Effects of strength training on muscle power and serum hormones in middle-aged and older men.

Effects of 16-wk strength training on maximal strength and power performance of the arm and leg muscles and serum concentrations [testosterone (T), free testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 +/- 2 yr) and 11 older men (M64; 64 +/- 2 yr). During the 16-wk training, the relative increases in maximal strength and muscle power output of the arm and leg muscles were significant in both groups (P < 0.05-0.001), with no significant differences between the two groups. The absolute increases were higher (P < 0.01-0.05) in M46 than in M64 mainly during the last 8 wk of training. No significant changes were observed for serum T and FT concentrations. Analysis of covariance showed that, during the 16-wk training period, serum FT concentrations tended to decrease in M64 and increase in M46 (P < 0.05). However, significant correlations between the mean level of individual serum T and FT concentrations and the individual changes in maximal strength were observed in a combined group during the 16-wk training (r = 0.49 and 0.5, respectively; P < 0.05). These data indicate that a prolonged total strength-training program would lead to large gains in maximal strength and power load characteristics of the upper and lower extremity muscles, but the pattern of maximal and power development seemed to differ between the upper and lower extremities in both groups, possibly limited in magnitude because of neuromuscular and/or age-related endocrine impairments.     

Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition

An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetically altered strain of mice with reduced expression of this transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65% decrease in VAChT protein expression, respectively. VAChT deficiency alters synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear normal in that respect and could be used for analysis of central cholinergic function. Behavioral analyses revealed that aversive learning and memory are not altered in mutant mice; however, performance in cognitive tasks involving object and social recognition is severely impaired. These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system.     

Occurrence of skeletal deformities and osteological development in red porgy Pagrus pagrus larvae cultured under different rearing techniques

The present study describes the osteological development and the occurrence of skeletal deformities in red porgy Pagrus pagrus larvae in relation to the intensification of the rearing system. Eggs obtained from natural spawning were cultured under two different rearing systems: intensive (100 eggs l^?1) in 2000 l and semi‐intensive (mesocosm) system (5 eggs l^?1) in 40 000 l conico‐cylindrical tanks. Fish samples were periodically collected along the development from hatching to juveniles at 95 days post hatching (dph). Osteological development, meristic counts and the presence of skeletal deformities were evaluated. Despite the external appearance of the juveniles being similar to wild standards, X‐ray studies revealed a high number of fish (semi‐intensive: 37·8%; intensive: 45·5%) with skeletal deformities. Regardless of the rearing system, no significant interaction was found between the per cent of the most common deformities, axial deviations (lordosis and presence of fused vertebrae). Cranial deformities and kyphosis incidences, however, were significantly higher in intensively cultured P. pagrus. Also, the fused vertebrae in these fish were located mainly in the caudal area instead of pre‐haemal area for semi‐intensively reared P. pagrus. Moreover, a significant interaction was found between the total number of vertebrae and the type of rearing system used; fish from the intensive system showing a higher number of fish with an extra vertebrae (10 abdominal + 15 caudal). Present results suggest a relationship among feeding sequence, osteological development and deformity incidence and location in P. pagrus larvae.     

Low and moderate plyometric training frequency produces greater jumping and sprinting gains compared with high frequency

The purpose of this study was to examine the effect of 3 different plyometric training frequencies (e.g., 1 day per week, 2 days per week, 4 days per week) associated with 3 different plyometric training volumes on maximal strength, vertical jump performance, and sprinting ability. Forty-two students were randomly assigned to 1 of 4 groups: control (n = 10, 7 sessions of drop jump (DJ) training, 1 day per week, 420 DJs), 14 sessions of DJ training (n = 12, 2 days per week, 840 DJs), and 28 sessions of DJ training (n = 9, 4 days per week, 1680 DJs). The training protocols included DJ from 3 different heights 20, 40, and 60 cm. Maximal strength (1 repetition maximum [1RM] and maximal isometric strength), vertical height in countermovement jumps and DJs, and 20-m sprint time tests were carried out before and after 7 weeks of plyometric training. No significant differences were observed among the groups in pre-training in any of the variables tested. No significant changes were observed in the control group in any of the variables tested at any point. Short-term plyometric training using moderate training frequency and volume of jumps (2 days per week, 840 jumps) produces similar enhancements in jumping performance, but greater training efficiency (approximately 12% and 0.014% per jump) compared with high jumping (4 days per week, 1680 jumps) training frequency (approximately 18% and 0.011% per jump). In addition, similar enhancements in 20-m-sprint time, jumping contact times and maximal strength were observed in both a moderate and low number of training sessions per week compared with high training frequencies, despite the fact that the average number of jumps accomplished in 7S (420 jumps) and 14S (840 jumps) was 25 and 50% of that performed in 28S (1680 jumps). These observations may have considerable practical relevance for the optimal design of plyometric training programs for athletes, given that a moderate volume is more efficient than a higher plyometric training volume.     

The human anti-IL-1β monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis

Introduction

IL-1β is a proinflammatory cytokine driving joint inflammation as well as systemic signs of inflammation, such as fever and acute phase protein production.

Methods

ACZ885, a fully human monoclonal antibody that neutralizes the bioactivity of human IL-1β, was generated to study the potent and long-lasting neutralization of IL-1β in mechanistic animal models as well as in a proof-of-concept study in patients with rheumatoid arthritis (RA).

Results

The mouse IL-1 receptor cross-reacts with human IL-1β, and it was demonstrated that ACZ885 can completely suppress IL-1β-mediated joint inflammation and cartilage destruction in mice. This observation prompted us to study the safety, tolerability and pharmacodynamic activity of ACZ885 in RA patients in a small proof-of-concept study – the first to be conducted in humans. Patients with active RA despite treatment with stable doses of methotrexate were enrolled in this dose escalation study. The first 32 patients were split into four cohorts of eight patients each (six were randomly assigned to active treatment and two to placebo). ACZ885 doses were 0.3, 1, 3 and 10 mg/kg, administered intravenously on days 1 and 15. To explore efficacy within 6 weeks of treatment, an additional 21 patients were randomly assigned to the 10 mg/kg cohort, resulting in a total of 20 patients dosed with 10 mg/kg and 15 patients treated with placebo. There was clinical improvement (American College of Rheumatology 20% improvement criteria) at week 6 in the 10 mg/kg treatment group; however, this did not reach statistical significance (P = 0.085). A statistically significant reduction in disease activity score was observed after 4 weeks in the 10 mg/kg group. Onset of action was rapid, because most responders exhibited improvement in their symptoms within the first 3 weeks. C-reactive protein levels decreased in patients treated with ACZ885 within 1 week. ACZ885 was well tolerated. Three patients receiving ACZ885 developed infectious episodes that required treatment. No anti-ACZ885 antibodies were detected during the study.

Conclusion

ACZ885 administration to methotrexate-refractory patients resulted in clinical improvement in a subset of patients. Additional studies to characterize efficacy in RA and to determine the optimal dose regimen appear warranted.

Trial Registration

ClinicalTrials.gov identifier NCT00619905.     

Blocked negative selection of developing T cells in mice expressing the baculovirus p35 caspase inhibitor.

Clonal deletion in the thymus by apoptosis is involved in purging the immune system of self-reactive T lymphocytes (negative selection). Cysteine proteases (caspases) belonging to the CPP32 family are activated during this process. We have produced transgenic mice expressing baculovirus p35, a broad-range caspase inhibitor. Thymocytes from p35 transgenic mice were resistant in vitro to several apoptosis-inducing agents; this resistance correlated with the inhibition of CPP32-like activity. Negative selection in vivo of thymocytes triggered by two exogenous antigens, staphylococcal enterotoxin B superantigen and an antigenic peptide in the F5 T-cell receptor transgenic model, was specifically inhibited in p35 transgenic mice. Our results provide direct evidence for caspase involvement in negative selection during thymocyte development.     

Vitrification of calf oocytes: effects of maturation stage and prematuration treatment on the nuclear and cytoskeletal components of oocytes and their subsequent development

This study was designed to establish the effects of the meiotic stage of bovine oocytes and of a prematuration treatment with roscovitine (ROS) on their resistance to cryopreservation. Oocytes from prepubertal calves at the stages of germinal vesicle breakdown (GVBD) or at metaphase II (MII) were vitrified by the open pulled straw (OPS) method. In another experiment, oocytes were kept under meiotic arrest with 50 microM ROS for 24 hr and vitrified at the GVBD stage. After warming, some oocyte samples were fixed, stained using specific fluorescent probes and examined under a confocal microscope. The remaining oocytes were fertilized, and cleavage and blastocyst rates recorded. Significantly lower cleavage rates were obtained for the vitrified GVBD and MII oocytes (9.9% and 12.6%, respectively) compared to control oocytes (73.9%). Significantly worse results in terms of cleavage rates were obtained when GVBD calf oocytes were exposed to cryoprotectants (CPAs: ethylene glycol plus dimethyl sulfoxide, DMSO) (13.1%) or vitrified (1.6%) after a prematuration treatment with ROS, when compared to untreated control oocytes (68.7%) or ROS-control oocytes (56.6%). None of the vitrification procedures yielded blastocysts, irrespective of the initial meiotic stage or previous prematuration treatment. Compared to the control oocytes, significantly fewer oocytes exhibited normal spindle configuration after being exposed to CPAs or after vitrification of either GVBD or MII calf oocytes. These results indicate that the vitrification protocol has a deleterious effect on the meiotic spindle organization of calf oocytes cryopreserved at both the GVBD and MII stage, which impairs the capacity for further development of the embryos derived from these vitrified oocytes. Prematuration treatment with ROS has no beneficial effect on the outcome of vitrification by the OPS method.     

The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo

Background

The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV).

Methods

Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c⁺ CD8⁺ and CD11c^- CD8⁺ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8⁺ T cells was assessed by quantitative PCR.

Results

Following RSV infection CD11c⁺ CD8⁺ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8⁺ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8⁺ T cells in the absence of RSV infection, its mRNA was expressed in CD8⁺ T cells of both naïve and RSV infected mice. CD11c⁺, but not CD11c^-, CD8⁺ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c⁺ CD8⁺ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo.

Conclusion

CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo.