of a Wingate-type 30-s sprint test and a 2.5-min supramaximal test. The subjects were tested in February, May and September 1987 and in January 1988. Maximal oxygen consumption was measured during the 2.5-min test. With the exception of the maximal oxygen consumption of the women in May which was about 6% lower than in the other three tests, no seasonal changes in the test results could be observed--this, in spite of a distinct increase in training volume (from 10 to more than 20 h.week-1) and training intensity in the course of the season. When the test data were compared to those of elite senior skaters, it appeared that the junior skaters showed the same values for mean power output during the sprint test [14.2 (SD 0.4) W.kg-1 for the men and 12.6 (SD 0.5) W.kg-1 for the women] and maximal oxygen consumption [63.1 (SD 2.8) ml.kg-1.min-1 for the men and 55.3 (SD 3.5) ml.kg-1.min-1 for the women, respectively] as found for senior skaters. It seemed, therefore, that the effects of training in these skaters had already levelled off in the period before they participated in this investigation. In contrast to previous studies, no relationship could be shown between the test results and skating performance. This was most likely due to the homogenous character of the groups (mean standard deviations in power and oxygen consumption were only 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ice friction during speed skating.

During speed skating, the external power output delivered by the athlete is predominantly used to overcome the air and ice frictional forces. Special skates were developed and used to measure the ice frictional forces during actual speed skating. The mean coefficients of friction for the straights and curves were, respectively, 0.0046 and 0.0059. The minimum value of the coefficient of ice friction was measured at an ice surface temperature of about -7 degrees C. It was found that the coefficient of friction increases with increasing speed. In the literature, it is suggested that the relatively low friction in skating results from a thin film of liquid water on the ice surface. Theories about the presence of water between the rubbing surfaces are focused on the formation of water by pressure-melting, melting due to frictional heating and on the 'liquid-like' properties of the ice surface. From our measurements and calculations, it is concluded that the liquid-like surface properties of ice seem to be a reasonable explanation for the low friction during speed skating.

Biomechanical Phenomena↗

A power equation for the sprint in speed skating.

An analysis of the start of the 500 m speed skating races during the 1988 Olympic Winter Games showed a remarkably high correlation between the acceleration of the skater in the first second of the sprint and the final time (r = -0.75). In this study a power equation is used to explain this high coefficient of correlation. The performance in speed skating is determined by the capability of external power production by the speed skater. This power is necessary to overcome the air and ice friction and to increase the kinetic energy of the skater. Numerical values of the power dissipated to air and ice friction, both dependent on speed, are obtained from ice friction and wind tunnel experiments. Using aerobic and anaerobic power production as measured during supra maximal bicycle tests of international-level speed skaters, a model of the kinetics of power production is obtained. Simulation of power production and power dissipation yields values of speed and acceleration and, finally, the performance time of the sprint during speed skating. The mean split time at 100 m and the final time at 500 m in these races, derived from simulation, were 10.57 s (+/- 0.31) and 37.82 s (+/- 0.96), respectively. The coefficient of correlation between the simulated 500 m times and the actual 500 m times was 0.90. From the results of this study it can be concluded that the distribution of the available anaerobic energy is an important factor in the short lasting events. For the same amount of anaerobic energy the better sprinters appear to be able to liberate considerably more energy at the onset of the race than skaters of lower performance level.

Biomechanical Phenomena↗

The constrained control of force and position in multi-joint movements.

In many arm or leg movements the hand or foot has to exert an external force on the environment. Based on an inverse dynamical analysis of cycling, it is shown that the distribution of net moments in the joints needed to control the direction of the external force is often opposite to the direction of joint displacements associated with this task. Kinetic and kinematic data were obtained from five experienced cyclists during ergometer cycling by means of film analysis and pedal force measurement. An inverse dynamic analysis, based on a linked segments model, yielded net joint moments, joint powers and muscle shortening velocities of eight leg muscles. Activation patterns of the muscles were obtained by means of surface electromyography. The results show that the transfer of rotations in hip, knee and ankle joints into the translation of the pedal is constrained by conflicting requirements. This occurs between the joint moments necessary to contribute to joint power and the moments necessary to establish a direction of the force on the pedal which allows this force to do work on the pedal. Co-activation of mono-articular agonists and their bi-articular antagonists appear to provide a unique solution for these conflicting requirements: bi-articular muscles appear to be able to control the desired direction of the external force on the pedal by adjusting the relative distribution of net moments over the joints while mono-articular muscles appear to be primarily activated when they are in the position to shorten and thus to contribute to positive work. Examples are given to illustrate the universal nature of this constrained control of force (external) and position (joint). Based on this study and published data it is suggested that different processes may underlie the organization of the control of mono- and bi-articular muscles.

Adult↗

The distribution of anaerobic energy in 1000 and 4000 metre cycling bouts.

In sprinting events of short duration, performance depends not only on the mean external power output and the frictional losses but also on the distribution of energy over the race. To investigate the optimal distribution of anaerobic energy during cycling the 1000 m time trial and the 4000 m pursuit, we simulated a power equation which contains expressions for the production of aerobic and anaerobic power, for frictional losses and for the rate of change of kinetic energy. Parameters for air- and rolling resistance were derived from the literature and the equations for aerobic and anaerobic power production were based on supra-maximal bicycle ergometer tests. Simulated lap and final times were compared to those realized by the best four athletes during the 1990 World Championships. The mean final times of these athletes of 64.1 s and 272.6 s for the 1000 m and 4000 m respectively were closely approximated by the simulated times of 63.7 s and 281.3 s. The simulations show that performance in the 1000 m race depends to a great extent on a large power output at the onset of the race. Moreover, it is demonstrated that this distance should be cycled in an all out fashion and not with a uniform velocity after the start despite the higher air frictional losses. For the 4000 m pursuit it appears to be more effective to perform a short but powerful start and then continue the race with a constant or only slightly decreasing power output.

Bicycling↗

Intoxication with beta-sympathicolytics.

Based on the review of available literature, this article states the possible clinical problems with beta-blocker intoxication. Some 26% of severe cases of intoxication will die. This fact stimulated the attempt, using animal experiments, to gain an insight into the pathophysiological profile of this intoxication. The results of these animal experiments led to the following conclusion: toxic doses of beta-blockers result in a dose-dependent decrease of myocardial contractility. This negative inotropic effect is not related to the antagonizing effects of the beta-blocker at the beta-adrenergic receptor level, nor to the additional properties of this group of drugs, but is influenced by a combination of other factors. These include (1) a direct negative inotropic effect on the myocardium, probably caused by a calcium dependent mechanism; (2) a decrease in serum calcium concentration, probably caused by a decreased parathormone production; (3) a centrally mediated hypotensive action. Toxic doses of beta-blockers do not only affect the myocardium and the haemodynamic system, they can also lead to respiratory arrest. This arrest is caused by the direct effect of these drugs on the central nervous system and can, in itself, be the cause of death. Such results lead to the following therapeutic advice: patients with severe beta-blocker intoxication must be admitted to an Intensive Care Unit, as early initiation of ventilation, as well as administration of beta-antagonist can be essential; the drop in serum calcium concentration must be corrected; drugs which can improve myocardial contractility, other than via the beta-adrenergic receptor, such as phosphodiesterase inhibitors and glucagon, should be administered.

Adrenergic beta-Antagonists↗

Coordination of leg muscles during speed skating.

Five speed skaters of elite performance level and six speed skaters of trained level were subjected to an inverse dynamical analysis during speed skating. Push-off forces were registered by means of special skates. Myoelectric activity (EMG) of ten leg muscles and cinematographic data were recorded. Linked segment modelling yielded net joint moments and joint powers. The speed skating technique is characterized by a typical horizontal position of the trunk and a suppression of a plantar flexion during the push-off. This technique, necessary to reduce external friction, constrains the transfer of rotation in joints to translation of the mass center of the body. In spite of constrained push-off, the EMG levels of the leg muscles show a proximo-distal temporal order which to a certain extent is comparable to that previously found in an unconstrained vertical jump. This proximo-distal sequence is also reflected by the time courses of the net moment and net power output in hip, knee and ankle joints. The temporal sequence in activation levels of activated muscles is not different between elite and trained speed skaters. The difference in performance level between these groups obviously has an origin in the ability of the elite speed skaters to realise larger net joint moments. Differences in net joint moments and in kinematics result in a higher power output and a lower air frictional force for the elite than for the trained speed skaters.

Adult↗

Differences in the duration of sedative and anxiolytic effects of desmethyldiazepam in two outbred Wistar strains.

Different sensitivities to benzodiazepines have been described for various strains of both rats and mice suggesting that variations in biological features of the animals are responsible for these differences. Since all reports concern inbred strains, we studied two outbred Wistar strains which are used routinely in several research disciplines. The pharmacodynamics of desmethyldiazepam (DMD), the main active metabolite of diazepam in man, were compared for male rats of the Riv:TOX strain (from the National Institute of Public Health and Environmental Protection) and the Crl:(WI)BR strain. The duration of sedative action of DMD after oral administration, as derived from suppression of the nocturnal locomotor activity, was longer in the Riv:TOX strain than in the Crl:(WI)BR strain. Accordingly, suppression of novelty-induced corticosterone release as an index of anxiolytic action was observed 11 hours after DMD administration in Riv:TOX rats but not in Crl:(WI)BR rats. At that time, serum DMD concentration was shown to be higher in the Riv:TOX strain than in the Crl:(WI)BR strain. The data are discussed in relation with possible metabolic differences between the two strains.

Animals↗

31P NMR study of cisplatin- and doxorubicin-induced changes in tumour metabolism in rats with a cisplatin-sensitive or -resistant immunocytoma.

The response of tumours to treatment with the cytostatic drugs cisplatin (CDDP) or doxorubicin (DXR) was followed in vivo by 31P NMR spectroscopy. A CDDP-sensitive parent line (IgM-I) and a CDDP-resistant subline (IgM/CDDP) of the IgM-immunocytoma grown s.c. on LOU/M WsL rats were used. Animals from both tumour groups (n = 33) were divided into 3 subgroups: CDDP-treated (1 mg/kg), DXR-treated (10 mg/kg) and control. In 3 out of the 4 treated subgroups where the tumours regressed to less than one half of the initial size, 31P NMR spectroscopy revealed alkaline shifts of 0.31-0.41 pH units at day 4, while the ratio of nucleoside triphosphate to Pi in the tumours, increased continuously to 250-435%. Following CDDP treatment, the 31P NMR spectra of the non-responding IgM/CDDP tumours showed a similar pH increase (0.37 units). The ratio of NTP/Pi showed a temporary decrease to 63 +/- 14% SEM at day 1, which was followed by a recovery to 130 +/- 12% at day 2 and 119 +/- 15% at day 4. The control tumours showed no change in pH and a gradual decrease in the ratio of NTP/Pi. In DXR-treated rats the concentrations of DXR in the immunocytoma tumour and its subline were similar, but in the CDDP-treated rats the IgM-I tumours contained significantly higher levels of platinum than the IgM/CDDP tumours, both measured at 3 and 4 days after administration. The continuous increase in NTP/Pi ratio observed in the responding tumours, is a phenomenon characteristic of tumour regression, while the early temporary decrease in tumour NTP/Pi ratio could be associated with resistance to CDDP. Whether the reported response-specific spectral change applies to other tumour types and other treatment regimens remains to be established.

Animals↗

Determination and interpretation of mechanical power in human movement: application to ergometer cycling.

Based on a model consisting of three rigid links, an instantaneous power equation has been deduced for ergometer cycling which shows a causal relationship between power liberated in joint rotation on the one hand and the rate of change of segmental energy plus the power transferred to the pedal on the other. The shape and magnitude of these two types of power have been calculated by measurements of pedal force and cinematographic analysis and the results show fair agreement between them. When cycling at a mean exercise intensity of 340 W at 90 rpm, less than 28 W appears to be lost in the (necessary) changes of segmental energies. It is suggested that power liberated in the joints should be judged as the source of power in the power equation. It is, therefore, proposed that this power should be defined as external power in this and other human movement.

Exercise↗

Two cases of acute toluene intoxication.

Two patients exposed to high concentrations of toluene in air (greater than 7000 mg/m3) were found at the bottom of a small swimming pool under construction. Their symptoms were stupefaction, paresis, and amnesia. Patient A had been exposed for three hours and patient B for two hours. Ninety minutes after the exposure, the toluene blood concentration in patient A was 4.1 mg/l and in patient B 2.2 mg/l. Urinary ortho-cresol secretion was shown to be a good index of exposure to toluene. After high level exposure, urinary meta-cresol excretion may also be used to monitor toluene exposure.

Acute Disease↗

A simulation of speed skating performances based on a power equation.

Using kinetics of aerobic and anaerobic power production as measured during supramaximal bicycle tests of five speed skaters of international level, a model of the kinetics of power production during skating is obtained. Velocity time courses of a generalized speed skater were calculated for all Olympic distances (500 m, 1000 m, 1500 m, 5000 m, and 10,000 m) by means of simulation of an equation of produced power, power dissipated to air and ice friction, and rate of change of kinetic energy of the skater. Different strategies of distribution of anaerobic energy during a race were compared. With a single equation it appeared to be possible to simulate the mean split and final times of the five distances realized during the Winter Olympics 1988 within an error which does not exceed 1.6% (mean error in final times: 0.8%). The results show that a fast acceleration (high initial power output) is crucial for the sprinting events (500 m and 1000 m). It is shown that this initial power output level is even more important than the total amount of energy available for a 500 m and 1000 m race. For the long distances the simulations show that skaters should combine a fast but short lasting start with a constant power output following the start in order to minimize air frictional losses.

Body Weight↗

Platinum concentrations and DNA adduct levels in tumors and organs of cisplatin-treated LOU/M rats inoculated with cisplatin-sensitive or -resistant immunoglobulin M immunocytoma.

Female LOU/M rats, bearing either a cisplatin (cisDDP)-sensitive or -resistant IgM immunocytoma, were sacrificed at 1 or 24 h after cisDDP administration (i.v., 10 mg/kg of body weight). Platinum levels, determined with atomic absorption spectroscopy, were in the order kidney much greater than liver greater than tumor greater than spleen in the 1-h samples. In the 24-h samples, more platinum was found in spleens than in tumors; the levels in the kidneys were the same as those measured at 1 h, in the spleens they were higher, and in livers and tumors they were lower than at 1 h after the injection; the greatest decrease occurred in the resistant tumor. cisDDP-DNA adducts were detected after chromatography of digested DNA samples isolated from these tissues and from blood cells. The quantitation of the four cisDDP-DNA adducts (Pt-G, Pt-AG, Pt-GG, G-Pt-G, the same as found previously in cisDDP-reacted DNA) was performed with specific antibodies, in the competitive enzyme-linked immunosorbent assay. The cisDDP-DNA adduct levels in the various 1-h tissue samples showed the same ranking order as the platinum levels. The blood samples contained the lowest amount of adducts. Because of the high platinum level in the kidneys (26 mg/kg of wet tissue), the adducts in this organ also could be determined with atomic absorption spectroscopy (the four adducts comprised about 400 fmol/micrograms of DNA). Comparison of the atomic absorption spectroscopy and enzyme-linked immunosorbent assay data showed excellent agreement. Except for the kidney, all samples showed a decrease in adduct level between 1 and 24 h after cisDDP treatment. The data on the tumors indicated that the difference in susceptibility to cisDDP between the sensitive and resistant tumors is not due to a decreased platinum content or reduced DNA adduct formation in the resistant tumor.

Animals↗

A comparative study on the antitumor effect, cardiotoxicity and nephrotoxicity of doxorubicin given as a bolus, continuous infusion or entrapped in liposomes in the Lou/M Wsl rat.

Liposome encapsulation of doxorubicin (DXR) has been shown to increase the therapeutic index of the drug in several animal systems. The prevention of peak plasma concentrations of free drug might be a major factor contributing to the beneficial effects resulting from liposome encapsulation. If so, the administration of DXR as a continuous infusion should also lead to an improved therapeutic index. In the present paper, the administration of liposome-encapsulated DXR is compared with the infusion of DXR with regard to their potential to preserve antitumor activity, enhance survival and reduce cardiomyo- and nephropathy in IgM immunocytoma-bearing Lou/M Wsl rats. Plasma concentrations of DXR were determined to correlate the biological results with pharmacokinetic parameters. Liposomes containing phosphatidylcholine, phosphatidylserine and cholesterol (extrusion-multilamellar vesicles) were used. Bolus injections of free DXR (free DXR) and DXR liposomes (lip-DXR) in a multiple-dose regimen were compared with 24-h infusions of the same cumulative doses of DXR (inf-DXR). The antitumor activity of inf-DXR equalled that of free DXR as well as that of lip-DXR at doses of greater than 0.25 mg/kg. The overall survival of tumor-bearing animals treated with 2.0 mg/kg lip-DXR was significantly prolonged (P less than 0.01) in comparison with that of animals treated with 2.0 mg/kg free DXR; however, treatment with 2.0 mg/kg inf-DXR did not induce a significant prolongation of survival. At a cumulative dose of 12 mg/kg, inf-DXR appeared to be as effective as lip-DXR in reducing the severity of cardiomyopathy induced by free DXR. However, for the reduction of nephropathy, only therapy with lip-DXR was effective. Inf-DXR induced high nephropathy scores comparable with those obtained with free DXR. For the first 24 h after an injection of 2.0 mg/kg or after the start of a continuous infusion of 2.0 mg/kg given over 24 h, similar areas under the plasma concentration-time curves (AUC) were calculated for free DXR and inf-DXR. However, for lip-DXR a much higher value was calculated. The higher plasma levels of lip-DXR did not result in higher cardiac levels. After five daily doses of 2.0 mg/kg, a much lower DXR concentration was found in cardiac tissue after the administration of lip-DXR than after the administration of free DXR or inf-DXR. This suggests that an important parameter to be determined and correlated with biological results is the free (i.e. not bound to liposomes) circulating fraction of DXR in lip-DXR-injected animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Improvement of selectivity and sensitivity by column switching in the determination of glycyrrhizin and glycyrrhetic acid in human plasma by high-performance liquid chromatography.

A sensitive method is described for the simultaneous determination of glycyrrhizin and glycyrrhetic acid in human plasma. Quantitation is by high-performance liquid chromatography using ion-pair chromatography on a reversed-phase column. Variable-wavelength ultraviolet detection is employed. For the extraction of both compounds from plasma, a new solid-phase ion-pair extraction procedure using octadecylsilane columns was developed. Because of the strong forces involved in the protein binding of glycyrrhizin, quantitative extraction of this compound from plasma was possible only after an alkaline pH shift. A considerable improvement in selectivity and sensitivity was obtained by automated column switching involving on-line preseparation of the solid-phase extract on a short precolumn and chromatographic analysis of a heart-cut from the precolumn eluate. The limit of detection of both glycyrrhizin and glycyrrhetic acid was 0.1 mg/l in 0.5 ml of plasma. From a preliminary study in human volunteers, it was concluded that glycyrrhetic acid rather than glycyrrhizin is preferred in a study in human volunteers to assess the zero effect level of glycyrrhizin.

Chromatography, High Pressure Liquid↗

Toxicokinetic aspects of thallium poisoning. Methods of treatment by toxin elimination.

The elimination techniques which are used in the treatment of thallium poisoning are evaluated in toxicokinetic perspective. Prussian Blue therapy and forced diuresis are effective in the treatment of acute as well as subacute thallium intoxications. Both elimination techniques can be applied without danger from neurological side effects. Generally, the combined use of these techniques is recommended. Since obstipation as well as renal impairment are common in thallium poisoning, extracorporal elimination techniques are of additional importance. In particular, charcoal haemoperfusion has proven to be successful in the elimination of thallium from the body, especially in the early phase of the intoxication.

Charcoal↗

Resistance and cross-resistance of the IgM immunocytoma in the LOU/M Wsl rat for cisplatin, carboplatin, and iproplatin.

We investigated the antitumor activity of cis-diammine[1,1-cyclobutanedicarboxylato]platinum(II) (CBDCA, JM8) and cis-dichloro-trans-dihydroxybis(isopropylammine)platinum(IV) (CHIP, JM9) for the cis-DDP-sensitive and -resistant IgM immunocytoma in the LOU/M Wsl rat. The optimal dose for the antitumor effect of cis-diamminedichloroplatinum (cis-DDP) in this tumor model is 1 mg/kg body weight. In order to determine the dose range for antitumor activity of JM8 and JM9, tumor-bearing rats were treated i.p. (twice weekly) with 2, 4, 8, 16, or 32 mg/kg JM8 or with 2, 4, or 8 mg/kg JM9. The maximal antitumor activity of JM8 was found at a dose of 4-8 mg/kg and that of JM9, at 4 mg/kg. Doses of 16 or 32 mg/kg JM8 did not increase the antitumor activity. Recurrence of tumors was observed in JM8- and JM9-treated rats. It was demonstrated that these relapses during treatment with JM8 or JM9 involved tumor cell populations almost completely resistant against therapy with the respective drugs. The growth of cis-DDP-resistant tumors was not influenced by the analog JM9 (4 and 8 mg/kg). Only a high dose of JM8 (32 mg/kg) caused growth retardation of the cis-DDP-resistant IgM subline. The JM8-resistant tumor was resistant to treatment with cis-DDP (1 and 2 mg/kg). The JM9-resistant tumor was also resistant to this treatment (1 mg/kg); however, at a dose of 2 mg/kg cis-DDP, growth retardation of the tumor occurred. We conclude that cis-DDP, JM8, and JM9 induce resistance in the IgM immunocytoma tumor system; tumors resistant for cis-DDP were not sensitive to the treatment with JM8 or JM9. Although JM9 reacts in vitro distinctly differently with DNA than cis-DDP and JM8, no differences were found in the induction of Pt resistance. In this study tumor cells were readily made resistant, which allows us to study in more detail the induction of (cross-) resistance by cis-DDP, JM8, and JM9.

Animals↗

Liposomes as drug carrier system for cis-diamminedichloroplatinum (II). II. Antitumor activity in vivo, induction of drug resistance, nephrotoxicity and Pt distribution.

In this study we have investigated the use of liposomes as a drug carrier system for cis-diamminedichloroplatinum(II) (cis-DDP) in order to reduce the nephrotoxicity with preservation of antitumor activity. Liposomes (PC/PS/Chol 10:1:4) were prepared using hydration media containing no or a relatively low concentration of NaCl. It was found that cis-DDP containing liposomes (lip cis-DDP) injected i.v. to IgM immunocytoma-bearing LOU/M rats at a dose of 1 mg cis-DDP/kg (cumulative dose 7 mg cis-DDP/kg) showed less antitumor activity than the free drug. The optimal cumulative dose of free cis-DDP for induction of antitumor activity in this tumor system is 7 mg/kg (7 X 1 mg/kg). At a dose of 2 mg lip cis-DDP/kg (cumulative dose 14 mg cis-DDP/kg) the antitumor activity could not be increased by choosing another phospholipid composition of the liposomes [DPPC/DPPG/Chol (10:1:10)]. cis-DDP incorporated in DPPC/DPPG/Chol liposomes showed a similar antitumor activity to cis-DDP incorporated in PC/PS/Chol liposomes. After an i.v. dose of 2 mg lip cis-DDP/kg (PC/PS/Chol) kidney damage was less compared to the treatment with free cis-DDP (1 mg/kg). However, after a single dose of 2 mg cis-DDP/kg or a cumulative dose of 8 or 16 mg cis-DDP/kg, kidneys of rats treated with lip cis-DDP contained twice as much Pt as after treatment with free cis-DDP. Moreover, after treatment with lip cis-DDP, a twofold increase of the amount of Pt in tumor tissue was measured. In vitro studies with Pt recovered from spleens obtained from rats treated with lip cis-DDP i.v. showed that based on the equal amounts of Pt recovered the antitumor activity of the recovered Pt was reduced, indicating inactivation of cis-DDP in vivo. As during treatment with free cis-DDP, recurrence of the tumor was observed during the continued treatment with lip cis-DDP. It was found that these recurrent tumors were resistant to further therapy with cis-DDP. In conclusion, cis-DDP encapsulation into liposomes decreased the nephrotoxicity. The antitumor activity of cis-DDP is preserved by liposome encapsulation when it was used at a dose of 2 mg/kg, but it was reduced in terms of earlier onset of regrowth.

Animals↗