Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists

Summary Differences between the effects of training at sea level and at simulated altitude on performance and muscle structural and biochemical properties were investigated in 8 competitive cyclists who trained for 3–4 weeks, 4–5 sessions/week, each session consisting of cycling for 60–90 min continuously and 45–60 min intermittently. Four subjects, the altitude group (AG), trained in a hypobaric chamber (574 torr=2300 m above sea level), and the other four at sea level (SLG). Before and after training work capacity was tested both at simulated altitude (574 torr) and at sea level, by an incremental cycle ergometer test until exhaustion. Work capacity was expressed as total amount of work performed. Venous blood samples were taken during the tests. Leg muscle biopsies were taken at rest before and after the training period. AG exhibited an increase of 33% in both sea level and altitude performance, while SLG increased 22% at sea level and 14% at altitude. Blood lactate concentration at a given submaximal load at altitude was significantly more reduced by training in AG than SLG. Muscle phosphofructokinase (PFK) activity decreased with training in AG but increased in SLG. All AG subjects showed increases in capillary density. In conclusion, work capacity at altitude was increased more by training at altitude than at sea level. Work capacity at sea level was at least as much improved by altitude as by sea level training. The improved work capacity by training at altitude was paralleled by decreased exercise blood lactate concentration, increased capillarization and decreased glycolytic capacity in leg muscle.     

The Bücherer-Strecker synthesis of d- and l-(1-11C)tyrosine and the in vivo study of l-(1-11C)tyrosine in human brain using positron emission tomography

The synthesis of d-and l-(1-¹¹C)tyrosine, starting with ¹¹C-cyanide, is reported. dl-(1-¹¹C)Tyrosine was prepared by the Bücherer-Strecker reaction, from carrier added ¹¹C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure d- and l-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of ¹¹C-cyanide, with a radiochemical yield of d- and l-amino acid of 40%–60%. The d- and l-(1-¹¹C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3–0.5 Ci/mmol and a radiochemical purity better than 99%. The ¹¹C labelled l-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET).     

High exposures to organic solvents among graffiti removers

Summary The exposure to organic solvents among 12 graffiti removers was studied. Health effects were also assessed by structured interview and a symptom questionnaire. Blood and urine samples were collected at the end of the day of air sampling. The concentrations of dichloromethane, glycol ethers, trimethylbenzenes and N-methyl-2-pyrrolidinone in the breathing zone of each worker were measured during one working day. The 8-h time-weighted average exposure to dichloromethane ranged from 18 to 1200 mg/m³. The Swedish Permissible Exposure Limit value for dichloromethane is 120 mg/m3. The air concentrations of glycol ethers, trimethylbenzens and N-methyl-2-pyrrolidinone were low or not detectable. No exposure-related deviations in the serum concentrations of creatinine, aspartate transaminase, alanine transaminase, -glutamyl transpeptidase or hyaluronan or the urine concentrations of ₁-microglobulin, R2-microglobulin or N-acetyl--glucos-aminidase were found. Irritative symptoms of the eyes and upper respiratory tract were more prevalent than in the general population. This study demonstrates that old knowledge about work harzards is not automatically transferred to new professions. Another aspect is that the public is also exposed as the job is performed during daytime in underground stations. At least for short periods, bystanders may be exposed to high concentrations of organic solvent vapours. People with predisposing conditions, e.g. asthmatics, may risk adverse reactions.     

Alphacalcidol oral pulses normalize uremic hyperparathyroidism prior to dialysis

Alphacalcidol oral pulse therapy was given for secondary hyperparathyroidism to 22 children (mean age of 5.6 years) with renal insufficiency. At the beginning of the study, the glomerular filtration rate was <50% of normal, serum intact parathyroid hormone (PTH) was >100 ng/l and the serum phosphate and calcium concentrations were within the normal range. Alphacalcidol (0.5–3.0 g) was given orally thrice weekly in the evening and adjusted according to PTH, ionized calcium and phosphate concentrations. Serum PTH (mean ± SEM) decreased significantly from a pre-treatment level of 393±81 ng/l to 122±34 ng/l after 12 months, and stabilized at this level. Mean vitamin D metabolite concentrations were within the normal range. 1,25-Dihydroxyvitamin D did not increase during therapy, while PTH decreased. The estimated creatinine clearance remained almost unchanged (20±3 and 21±6 ml/min per 1.73 m²). Growth remained low normal (height standard deviation score –1.8±0.3 initially and –1.7±0.4 12 months later) and bone mineral density did not decrease. We concluded that feedback regulation of PTH with oral alphacalcidol pulse therapy is effective in the treatment of hyperparathyroidism in children with renal failure prior to dialysis.     

Pindolol binding to 5-HT1A receptors in the human brain confirmed with positron emission tomography

The augmentation effect of (–)pindolol as used in combination with SSRI to treat major depression has been ascribed to blocking of dorsal raphe nucleus cell body 5-HT autoreceptors. In this study, the radioligand [carbonyl-¹¹C]WAY-100635 and positron emission tomography were used to establish whether pindolol at a clinical dose level (10 mg s.o.d.) occupies 5-HT_1A receptors in the human brain in vivo. Three healthy males were recruited and each subject was used as his own control. The 5-HT_1A receptor occupancy was calculated for the frontal and temporal cortex and the raphe nuclei, using and a ratio analysis with the cerebellar cortex as the reference region. Maximal pindolol plasma concentration was reached within 3 h after drug administration. Two hours after pindolol administration, the regional 5-HT_1A receptor occupancy was within the range 7–21% in the three subjects. The study confirms that the 5-HT_1A-receptor may be a clinically significant target for pindolol. Received: 8 March 1999 / Final version: 15 March 1999     

Selective inhibition of group II phospholipase A2 by quercetin

The influence of quercetin, chlorpromazine, aristolochic acid, and indomethacin on group I phospholipase A₂ (PLA₂) from porcine pancreas and on group II PLA₂ fromVipera russelli was compared. Quercetin and chlorpromazine were found to inhibit PLA₂ activity in lower concentrations (< 100M), while aristolochic acid and indomethacin were inhibitory only in higher concentrations (> 100M). The order of potency againstVipera PLA₂ was: quercetin >chlorpromazin aristolochic acid > indomethacin, while the order of potency against pancreatic PLA₂ was: chlorpromazine > aristolochic acid > indomethacin> quercetin. Thus, quercetin was a potent inhibitor towards group II PLA₂ (IC₅₀=2M), but a very weak inhibitor against group I PLA₂, with maximum 30% inhibition. Aristolochic acid and indomethacin were three to four times more potent towards group II PLA₂ than towards group I PLA₂, while chlorpromazine was equally potent towards the two PLA₂ types. Quercetin and chlorpromazine were also tested against two PLA₂ fractions purified from the plasma of septic shock patients; chlorpromazine was then equally potent towards the two PLA₂ fractions, whereas quercetin was a potent inhibitor of only one of the two PLA₂ fractions (IC₅₀=4M). Together, these results indicate that (1) different PLA₂ inhibitors have different potency depending on which type of PLA₂ they are used against, (2) quercetin selectively inhibits group II PLA₂ and may therefore be used to discriminate between different PLA₂ forms in biological materials, and (3) both PLA₂ of group I and group II are present in septic shock plasma.     

Intracellular uptake and cytotoxic effect in vitro of doxorubicin and epirubicin in human leukemic and normal hematopoietic cells

Summary Leukemic cells from patients presenting with acute nonlymphoblastic leukemia and normal hematopoietic bone marrow cells from healthy donors for allogeneic bone marrow transplantation were incubated for 3 h with doxorubicin and epirubicin at different concentrations. The intracellular uptake at the end of the incubation was determined by photofluorometry in leukemic cells from 15 patients and in normal cells from 9 donors for bone marrow transplantation. Cytotoxicity in vitro against granulocyte/macrophage colony-forming units (CFU-GM) was determined in normal cells from 7 donors, and in vitro toxicity against leukemic cells was determined by a clonogenic technique in cells from 6 patients and by vital dye staining (DiSC) following 4 days' culture in cells from 15 patients. Epirubicin was significantly less toxic than doxorubicin to normal hematopoetic cells (72%±20% survival of cells for epirubicin vs 45%±13% for doxorubicin at a concentration of 0.2 m;P0.005). As analyzed by the DiSC assay, 0.2 m epirubicin was slightly more toxic to leukemic cells than was the same concentration of doxorubicin (47% vs 61% survival,P0.01), but the clonogenic assay revealed no difference in toxicity to leukemic cells. At a concentration of 0.2 m, the mean intracellular uptake of epirubicin in leukemic cells was 0.43±0.26 nmol/mg protein as compared with 0.33±0.14 nmol/mg protein for doxorubicin (not significant). In normal cells, the uptake of epirubicin at a concentration of 0.2 m was 0.47±0.25 nmol/mg protein as compared with 0.31±0.21 nmol/mg protein for doxorubicin (not significant). The reduced myelotoxicity observed in vitro together with the retained toxicity to leukemic cells indicates that the therapeutic index of epirubicin is better than that of doxorubicin.     

Distribution of 5-HT4 receptors in the postmortem human brain--an autoradiographic study using [125I]SB 207710.

The autoradiographic distribution of the 5-HT4 receptor was described using human postmortem brain sections and the selective radioligand [125I]SB 207710 [(1-n-butyl-4-piperidinyl)methyl-8-amino-7-[125I]iodo-1,4-benzodioxane-5-carboxylate]. The specific binding was highest in regions of the basal ganglia (caudate nucleus, putamen, nucleus accumbens, globus pallidus and substantia nigra) and the hippocampal formation (CA1 and subiculum). In the neocortex, the binding showed a distinct lamination pattern with high levels in superficial layers and a band displaying lower levels in deep cortical layers. The results confirm previous studies on the distribution of 5-HT4 receptors in the human brain in vitro and provide high-resolution correlates for in vivo imaging studies using the radioligand recently developed for single photon emission tomography (SPET), [123I]SB 207710.