Association between bone mineral density (DXA), body structure,and body composition in middle‐aged men

The association between bone mass, body structure, and body composition was explored in 156 men, 40 years of AGE . Bone mineral density (total body, lumbar spine, left arm, and left leg) was obtained by dual‐energy X‐ray absorptiometry (DXA; Hologic QDR 4500A). Body structure was determined from a battery of anthropometric dimensions with a principal components analysis. Body composition was estimated with DXA. From the 24 anthropometric dimensions, three components were extracted and identified as muscle, fat, and skeletal length. Significant correlations between the muscle component and all BMD measurements (r = 0.28–0.44) were obtained. Except for BMD of the left arm, which correlated significantly, but negatively, with the fat component (r = ?0.16), no significant relations were found between the fat component and BMD. There were significant correlations between lean mass, fat mass, and BMD measurements. The correlations were higher between lean mass and BMD (r = 0.22–0.44) than between fat mass and BMD (r = 0.08–0.24). The multiple regression analysis revealed that except for BMD of the left arm only lean mass or the muscle component, and not fat mass or the fat component, were independent predictors of BMD. It is concluded that the principal anthropometric determinant of BMD in middle‐aged men is lean mass or muscle. Am. J. Hum. Biol. 14:735–742, 2002. © 2002 Wiley‐Liss, Inc.     

Transport,Uptake, and Metabolism of the Bis(pivaloyloxymethyl)-Ester Prodrug of 9-(2- Phosphonylmethoxyethyl)Adenine in an In Vitro Cell Culture System of the Intestinal Mucosa (Caco-2)

Purpose. To evaluate intestinal transport, uptake and metabolism characteristics of the bis(pivaloyloxymethyl)-ester [bis(POM)-ester] of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine [PMEA]. Methods. Intestinal transport, uptake and metabolism of bis(POM)-PMEA were studied using an in vitro cell culture system of the intestinal mucosa (Caco-2 monolayers). Concentrations of bis(POM)-PMEA and its metabolites mono(POM)-PMEA and PMEA were determined using a reversed-phase HPLC method. Enzymatic stability of bis(POM)-PMEA was evaluated by incubation with purified liver carboxylesterase, homogenates of Caco-2 cells and scraped pig small intestinal mucosa. Results. The use of bis(POM)-PMEA as a prodrug of PMEA resulted in a significant increase in transport of total PMEA [bis(POM)-PMEA, mono(POM)-PMEA and PMEA] across Caco-2 monolayers. While transepithelial transport of PMEA (500 M) was lower than 0.1% during a 3 hr incubation period, transport of total PMEA after addition of bis(POM)-PMEA (100 M) amounted to 8.8% over the same incubation period. Only 23% of the amount transported appeared as intact bis-ester at the basolateral side, while 33% of this amount was free PMEA and 44% was mono(POM)-PMEA, suggesting susceptibility of the prodrug to chemical and enzymatic degradation. Uptake studies revealed that only negligible amounts of bis(POM)-PMEA (< 0.2%) were present inside the cells. Very high intracellular concentrations of PMEA were found 1.2 mM, after a 3 hr incubation with 50 M bis(POM)-PMEA), which suggests that PMEA was trapped inside the cells probably due to its negative charge. This explains that efflux of PMEA was relatively slow (25% of the intracellular amount in 3 hr). Enzymatic degradation of the prodrug by carboxylesterase was confirmed by incubation of bis(POM)-PMEA with purified enzyme (K_m = 87 M and V_max = 9.5 M/min). Incubation of bis(POM)-PMEA (10 M) with cell homogenate of Caco-2 monolayers and pig small intestinal mucosa produced similar degradation profiles. Conclusions. The use of the bis(POM)-prodrug significantly enhances the intestinal permeability of PMEA. Intracellular trapping of PMEA in the intestinal mucosa may result in slow release of PMEA to the circulation after oral administration of bis(POM)-PMEA.     

In Vivo Evaluation of a Colon-Specific Drug Delivery System: An Absorption Study of Theophylline from Capsules Coated with Azo Polymers in Rats

Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coatings for colon-specific drug delivery. The gastrointestinal absorption of theophylline from capsules coated with the azo polymers was examined in the proximal part of the small intestine and the cecum of male Wistar rats. The capsules were surgically inserted in the region of interest. The plasma concentration of the drug was higher when the capsules were inserted in the cecum as compared to the small intestine. The appearance of theophylline in the plasma when capsules were administered in the small intestine can be attributed to simple diffusion of the drug through the swollen polymer coating. Release and absorption from the cecum is the combined result of diffusion and degradation of the azo polymer coatings by bacterial azo reductase.     

Multilevel modelling of longitudinal changes in isokinetic knee extensor and flexor strength in adolescent soccer players

The purpose of the study was to model the longitudinal development of knee extension (KE) and flexion (KF) strength in adolescent soccer players. A mixed-longitudinal sample composed of 67 soccer players aged 11.0–13.9?years at baseline was followed on three-to-five occasions over 5 years. Stature, body mass and several skinfold thicknesses were measured. Fat mass was estimated from skinfolds and fat-free mass (FFM) derived. Skeletal age was estimated with the TW2-RUS protocol. An isokinetic dynamometer was used to obtain peak torque of KE and KF from concentric assessments at an angular velocity of 180°/s. Multilevel random effects regression analyses were performed. Among youth soccer players aged 11–16?years, isokinetic strength of the knee muscle groups was reasonably predicted from chronological age (CA), stature and FFM: KE?=?–66.170?+?5.353?×?(CA)?+?0.594?×?(CA²)?+?0.552?×?(stature)?+?1.414?×?(FFM), and KF?=?–9.356?+?2.708?×?(CA)?+?1.552?×?(FFM). In conclusion, CA per se accounted for annual increments of 5.4?Nm in KE and 2.7?Nm in KF.     

Nasal absorption enhancement strategies for therapeutic peptides: an in vitro study using cultured human nasal epithelium

This study examined the potential usefulness of cultured human nasal epithelium as a model to investigate nasal absorption enhancement strategies for therapeutic peptides. The transport of leucine enkephalin (Leu-Enk) in the presence of bestatin and puromycin, respectively and various combinations of these protease inhibitors with absorption enhancers capable of inhibiting proteases or protecting peptides against protease degradation (glycocholate, dimethyl-beta-cyclodextrin (DM beta CD)) was studied. Epithelial membrane perturbation, protein leakage, bestatin/puromycin absorption and rebound aminopeptidase activity were used as toxicological end-points. The combination of puromycin with glycocholate or DM beta CD resulted in a higher absorption enhancement of Leu-Enk (9-14%) than when the absorption enhancers were combined with bestatin (1-3%) or when the inhibitors were used alone (2-4%). The higher absorption enhancement resulting from the combination of protease inhibitors with absorption enhancers caused a significant reduction of epithelial resistance and increased sodium fluorescein transport. Although only puromycin permeated the human nasal epithelium, both protease inhibitors induced a significant rebound aminopeptidase activity (25-61%), which can be associated with protein leakage (21-46%). This study highlighted (i) the potential usefulness of cultured human nasal epithelium as a model to study nasal absorption enhancement of therapeutic peptides; (ii) further studies using in vivo nasal models are required to ascertain whether the membrane perturbation and cytotoxicity observed with various combinations of the protease inhibitors and absorption enhancers really raise safety concerns.     

Characterization of human nasal primary culture systems to investigate peptide metabolism

The objectives of this study were to validate and compare the suitability of different primary cell culture systems as models to investigate peptide enzymatic stability following nasal administration. The degradation kinetics of a model peptide, leucine enkephalin (Tyr-Gly-Gly-Phe-Leu, Leu-Enk), was determined in four nasal cell culture systems: immersion, air-liquid interface, sequential monolayer-suspension, floating collagen. The influence of enzyme inhibitors (bestatin, puromycin) and Leu-Enk metabolite analogs (Tyr-Gly, Phe-Leu, Tyr-Gly-Gly, Gly-Phe-Leu) on the Leu-Enk degradation profile was also investigated. The disappearance of Leu-Enk in all the cell culture systems followed first order kinetics. The specific activity in the cell culture systems followed the rank: sequential monolayer-suspension (32.60 microM min(-1) mg(-1)) >air-liquid interface (15.19 microM min(-1) mg(-1)) >immersion (11.49 microM min(-1) mg(-1)) >floating collagen (4.57 microM min(-1) mg(-1)). At equimolar concentration, bestatin had a higher inhibitory effect than puromycin. The rate of hydrolysis of Leu-Enk was reduced significantly by co-incubation with Leu-Enk metabolite analogs. This study showed that immersion, sequential monolayer-suspension and air-liquid interface culture systems may be potentially suitable for further studies on peptide enzymatic stability following nasal administration.     

Adolescent growth spurts in female gymnasts

OBJECTIVES: Three questions were addressed: (1) Do female gymnasts have adolescent growth spurts in height, sitting height, and leg length? (2) Are the sequence and magnitude of spurts comparable with female adolescent non-athletes? (3) How do the data compare with other female gymnasts and with short girls? STUDY DESIGN: Height and sitting height were measured annually on 15 Belgian gymnasts from 8.7 +/- 1.5 to 15.5 +/- 1.5 years. The gymnasts trained, on average, approximately 15 h/wk. Leg length was estimated as height minus sitting height. The Preece-Baines Model I was fitted to individual growth records to estimate ages at peak velocity and peak velocities for the three dimensions. Age at menarche and skeletal age were also assessed. RESULTS: Gymnasts have clearly defined adolescent spurts in height, estimated leg length, and sitting height that occur approximately 1 year later and are slightly less intense than in nonathletic adolescent girls. Age at menarche and skeletal age are consistent with later somatic maturation. The pattern of adolescent growth and maturation is similar to that of other gymnasts, short normal late-maturing girls, and late-maturing girls with short parents. CONCLUSIONS: The results emphasize a primary role for constitutional factors in the selection process of female gymnasts at relatively young ages.     

Optimized 3D virtually planned intermediate splints for bimaxillary orthognathic surgery: A clinical validation study in 20 patients

Orthognathic surgery is indicated for the treatment of significant skeletal malocclusions and facial dysmorphosis. Recent technological developments allow surgeons to virtually plan the orthognathic jaw movements. When producing intermediate splints, overlap between the upper and lower dentitions can occur. Autorotation of the mandible is often used as a solution for this problem. The purpose of this study was to present an optimized approach to fabricate digital intermediate splints based on the use of a scanned thick wax bite to overcome dental overlap during planning.Twenty patients (9 males and 11 females) undergoing bimaxillary orthognathic surgery participated in this prospective study. Planning of the maxillary movements was conducted by the same surgeon. The thick wax bite was scanned using an intraoral scanner and a special CBCT protocol. The fabrication of the intermediate splints was done by means of conventional model surgery and virtual 3D planning-printing. The splints were clinically assessed by comparing the digitally printed intermediate splints to the corresponding conventional set-up which served as the clinical standard. Moreover, reproducibility and comparison tests between the scanned wax bites were implemented.The root mean square (RMS) for the reproducibility and comparison tests was respectively 0,15 mm (SD 0,24 mm) and 0,19 mm (SD 0,08 mm). 19 out of the 20 intermediate digitally 3D printed splints were clinically accepted.This proposed protocol can be considered as an optimization to the current 3D planning protocols of bimaxillary orthognathic surgery.     

Longitudinal Study of Repeated Sprint Performance in Youth Soccer Players of Contrasting Skeletal Maturity Status

The purpose of the study was to evaluate the developmental changes in performance in a repeated-sprint ability (RSA) test in young soccer players of contrasting maturity status. A total of 83 regional level Portuguese youth soccer players, aged 11-13 years at baseline was assessed annually. Stature, body mass, 7x34.2-m sprint protocol (25-s active recovery), 20-m multi-stage continuous shuttle endurance run and counter-movement jump (CMJ) without the use of the arms were measured. Fat-free mass (FFM) was determined by age and gender-specific formulas. Developmental changes in total sprint time across ages were predicted using multilevel modeling. Corresponding measurements were performed on an independent cross-sectional subsample of 52 youth soccer players 11-17 years to evaluate the predictive model. CA, CA², maturational status (SA-CA), body size (mass and stature), FFM, aerobic endurance, lower limb explosive strength and annual volume training significantly improved the statistical fit of the RSA multilevel model. In ‘late’ maturing athletes, the best model for predicting change in RSA was expressed by the following equation: 86.54 - 2.87 x CA + 0.05 x CA² - 0.25 x FFM + 0.15 x body mass + 0.05 x stature - 0.05 x aerobic endurance - 0.09 x lower limb explosive strength - 0.01 x annual volume training. The best fitting models for players who were ‘on time’ and ‘early’ maturing were identical to the best model for late maturing players, less 0.64 seconds and 1.74 seconds, respectively. Multilevel modeling provided performance curves that permitted the prediction of individual RSA performance across adolescent years in regional level soccer players.

Key points

• Repeated-sprint ability tests are a valuable sport-specific field test of sprint performance in youth soccer players. Here, the test had reasonable reliability and can be useful to trainers and coaches in the assessment of young athletes and in monitoring changes over time.
• The total sprint time of youth soccer players advanced in biological maturation improves more, on average, than that of players who are on time (average) and late in maturation. The performance difference between early and late maturing players is consistent after about 13 years of age.
• Multilevel modeling is a promising statistical technique for analyzing the development of functional capacity in a sport. It has the potential to provide useful information to assist trainers and coaches in evaluating and facilitating the development of individual players.

Key words: young athletes, multilevel modeling, growth, maturation, short-term effort