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1.
Eur J Appl Physiol ; 89(1): 42-52, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12627304

ABSTRACT

The purpose of this study was to investigate effects of concurrent strength and endurance training (SE) (2 plus 2 days a week) versus strength training only (S) (2 days a week) in men [SE: n=11; 38 (5) years, S: n=16; 37 (5) years] over a training period of 21 weeks. The resistance training program addressed both maximal and explosive strength components. EMG, maximal isometric force, 1 RM strength, and rate of force development (RFD) of the leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF) throughout the lengths of 4/15-12/15 (L(f)) of the femur, muscle fibre proportion and areas of types I, IIa, and IIb of the vastus lateralis (VL), and maximal oxygen uptake (VO(2max)) were evaluated. No changes occurred in strength during the 1-week control period, while after the 21-week training period increases of 21% (p<0.001) and 22% (p<0.001), and of 22% (p<0.001) and 21% (p<0.001) took place in the 1RM load and maximal isometric force in S and SE, respectively. Increases of 26% (p<0.05) and 29% (p<0.001) occurred in the maximum iEMG of the VL in S and SE, respectively. The CSA of the QF increased throughout the length of the QF (from 4/15 to 12/15 L(f)) both in S (p<0.05-0.001) and SE (p<0.01-0.001). The mean fibre areas of types I, IIa and IIb increased after the training both in S (p<0.05 and 0.01) and SE (p<0.05 and p<0.01). S showed an increase in RFD (p<0.01), while no change occurred in SE. The average iEMG of the VL during the first 500 ms of the rapid isometric action increased (p<0.05-0.001) only in S. VO(2max) increased by 18.5% (p<0.001) in SE. The present data do not support the concept of the universal nature of the interference effect in strength development and muscle hypertrophy when strength training is performed concurrently with endurance training, and the training volume is diluted by a longer period of time with a low frequency of training. However, the present results suggest that even the low-frequency concurrent strength and endurance training leads to interference in explosive strength development mediated in part by the limitations of rapid voluntary neural activation of the trained muscles.


Subject(s)
Adaptation, Physiological/physiology , Isometric Contraction/physiology , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/physiology , Muscle, Skeletal/physiology , Physical Education and Training/methods , Physical Endurance/physiology , Adult , Exercise , Humans , Knee Joint/cytology , Knee Joint/physiology , Male , Muscle Fibers, Skeletal/classification , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/cytology , Oxygen Consumption/physiology , Physical Fitness/physiology , Stress, Mechanical , Volition/physiology
2.
Bioorg Med Chem ; 9(9): 2365-71, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11553477

ABSTRACT

Novel side-chain diene sulfones 5, analogues of the natural hormone 1alpha,25-dihydroxyvitamin D(3) (calcitriol, 1), were designed to incorporate some of the therapeutically most favorable structural features of the Leo Pharmaceutical Company's drug candidate diene EB 1089 (seocalcitol, 4) and of the Hopkins' non-calcemic side-chain sulfone analogues 2 and 3. Synthesis of diene sulfones 5 features selective Swern oxidation of a primary silyl ether in the presence of a secondary silyl ether (9-->10) and Horner-Wadsworth-Emmons aldehyde addition by a 1-phosphonyl-3-sulfonyl stabilized carbanion regiospecifically at the 1-position to form E,E-diene sulfone 11. Sulfone diene analogue 5a with natural 1alpha,3beta-diol functionality, but not its diastereomer 5b with unnatural A-ring stereochemistry, is antiproliferative in vitro toward murine keratinocytes and malignant melanoma cells, as well as toward MCF-7 human breast cancer cells. Combining diene sulfone 5a with the currently used anticancer drug adriamycin (ADR) caused a noteworthy 3-fold enhancement of ADR antiproliferative potency in MCF-7 cells. Sulfone diene analogue 5a is weakly active transcriptionally in MCF-7 and ROS 17/2.8 cells, binds poorly but measurably to the vitamin D receptor (VDR), and desirably is non-calcemic in vivo at a daily dose (7 days) of 10 microg/kg of rat body weight.


Subject(s)
Antineoplastic Agents/chemical synthesis , Calcitriol/chemical synthesis , Cholecalciferol/analogs & derivatives , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Calcitriol/administration & dosage , Calcitriol/analogs & derivatives , Calcitriol/pharmacology , Cell Division/drug effects , Cholecalciferol/administration & dosage , Cholecalciferol/pharmacology , Dose-Response Relationship, Drug , Doxorubicin/pharmacology , Drug Synergism , Humans , Mice , Rats , Receptors, Calcitriol/metabolism , Structure-Activity Relationship , Sulfones , Transcription, Genetic/drug effects , Tumor Cells, Cultured/drug effects
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