Haemoglobin, haematocrit and red blood cell indices in elite cyclists. Are the control values for blood testing valid?

BACKGROUND: In international cycling and cross-country skiing competitions, blood tests are used to unmask the performance enhancing misuse of erythropoietin. Haematocrit (cycling) and haemoglobin (cross-country skiing) limits have been set by international sporting federations (haematocrit 50%, haemoglobin 18.5 g/dl). Athletes tested above these cut-off values are declared unfit for competition. To investigate the validity of these regulations, we studied haemoglobin, haematocrit and red blood cell indices of elite cyclists before erythropoietin became commercially available. MATERIAL AND METHODS: We investigated 523 blood samples of 92 male elite cyclists (age 16-31 years) from 1978 to 1987. Haematocrit, haemoglobin and red blood cell count were analysed automatically, erythrocyte indices were calculated. RESULTS: Haemoglobin (-0.3 +/- 1 g/dl), haematocrit (-1.2 +/- 2.8%) and red blood cell count (-0.2 +/- 0.4 x 10(6)/mm3) decreased significantly (p < 0.05) with increasing training workload. The erythrocyte indices showed no significant change. Fifty-four blood samples (10.3%) showed a haematocrit above 50%, one sample presented a haemoglobin mass higher than 18.5 g/dl. During periods of increased workload, less athletes tested above the haematocrit limit. CONCLUSION: The current haematocrit limit used in blood tests might lead to a high number of false positive tests.

Evaluation of data produced by optode arrays under flow injection analysis (FIA) conditions using a partial least squares method (PLS2).

Transient diffuse reflectance spectra in the visible wavelength region from an enzyme optode were evaluated to determine artificial mixtures consisting of penicillin and ampicillin simultaneously. In order to achieve a discrimination of the samples the optode operated at two different working pH values. Using an appropriate FIA modus a linear range in the increase and decrease of the time-dependent signal was registered which could be easily fitted by means of ordinary linear regression. In this way characteristic static and dynamic features of the enzyme catalyzed reaction could be extracted for the evaluation by partial least-squares (PLS). The pre-processed raw data were differently weighted and the optimal number of primary factors was each selected by full cross validation. The interpretation of the spectral loadings and the correlation matrix identifies redundant variables resulting in a model with an optimal number of variables. The results obtained with this model show that the straightforward linear regression can be a sufficient approach to avoid the introduction of systematic errors in on-line pre-processing of data.

Application of fuzzy logic in multicomponent analysis by optodes.

Fuzzy logic can be a useful tool for the determination of substrate concentrations applying optode arrays in combination with flow injection analysis, UV-VIS spectroscopy and kinetics. The transient diffuse reflectance spectra in the visible wavelength region from four optodes were evaluated to carry out the simultaneous determination of artificial mixtures of ampicillin and penicillin. The discrimination of the samples was achieved by changing the composition of the receptor gel and working pH. Different algorithms of pre-processing were applied on the data to reduce the spectral information to a few analytic-specific variables. These variables were used to develop the fuzzy model. After calibration the model was validated by an independent test data set.

Synthesis and biological evaluation of naphthyldesferrithiocin iron chelators.

The synthesis and iron-clearing properties of the naphthyldesferrithiocins 2-(2'-hydroxynaphth-1'-yl)-delta2-thiazoline-(4R)-carboxylic acid, 2-(2'-hydroxynaphth-1'-yl)-delta2-thiazoline-(4S)-carboxylic acid, 2-(3'-hydroxynaphth-2'-yl)-delta2-thiazoline-(4R)-carboxylic acid, and 2-(3'-hydroxynaphth-2'-yl)-delta2-thiazoline-(4S)-carboxylic acid are described. While the bile duct-cannulated rat model clearly demonstrates that the 3'-hydroxynaphthyl-2'-yl compounds are orally active iron-clearing agents and the corresponding 2'-hydroxynaphthyl-1'-yl compounds are not, in the primate model none of the benz-fused desazadesferrithiocin analogues are active. Oral versus subcutaneous administration of these ligands strongly suggests that metabolism is a key issue in their iron-clearing properties and that these benz-fused desferrithiocins are not good candidates for orally active iron-clearing drugs.

Simultaneous determination of penicillin and ampicillin by spectral fibre-optical enzyme optodes and multivariate data analysis based on transient signals obtained by flow injection analysis.

A multicomponent detection system using optical biosensors and flow injection analysis is described. The analysis of mixtures containing penicillin and ampicillin was realised by evaluating dynamic measurements of Phenol Red spectra in penicillinase optodes in combination with a diode array spectrometer. A variety of optodes has been produced by changing the composition of the receptor gel and the working pH. A set of characteristic quantities (describing dynamic and static features) could be obtained for each optode. These were used to compare the predictivity of classical multivariate calibration methods as well as of an artificial neural network. In addition, different algorithms were applied for the evaluation of the spectral data in order to select the most appropriate method for feature extraction. In consequence, the information obtained from the multivariate calibration models was used to set up an optimal sensor array consisting of four optodes with different types of penicillinase at different working pH.

An investigation of desferrithiocin metabolism.

The hydrolyses of (S)-desferrithiocin (DFT, 1), (R)-desmethyl-DFT (2), and (R)-desazadesmethyl-DFT (3) were studied at pH 2.5 and 7.2 in order to access the stability of the thiazolines at the pH of the stomach and the serum. At 37 degrees C and pH 2.5, DFT (1) (t1/2 = 18.6 h), desmethyl-DFT (2) (t1/2 = 8.74 h), and desazadesmethyl-DFT (3) (t1/2 = 31.7 h) were shown to open principally to the thiol amides with trace amounts of the corresponding thioesters, < or = 2%. The thiazolines were resistant to hydrolysis at pH 7.2. Iron(III) stabilized significantly the thiazolines in the complexes 16a/b of 3 in regard to hydrolysis at pH 2.5 (t1/2 > 20 days). The iron(III) complexes 16a/b were shown to be stable at pH 7.2. While the thiol amides 13 and 14 of 1 and 2 were isolated from the hydrolysis of the parent desferrithiocins, the thioester 4 and the thiol amide 5 of 3 were synthesized and their stability in aqueous solution, iron-clearance properties, and toxicity were evaluated. Thioester 4 was shown to rearrange to thiol amide 5 at pH 2.5 and 37 degrees C with a half-life of 4.18 h and instantaneously at pH 7.2. Thiol amide 5 is in equilibrium with 4 (5/4 = 49:1) at pH 2.5 and was shown to be stable at pH 7.2. Thioester 4 and thiol amide 5 demonstrated neither iron-clearance activity in iron-overloaded rats nor toxic side effects in mice. Hydrolysis products of the drug, which might be generated in the stomach, seem unlikely to be the source of the drug's toxicity or iron-clearing properties.