Impaired glomerular permselectivity for albumin in chemically medullectomized WKY rats

Chemical renal medullectomy with 2-bromo-ethylamine hydrobromide (BEA) has been used to study the importance of the renal medulla in blood pressure regulation. However, conclusive evidence as to whether BEA treatment affects the glomerular barrier is lacking. In the present study, the effects of BEA upon glomerular permselectivity for albumin were studied using isolated kidneys (IPK) perfused at a low temperature (8 °C) to inhibit tubular reabsorption of proteins. Sixteen WKY rats (W_B) received an i.v. injection of BEA (150 mg kg^-1) while 10 rats served as controls (W_C). Volume balance, urinary osmolality and creatinine clearance (GFR) were measured in metabolic cages. Acute paired experiments (n=9) were performed 5–7 weeks after BEA. The rats were anaesthetized and the total in vivo albumin excretion was recorded. The kidneys were then isolated and perfused for measurements of inulin clearance (GFR) and fractional albumin clearance without tubular reabsorption of protein. The nine BEA treated rats showed polyuria and hypoosmotic urine. In vivo GFR was lower in the BEA treated groups when measured with creatinine clearance (459±22 vs. 213±41 μL min^-1 100 g^-1 body wt, P<0.001), while GFR was not significantly changed in the IPK (W_C=135±27, W_B=92±14 μL min^-1 100 g^-1 body wt, n.s.) when perfused at identical pressures. The fractional albumin clearance was increased three times in the BEA group (W_B=9.6±3.4J, P<0.05). Moreover, albumin excretion in vivo was similar in the two groups despite low GFR in the BEA group. We conclude that BEA treatment affects glomerular permselectivity for albumin.     

Endothelin‐1‐induced proliferation of human endothelial cells depends on activation of K+ channels and Ca2+ influx

Aims: Endothelin‐1 (ET‐1) promotes endothelial cell growth. Endothelial cell proliferation involves the activation of Ca²⁺‐activated K⁺ channels. In this study, we investigated whether Ca²⁺‐activated K⁺ channels with big conductance (BK_Ca) contribute to endothelial cell proliferation induced by ET‐1. Methods: The patch‐clamp technique was used to analyse BK_Ca activity in endothelial cells derived from human umbilical cord veins (HUVEC). Endothelial proliferation was examined using cell counts and measuring [³H]‐thymidine incorporation. Changes of intracellular Ca²⁺ levels were examined using fura‐2 fluorescence imaging. Results: Characteristic BK_Ca were identified in cultured HUVEC. Continuous perfusion of HUVEC with 10 nmol L^?1 ET‐1 caused a significant increase of BK_Ca open‐state probability (n = 14; P < 0.05; cell‐attached patches). The ET_B‐receptor antagonist (BQ‐788, 1 μmol L^?1) blocked this effect. Stimulation with Et‐1 (10 nmol L^?1) significantly increased cell growth by 69% (n = 12; P < 0.05). In contrast, the combination of ET‐1 (10 nmol L^?1) and the highly specific BK_Ca blocker iberiotoxin (IBX; 100 nmol L^?1) did not cause a significant increase in endothelial cell growth. Ca²⁺ dependency of ET‐1‐induced proliferation was tested using the intracellular Ca²⁺‐chelator BAPTA (10 μmol L^?1). BAPTA abolished ET‐1 induced proliferation (n = 12; P < 0.01). In addition, ET‐1‐induced HUVEC growth was significantly reduced, if cells were kept in a Ca²⁺‐reduced solution (0.3 mmol L^?1), or by the application of 2 aminoethoxdiphenyl borate (100 μmol L^?1) which blocks hyperpolarization‐induced Ca²⁺ entry (n = 12; P < 0.05). Conclusion: Activation of BK_Ca by ET‐1 requires ET_B‐receptor activation and induces a capacitative Ca²⁺ influx which plays an important role in ET‐1‐mediated endothelial cell proliferation.     

Voluntary drinking and hydration in trained, heat-acclimatized girls exercising in a hot and humid climate

This study examined the effects of beverage composition on the voluntary drinking pattern, body fluid balance and body temperature responses of heat-acclimatized trained girls exercising intermittently in outdoor conditions (WBGT = 30.9 ± 0.2°C). Twelve trained, heat-acclimatized girls (age = 10.6 ± 0.2 years) performed three 3-h sessions, each consisting of four 20-min cycling bouts at 60% VO₂max, alternating with 25-min rest. One of three beverages was assigned: unflavored water (W), flavored water (FW) or flavored water plus 6% carbohydrate and 18 mmol/l NaCl (CNa). Drinking was ad libitum. Total intake was similar among conditions (W = 953.3 ± 107.8 ; FW = 1026.5 ± 138.1; CNa = 906.4 ± 107.5 g). A mild hypohydration occurred during the three conditions (W = −1.12%; FW = −0.95%; CNa = −0.74% BW, P > 0.05). Sweat loss, higher than previously reported for sedentary girls, was not different among conditions (W = 1,051.5 ± 90.8; FW = 979.9 ± 72.8; CNa = 1,052.7 ± 52.6 g). The average amount of urine produced (W = 269.8 ± 85.9; FW = 320.8 ± 87.2; CNa = 85.6 ± 9.3 g) was 73 and 68% higher during FW and W, respectively, compared to CNa (CNa vs. FW, P < 0.05). The increase in rectal temperature, heart rate and all perceptual variables did not differ among conditions. In conclusion, flavoring of the water and addition of 6% carbohydrate plus 18 mmol/l NaCl do not prevent mild hypohydration in trained, heat-acclimatized girls with high sweating rates. However, there is a tendency towards a greater fluid retention with the CNa beverage. An erratum to this article can be found at     

Analysis of ET‐A and ET‐B receptors using an isolated perfused rat lung preparation

Aims and Methods: The pulmonary and vascular effects of endothelin‐1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin‐1 (ET‐1) and the endothelin B (ET_B) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ET_A)‐receptor antagonist FR 139317, the ET_B‐receptor antagonist BQ 788 and the combined ET_A/ET_B‐receptor antagonist Bosentan. The respiratory parameter airway conductance (G_aw) and the vascular parameter perfusion flow were analysed simultaneously. Results: Concentration–response curves for ET‐1 administered intra‐arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET‐1, given as a bolus dose intra‐arterially (100 μL of 0.2 nm ), induced a strong‐ and long‐lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on G_aw or perfusion flow. FR 139317 reduced the effect of ET‐1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET‐1 while G_aw was not influenced. The combined ET_A/ET_B antagonist Bosentan powerfully prevented the ET‐1‐induced decrease in G_aw but did not alter its reduction in perfusion flow. Conclusions: The potent effect of ET‐1 on the vascular side of the lung is mediated mainly through ET_A receptors, whereas both ET_A and ET_B receptors are involved in G_aw in the rat lung.     

Influence of training,sex, age and body mass on the energy cost of running

Summary To highlight the influences of age, sex, body mass (m _b) and running training on the energy cost of running (C _r) young basketball players [38 boys (BB) and 14 girls (BG), aged 14.2 (SD 0.3) and 12.2 (SD 1.9) years, respectively] were selected to be compared to middle-distance runners [27 men (MR) and 14 women (FR) aged 23.7 (SD 3.4) and 23.9 (SD 4.1) years, respectively]. TheC _r was measured during a maximal treadmill test. In each groupC _r and body mass (m _b) and body height were negatively and significantly correlated. A stepwise regression showed that among both the body dimensions measured,m _b was the most important factor in determining the variations ofC _r For the whole group (n=93) the correlation coefficient was 0.72 (P<0.0001). For a givenm _b, there was no significant difference between theC _r of BG, BB and MR: this result would support the hypothesis that the differences inC _r currently attributed to age, running training or sex differences are mainly related tom _b. On the other hand, for a givenm _b, FR showed a significantly lower Cr than the basketball players (P<0.01 for BG and BB) and than MR (P<0.05), thus suggesting that women decrease theirC _r as a response to running training more efficiently than do men.     

Airway inflammation in obese and nonobese patients with difficult-to-treat asthma

Background: Asthma and obesity are associated disorders, but the contribution of obesity to difficult‐to‐treat asthma as well as the mechanisms responsible for this relationship are unclear. The aim of this study was to investigate the relationship between obesity (body mass index ≥ 30) and factors related with asthma severity in patients with difficult‐to‐treat asthma. Methods: One hundred and thirty‐six nonsmoking asthmatic adults with persistent symptoms despite high doses of inhaled or oral corticosteroids and long‐acting bronchodilators were studied [70% female, median (range) age 44.6 (18–75) years, 32% on daily oral corticosteroids]. The association between obesity, lung function parameters [forced expiratory volume in 1 s (FEV₁), functional residual capacity/total lung capacity (FRC/TLC)], inflammatory markers [blood eosinophils, sputum eosinophils and neutrophils, exhaled nitric oxide (FE_NO), airway hyperresponsiveness, C‐reactive protein (CRP)] and aggravating co‐morbid factors (severe chronic sinus disease, gastro‐esophageal reflux, recurrent respiratory infections, psychopathology and obstructive sleep apnea) was investigated. Results: Obese patients (n = 29) had a higher FEV₁%pred (P = 0.05) and a lower FRC/TLC%pred (P < 0.01) compared with nonobese patients (n = 107). Body mass index was inversely related with sputum eosinophils (r = ?0.36, P < 0.01) and FE_NO (r = ?0.30, P < 0.01). Obese patients had an increased risk for gastro‐esophageal reflux (OR = 2.3) and sleep apnea (OR = 3.1). Conclusion: Obesity in patients with difficult‐to‐treat asthma is inversely related with sputum eosinophils and FE_NO, and positively associated with the presence of co‐morbid factors and reduced lung volumes. This suggests that other factors than airway inflammation alone explain the relationship between obesity and asthma severity.     

Down syndrome, autoimmunity and T regulatory cells

Autoimmune diseases are more represented in Down syndrome (DS) individuals compared to chromosomally normal people. Natural T regulatory cells (nT_reg) have been considered to be primary in the role of controlling the intensity and targets of the immune response. We have investigated the phenotypical and functional alteration of nT_reg in a group of DS people. The phenotypical characteristic of T_reg cells of 29 DS was analysed and compared with an age‐matched healthy control group. The inhibitory potential of CD4⁺CD25^highCD127^low T regulatory cells was evaluated on autologous CD4⁺CD25^‐ T cell proliferation in response to activation with a mytogenic pan‐stimulus (anti‐CD2, anti‐CD3 and anti‐CD28 antibodies). The CD4⁺CD25^high cells in the DS and control groups were 2·692 ± 0·3808%, n = 29 and 1·246 ± 0·119, n = 29%, respectively (P = 0.0007), with a percentage of forkhead box protein 3 (FoxP3)‐expressing cells of 79·21 ± 3·376%, n = 29 and 59·75 ± 4·496%, respectively (P = 0.0015). CD4⁺CD25⁺FoxP3⁺ cells were increased in peripheral blood from DS subjects (DS mean 5·231 ± 0·6065% n = 29, control mean 3·076 ± 0·3140% n = 29). The majority of CD4⁺CD25^high were CD127^low and expressed a high percentage of FoxP3 (natural T_reg phenotype). While the proliferative capacity of DS T cells was not altered significantly compared to normal individuals, a reduced inhibitory potential of T_reg compared to healthy controls was clearly observed (mean healthy control inhibition in T_eff : T_reg 1:1 co‐culture: 58·9% ± 4·157%, n = 10 versus mean DS inhibition in T_eff : T_reg 1:1 co‐culture: 39·8 ± 4·788%, n = 10, P = 0.0075; mean healthy control inhibition in T_eff : T_reg 1:0·5 co‐culture: 45·10 ± 5·858%, n = 10 versus DS inhibition in T_eff : T_reg 1:0·5 co‐culture: 24·10 ± 5·517%, n = 10, P = 0.0177). DS people present an over‐expressed peripheral nT_reg population with a defective inhibitory activity that may partially explain the increased frequency of autoimmune disease.     

Effect of nitric oxide and renal nerves on renomedullary haemodynamics in SHR and Wistar rats,studied with laser Doppler technique

The threshold for activation of the humoral renal antihypertensive system, presumably residing in the renomedullary interstitial cells (RIC), is substantially reset upwards in the spontaneously hypertensive rat (SHR). Depressor reactions, normally elicited by an increased renal perfusion pressure, can be inhibited either by high frequency renal nerve stimulation or blockade of nitric oxide synthesis, i.e. manoeuvres decreasing renal blood flow at this high perfusion pressure. The present study was designed to explore the effects on regional renal haemodynamics of blocking NO synthesis with N-ω-nitro-l-arginine (l-NNA) in chloralose anaesthetized SHR and Wistar rats. Mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), cortical blood perfusion (CBP) and papillary blood perfusion (PBP) were measured in renally innervated and denervated SHR (S_in=8, S_dn=8) and in Wistar rats (W_in=10, W_dn=10). An innervated non-treated Wistar group served as control (C_in=12). The laser Doppler technique was used to record CBP and PBP. MAP increased in all groups receiving l-NNA while HR, RBF and CBP simultaneously decreased. The relative decreases in RBF were more marked into the two SHR groups than in the corresponding Wistar groups. After l-NNA PBP also decreased in all four groups despite the increased MAP and more so in the S_i group; W_i -19±8 (P<0.05), W_d -17±6 (P=0.07), S_i -50±9 (P<0.01) and S_d-25±9% (P<0.05). We conclude that NO is important for maintaining PBP especially in SHR. The more marked decrease in PBP in the innervated SHR suggests a NO/renal nerve interaction in the control of renomedullary blood flow in SHR. This finding may be of importance for the regulation of the humoral renal depressor mechanism.     

Genetic Variation in the Peroxisome Proliferator‐Activated Receptor (PPAR) and Peroxisome Proliferator‐Activated Receptor Gamma Co‐activator 1 (PGC1) Gene Families and Type 2 Diabetes

We used a two‐stage study design to evaluate whether variations in the peroxisome proliferator‐activated receptors (PPAR) and the PPAR gamma co‐activator 1 (PGC1) gene families (PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B) are associated with type 2 diabetes (T2D) risk. Stage I used data from a genome‐wide association study (GWAS) from Shanghai, China (1019 T2D cases and 1709 controls) and from a meta‐analysis of data from the Asian Genetic Epidemiology Network for T2D (AGEN‐T2D). Criteria for selection of single nucleotide polymorphisms (SNPs) for stage II were: (1) P < 0.05 in single marker analysis in Shanghai GWAS and P < 0.05 in the meta‐analysis or (2) P < 10^?3 in the meta‐analysis alone and (3) minor allele frequency ≥ 0.10. Nine SNPs from the PGC1 family were assessed in stage II (an independent set of middle‐aged men and women from Shanghai with 1700 T2D cases and 1647 controls). One SNP in PPARGC1B, rs251464, was replicated in stage II (OR = 0.87; 95% CI: 0.77–0.99). Gene‐body mass index (BMI) and gene–exercise interactions and T2D risk were evaluated in a combined dataset (Shanghai GWAS and stage II data: 2719 cases and 3356 controls). One SNP in PPARGC1A, rs12640088, had a significant interaction with BMI. No interactions between the PPARGC1B gene and BMI or exercise were observed.     

Elastomeric Poly(propylene) from “Dual‐side” Metallocenes: Reversible Chain Transfer and its Influence on Polymer Microstructure

Summary: The influence of the cocatalyst nature on the distribution of the stereoerrors along the polymer chain has been studied using either MAO or [(C₆H₅)₃C⁺] [(C₆F₅)₄B^?] to activate a C₁‐symmetric (Flu‐Ind) complex in propene polymerization experiments. The in situ activation with borate indicated the chain back‐skip as the decisive mechanism responsible for stereoerror formation. When MAO is used for activation, additionally the reversible chain transfer to aluminum occurs, which can be called into account as a second mechanism for stereoerror formation. By the combination of ¹³C NMR, DSC, WAXS and SFM, it was shown that the differences in polymerization mechanisms result in variations of stereoerror formation. Due to this, the isotactic block length n_iso as well as their distribution along the chain changes. Using MAO activation, polypropenes with crystallizable blocks consisting of 23–32 monomers in isotactic sequences were generated, which co‐crystallized in α‐ and γ‐phase lamellae. When the reversible chain transfer was occluded (in situ borate activation) the bimodal distribution of crystalline lamellae strongly referred to a homogeneous random distribution of stereoerrors. In this case, two crystalline populations were present. The prevailing one, which crystallized in the orthorhombic γ‐modification, contained 23 consecutive isotactic blocks. Additionally, small amounts of α‐phase lamellae were present consisting of longer isotactic blocks (n_iso > 35). The different crystalline modifications resulted in different polymer morphologies. These changes caused in turn variations in the mechanical properties, such as elasticity and mechanical strength. This clearly shows that, by using different cocatalysts for activating C₁‐symmetric complexes, the properties of poly(propylenes) with statistically distributed stereoerrors can be tailored.

     

The determinants of performance in master swimmers: a cross-sectional study on the age-related changes in propelling efficiency, hydrodynamic position and energy cost of front crawl

The decrease in swimming performance (v _max) that occurs with age is a not only consequence of the physiological decrease in maximal metabolic power ( ${\dot{E}}_{\it max}$ ) but can also be expected to depend on an increase in the energy cost of swimming (C) ${\nu}_{\rm max} = {\dot {E}}_{\rm max}/C.$ In turn, for a given speed and stroke C?=?W _d?/?(η_Pη_o) where W _d is hydrodynamic resistance, η_P is propelling efficiency and η_o is overall efficiency. The aim of this study was to measure C in 47 male masters (31–85?years old) swimming the front crawl at sub-maximal, aerobic, speeds. During the experiments propelling efficiency and projected frontal area (A _eff, an index of W _d) were also determined by kinematic analysis. “Elder” masters (60–80?years) swam at a significantly slower pace (0.65 vs. 0.91?m?s^?1), with a lower η_P (0.23 vs. 0.31) and a larger A _eff (0.39 vs. 0.23?m²) than “younger” masters (30–60?years). No significant differences in C (1.45?kJ?m^?1, on the average) were observed as a function of age or speed, but C values were significantly higher than those assessed in young elite swimmers at the very same speeds; the difference increasing with age with a rate of 0.75?% per year. With the due considerations (in this study the observed changes in η_P, A _eff and C can be either attributed to changes in speed or age) these data confirm the hypothesis that an increase in C contributes to the decrease in swimming performance that occurs with age.     

Association of the CT values of real‐time PCR of viral upper respiratory tract infection with clinical severity,Kenya

Quantitative real‐time polymerase chain reaction (qRT‐PCR) assay of the upper respiratory tract is used increasingly to diagnose lower respiratory tract infections. The cycle threshold (C_T) values of qRT‐PCR are continuous, semi‐quantitative measurements of viral load, although interpretation of diagnostic qRT‐PCR results are often categorized as positive, indeterminate, or negative, obscuring potentially useful clinical interpretation of C_T values. From 2008 to 2010, naso/oropharyngeal swabs were collected from outpatients with influenza‐like illness, inpatients with severe respiratory illness, and asymptomatic controls in rural Kenya. C_T values of positive specimens (i.e., C_T values < 40.0) were compared by clinical severity category for five viruses using Mann–Whitney U‐test and logistic regression. Among children <5 years old we tested with respiratory syncytial virus (RSV), inpatients had lower median C_T values (27.2) than controls (35.8, P = 0.008) and outpatients (34.7, P < 0.001). Among children and older patients infected with influenza virus, outpatients had the lowest median C_T values (29.8 and 24.1, respectively) compared with controls (P = 0.193 for children, P < 0.001 for older participants) and inpatients (P = 0.009 for children, P < 0.001 for older participants). All differences remained significant in logistic regression when controlling for age, days since onset, and coinfection. C_T values were similar for adenovirus, human metapneumovirus, and parainfluenza virus in all severity groups. In conclusion, the C_T values from the qRT‐PCR of upper respiratory tract specimens were associated with clinical severity for some respiratory viruses. J. Med. Virol. 85:924–932, 2013. © 2013 Wiley Periodicals, Inc.     

Statistical methods for assessing linkage disequilibrium at the HLA-A, B, C loci

A number of standard and new statistics for measuring linkage disequilibrium are introduced applicable to any multilocus system. Included are the usual pairwise gametic disequilibrium function, D, the Lewontin disequilibrium index, D_L, a Euclidean disequilibrium distance, D_E, a hierarchy of stratified linkage disequilibrium functions (e.g. a pairwise disequilibrium value conditioned on the value of a third locus) and an averaged conditional disequilibrium expression, D_W. Various global second order measures of disequilibrium are proposed partly based on contingency table statistics and weighted pairwise disequilibrium quantities. A non-parametric (stochastic) comparison assessment for global linkage disequilibrium is also developed. These measures are compared and contrasted at the HLA-A, B, C gene complex for a sample of 2000 haplotypes from a healthy Austrian population. Several results from applying these methods include: (1) Of the various pairwise disequilibrium measures examined, D, D_E and D_W correlated very closely with each other but differ from D_L. (2) The ‘third-order interaction’ between two loci conditional on an allele (or group of alleles) at a third locus indicated that HLA-AB maintains the classical disequilibrium pairings only for conditioning on C_X (the blank allele at locus C), and they mostly disappear for conditioning on C₁ to C₅. (3) Subpopulations involving C₃ or C₄ alleles exhibit the significant new combinations A₃₃B₁₇ and A₂B₁₅. (4) The B, C loci have a higher total linkage disequilibrium than A, B and A, C; more than expected by mapping distance relationships. (5) The total linkage disequilibrium was significantly larger for conditioning on C_X compared to C_X (non-C_X), but smaller for the population conditioned by {C₃, C₄}. A number of interpretations of the results with respect to heterogeneity classifications of populations are discussed.     

Renal endothelin system and excretory function in Wistar-Kyoto and Long-Evans rats

Aim: The role of the kidney endothelin system in the renal regulation of fluid and electrolyte excretion was investigated in Wistar–Kyoto (WKY) and Long–Evans (LE) rats in which we found previously marked differences in the renal excretory responses to endothelin A receptor blockade. Methods: The selective endothelin A and B receptor antagonists BQ‐123 (16.4 nmol kg⁻¹ min⁻¹) and BQ‐788 (25 nmol kg⁻¹ min⁻¹) were infused i.v. for 50 min in conscious chronically instrumented WKY and LE rats and their renal function and renal endothelin system were studied. Results: Without effects on glomerular filtration rate or renal blood flow, BQ‐123 and BQ‐788 decreased by more than 50% (P < 0.01) both urine flow rate and electrolyte excretion in WKY rats but only urine flow rate (P < 0.05) in LE rats. Endothelin‐1 content, preproET‐1/GPDH mRNA ratio, B_max and K_d of total endothelin receptors in renal cortex did not differ between the two strains. In contrast, plasma endothelin‐1 concentration (0.58 ± 0.04 vs. 1.05 ± 0.01 femtomol mL⁻¹; P < 0.01), renal papillary ET‐1 concentration (68 ± 5 vs. 478 ± 62 fmol mg⁻¹ protein; P < 0.01) and preproET‐1/GPDH mRNA ratio (0.65 ± 0.09 vs. 0.88 ± 0.05; P < 0.05) as well as total endothelin receptor number in renal papilla (B_max 5.3 ± 0.4 vs. and 9.0 ± 1.2 pmol mg⁻¹ protein; P < 0.05) were markedly lower in LE than in WKY rats. In vitro studies showed that in both strains ET_B receptors on renal cortical membranes amounted between 65% and 67% and on papillary membranes between 85% and 88%. Conclusion: The present data show that the selective ET_A or ET_B receptor blockade differentially affects tubular water and salt handling, which becomes apparent in conditions of low renal papillary endothelin receptor number and tissue endothelin‐1 concentration.     

Effects of age and gender on the propelling efficiency of the arm stroke

The propelling efficiency of the arm stroke (η _P) was estimated in a group of 63 male and female subjects (9–59 years of age) of good technical skill, swimming the front crawl at sub-maximal speeds. η _P was calculated on the basis of values of speed (v), stroke frequency (SF) and shoulder-to-hand distance (l, calculated from measures of arm length and elbow angle during the in-sweep) as proposed by Zamparo et al. (Eur J Appl Physiol 94:134–144, 2005). In both genders, the distance covered per stroke (Ds = v/SF) is similar before puberty, reaches its maximum at about 20 years of age and then steadily declines. l is significantly larger in males than in females and this difference tended to offset the differences in Ds so that η _P is almost the same in male and female swimmers of the same age group and swimming ability: about 0.31 before puberty, 0.38–0.40 at about 20 years of age and about 0.25 in swimmers older than 40 years of age. The development of η _P and Ds during the life span is similar to the changes in muscle strength and power reported in the literature suggesting that these parameters are related to the ability to exert forceful (and hence effective) strokes in water. Since the energy cost of swimming (C) depends essentially on η _P and the hydrodynamic resistance (W _d), these data further suggest that differences in C between genders are mainly to be attributed to differences in W _d, whereas differences across ages can be attributed also to changes in η _P.     

Optimal power-to-mass ratios when predicting flat and hill-climbing time-trial cycling

The purpose of this article was to establish whether previously reported oxygen-to-mass ratios, used to predict flat and hill-climbing cycling performance, extend to similar power-to-mass ratios incorporating other, often quick and convenient measures of power output recorded in the laboratory [maximum aerobic power (W _MAP), power output at ventilatory threshold (W _VT) and average power output (W _AVG) maintained during a 1 h performance test]. A proportional allometric model was used to predict the optimal power-to-mass ratios associated with cycling speeds during flat and hill-climbing cycling. The optimal models predicting flat time-trial cycling speeds were found to be (W _MAP m ^−0.48)^0.54, (W _VT m ^−0.48)^0.46 and (W _AVG m ^−0.34)^0.58 that explained 69.3, 59.1 and 96.3% of the variance in cycling speeds, respectively. Cross-validation results suggest that, in conjunction with body mass, W _MAP can provide an accurate and independent prediction of time-trial cycling, explaining 94.6% of the variance in cycling speeds with the standard deviation about the regression line, s=0.686 km h⁻¹. Based on these models, there is evidence to support that previously reported -to-mass ratios associated with flat cycling speed extend to other laboratory-recorded measures of power output (i.e. Wm ^−0.32). However, the power-function exponents (0.54, 0.46 and 0.58) would appear to conflict with the assumption that the cyclists’ speeds should be proportional to the cube root (0.33) of power demand/expended, a finding that could be explained by other confounding variables such as bicycle geometry, tractional resistance and/or the presence of a tailwind. The models predicting 6 and 12% hill-climbing cycling speeds were found to be proportional to (W _MAP m ^−0.91)^0.66, revealing a mass exponent, 0.91, that also supports previous research.     

On the 1,4‐cis‐Polymerization of Butadiene with the Highly Active Catalyst Systems Nd(C3H5)2Cl·1.5 THF/Hexaisobutylaluminoxane (HIBAO), Nd(C3H5)Cl2· 2 THF/HIBAO and Nd(C3H5)Cl2·2 THF/Methyl‐aluminoxane (MAO) – Degree of Polymerization,Polydispersity, Kinetics and Catalyst Formation

The allylneodymium chloride complexes Nd(C₃H₅)₂Cl·1.5 THF and Nd(C₃H₅)Cl₂·2 THF can be activated by adding hexaisobutylaluminoxane (HIBAO) or methylaluminoxane (MAO) in a ratio of Al/Nd = 30 for the catalysis of butadiene 1,4‐cis‐polymerization. A turnover frequency (TOF) of about 20 000 mol butadiene/(mol Nd·h) and cis‐selectivity of 95–97% are achieved under standard conditions ([BD]₀ = 2 m, 35°C, toluene). Molecular weight determinations indicate a low polydispersity (M̄_w (LS)/M̄_n (LS) = 1–1.5), the formation of only one polymer chain per neodymium and the linear increase of the degree of polymerization (DP) with the butadiene conversion, as observed for living polymerizations. First indications of chain‐transfer reaction occur only at the highest conversion or degree of polymerization. The rate law r_P = k_P[Nd][C₄H₆]^1.8 is derived for the catalyst system Nd(C₃H₅)₂Cl·1.5 THF/HIBAO and for the system Nd(C₃H₅)Cl₂·2 THF/MAO the rate law r_P = k_P[Nd] [C₄H₆]² with k_P = 3.24 L²/(mol²·s) (at 35°C). Taking into account the Lewis acidity of the alkylaluminoxanes and the characteristic coordination number of 8 for Nd(III) in allyl complexes the formation of an η³‐butenyl‐bis(η⁴‐butadiene)neodymium(III) complex of the composition [Nd(η³‐RC₃H₄)(η⁴‐C₄H₆)₂(X‐{AlOR}_n)₂] is assumed to be a single‐site catalyst for the chain propagation by reaction of the coordinated butadiene via the π‐allyl insertion mechanism and the anti‐cis and syn‐trans correlation to explain the experimental results.     

Genetic effect of single‐nucleotide polymorphisms in the PPARGC1B gene on airway hyperreactivity in asthmatic patients

Background Peroxisome proliferator‐activated receptor gamma coactivator 1 beta (PPARGC1B) is a co‐activator for intracellular receptors such as the estrogen receptor, PPAR, and glucocorticoid receptor, which are involved in asthma development. Objectives Genetic association of single‐nucleotide polymorphisms (SNPs) in the PPARGC1B gene with the risk of asthma and airway hyperreactivity (AHR) was investigated, as well as the functional effects of these SNPs on PPARGC1B gene and protein expression. Methods Direct sequencing of DNA from 24 Korean was performed to identify PPARGC1B SNPs. Genotyping was done in 264 controls and 949 asthmatics using single‐base extension methods. PPARGC1B mRNA levels were measured using real‐time PCR methodology. Luciferase and electrophoretic mobility shift assays (EMSA) were performed to functionally analyse PPARGC1B SNPs on promoter. Results Eighteen SNPs and one insertion/deletion polymorphism were identified, and seven SNPs were genotyped. No significant difference existed in the distribution of SNPs and haplotypes between the asthmatics and controls. However, the allele frequency of ?427C>T and +102525G>A;R265Q showed a significant association with log‐transformed PC₂₀ methacholine values in the asthmatics (P=0.005–0.0004). Real‐time PCR demonstrated higher PPARGC1B mRNA levels in asthmatics having ?427CC allele than in those having ?427TT or CT alleles (P=0.048). The ratio of the mRNA expression for each PPARGC1B exon4‐mRNA compared with the wild type was similar in peripheral blood mononuclear cells carrying the +102525G>A allele. Luciferase reporter assays revealed that ?427C allele caused higher promoter activity than ?427T allele. EMSA demonstrated that ?427C allele exhibited stronger binding activity to a nuclear protein in 293T cells than did the ?427T allele. Conclusions and Clinical Relevance Polymorphisms of ?427C>T on the promoter and those of +102525G>A on exon 5 of the PPARGC1B gene may affect the development of AHR through the modulation of PPARGC1B gene products. The PPARGC1B genotypes may serve as genetic markers for AHR. Cite this as: S.‐H. Lee, A.‐S. Jang, S. Woo Park, J. ‐S. Park, Y. K. Kim, S.‐T. Uh, Y. H. Kim, I. Y. Chung, B.‐L. Park, H. D. Shin and C.‐S. Park, Clinical & Experimental Allergy, 2011 (41) 1533–1544.     

Effect of a 12-month physical conditioning programme on the metabolic cost of walking in healthy older adults

The metabolic cost of walking (C _W) is increased in healthy older adults. Previously, this has been suggested to be associated with age-related decline in physiological/functional factors such as stability and muscle size and strength. Physical training can improve such factors as well as aspects of gait performance in older adults. The aim of this investigation was to determine if it also has a beneficial impact on (lowers) C _W. Thirty-eight community dwelling older adults (aged 70–82 years) assigned to a training group (TRA, n=25) or a control group (CON, n=13) participated in a 12-month intervention. TRA followed a multi-component physical conditioning programme involving supervised resistance, aerobic, and balance exercises twice per week. They also undertook home based exercises once per week. CON carried on with their normal daily activities. C _W and indicators of functional capacity (knee extensor isometric strength, single leg balance time, sit and reach, stand and reach, and 6 min walk distance) were assessed prior to and following the intervention. Significant improvements in knee extensor isometric strength (+21%), single leg balance time (+30%), and 6 min walk distance (+6%) were observed in TRA (P<0.05) but not in CON. However, no change in C _W was observed. In conclusion, this investigation has shown that a multi-component physical conditioning programme had a beneficial impact on functional capacity but did not lower C _W in healthy community dwelling older adults.     

Seasonal and circadian variation in salivary testosterone in rural Bolivian men

Testosterone (T) plays a key role in the increase and maintenance of muscle mass and bone density in adult men. Life history theory predicts that environmental stress may prompt a reallocation of such investments to those functions critical to survival. We tested this hypothesis in two studies of rural Bolivian adult men by comparing free T levels and circadian rhythms during late winter, which is especially severe, to those in less arduous seasons. For each pair of salivary T_AM/T_PM samples (collected in a ～ 12‐h period), circadian rhythm was considered classic (C_CLASSIC) if T_AM > 110%T_PM, reverse (C_REVERSE) if T_PM > 110%T_AM, and flat (C_FLAT) otherwise. We tested the hypotheses that mean T_AM > mean T_PM and that mean T_LW < mean T_OTHER (LW = late winter, OTHER = other seasons). In Study A, of 115 T_PM–T_AM pairs, 51% = C_CLASSIC, 39% = C_REVERSE, 10% = C_FLAT; in Study B, of 184 T_AM–T_PM pairs, 55% = C_CLASSIC, 33% = C_REVERSE, 12% = C_FLAT. Based on fitting linear mixed models, in both studies T_OTHER‐AM > T_OTHER‐PM (A: P = 0.035, B: P = 0.0005) and T_OTHER‐AM > T_LW‐AM (A: P = 0.054, B: P = 0.007); T_PM did not vary seasonally, and T diurnality was not significant during late winter. T diurnality varied substantially between days within an individual, between individuals and between seasons, but neither T levels nor diurnality varied with age. These patterns may reflect the seasonally varying but unscheduled, life‐long, strenuous physical labor that typifies many non‐industrialized economies. These results also suggest that single morning samples may substantially underestimate peak circulating T for an individual and, most importantly, that exogenous signals may moderate diurnality and the trajectory of age‐related change in the male gonadal axis. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.