Adiposity attenuates muscle quality and the adaptive response to resistance exercise in non-obese, healthy adults.

BACKGROUND: Emerging data have revealed a negative association between adiposity and muscle quality (MQ). There is a lack of research to examine this interaction among young, healthy individuals, and to evaluate the contribution of adiposity to adaptation after resistance exercise (RE). OBJECTIVE: The purpose of this investigation was to examine the influence of subcutaneous adipose tissue (SAT) on muscle function among non-obese individuals before and after RE. DESIGN: Analyses included 634 non-obese (body mass index <30 kg m(-2)) subjects (253 males, 381 females; age=23.3 ± 5.2 years). SAT and muscle mass (magnetic resonance imaging-derived SAT and biceps muscle volume), isometric and dynamic biceps strength, and MQ (strength/muscle volume), were analyzed at baseline and after 12 weeks of unilateral RE. RESULTS: At baseline, SAT was independently associated with lower MQ for males (ß=-0.55; P<0.01) and females (ß=-0.45; P<0.01), controlling for body mass and age. Adaptation to RE revealed a significant negative association between SAT and changes for strength capacity (ß=-0.13; p=0.03) and MQ (ß=-0.14; P<0.01) among males. No attenuation was identified among females. Post-intervention SAT remained a negative predictor of MQ for males and females (ß=-0.47; P<0.01). CONCLUSIONS: The findings reveal that SAT is a negative predictor of MQ among non-obese, healthy adults, and that after 12 weeks of progressive RE this association was not ameliorated. Data suggest that SAT exerts a weak, negative influence on the adaptive response to strength and MQ among males.

Evaluation of agonist-antagonist properties of nitrogen mustard and cyano derivatives of delta 8-tetrahydrocannabinol.

delta 8-Tetrahydrocannabinol (delta 8-THC) is a naturally occurring cannabinoid with a characteristic pharmacological profile of in vivo effects. Previous studies have shown that modification of the structure of delta 8-THC by inclusion of a nitrogen-containing functional group alters this profile and may alkylate the cannabinoid receptor, similar to the manner in which beta-funaltrexamine (beta-FNA) alkylates the micro-opioid receptor. Two novel analogs of delta 8-THC were synthesized: a nitrogen mustard analog with a dimethylheptyl side chain (NM-delta 8-THC) and a cyano analog with a dimethylpentyl side chain (CY-delta 8-THC). Both analogs showed high affinity for brain cannabinoid receptors and when administered acutely, produced characteristic delta 9-THC-like effects in mice, including locomotor suppression, hypothermia, antinociception and catalepsy. CY-delta 8-THC shared discriminative stimulus effects with CP 55,940; for NM-delta 8-THC, these effects also occurred, but were delayed. Although both compounds attenuated the effects of delta 9-THC in the mouse behavioral tests, evaluation of potential antagonist effects of these compounds was complicated by the fact that two injections of delta 9-THC produced similar results, suggesting that acute tolerance or desensitization might account for the observations. NM-delta 8-THC, but not CY-delta 8-THC, attenuated the discriminative stimulus effects of CP 55,940 in rats several days following injection. Hence, addition of a nitrogen-containing functional group to a traditional cannabinoid structure does not eliminate agonist effects and may produce delayed attenuation of cannabinoid-induced pharmacological effects.

Synthesis and pharmacological evaluation of ether and related analogues of delta 8-, delta 9-, and delta 9,11-tetrahydrocannabinol.

The primary goal of this research was to synthesize a series of ether analogues of the cannabinoid drug class and to evaluate their agonist and antagonist pharmacological properties in either the mouse or the rat. Agonist and antagonist activity was evaluated in mice using a multiple-evaluation procedure (locomotor activity, tail-flick latency, hypothermia, ring immobility) and activity in rats determined in a discriminative stimulus paradigm. Additionally, novel analogues were evaluated for their ability to bind to the THC receptor site labeled by 3H-CP-55,940. None of the cannabinoid analogues were capable of attenuating the effects of delta 9-THC (3 mg/kg) in either the rat (doses up to 10 mg/kg) or in the mouse (doses up to 30 mg/kg). It also appears that the compounds with minimal in vivo activity are not mixed agonist/antagonists. These data would suggest that the phenolic hydroxyl is important for receptor recognition (binding) and in vivo potency. Additionally, cannabinoid methyl ethers previously considered inactive have been found to produce limited activity. Lastly, data suggest that delta 9,11-THC is more potent than previous reports indicated, and does possess pharmacological activity.

Sensitivity to sternotomy wires may cause postoperative pruritus.

An eczematous eruption developed on the anterior chest of a 58-year-old woman with known nickel sensitivity after the insertion of nickel-containing sternotomy wires. Her wound was revised with removal of the wires to give immediate and sustained relief from the itch. The electron microscopy and parasternal biopsy histology demonstrating a sarcoidal reaction are discussed.

The quantity and quality of physical activity among those trying to lose weight.

BACKGROUND: Regular exercise to elicit caloric expenditure is an important component for achieving weight loss. The Healthy People 2000 objectives recommend regular sustained physical activity lasting 30 minutes, five days per week (Objective 1.3) particularly for weight loss. Moreover, this recommendation has been restated for weight loss and overall health benefits in the Centers for Disease Control and Prevention / American College of Sports Medicine (CDC/ACSM) statement and Surgeon General's Report (SGR) on Physical ActivitY and Health. Thus, we sought to identify the relative quality, and quantity of physical activity among people trying to lose weight. DESIGN: Cross-sectional self-reported data from the West Virginia Behavioral Risk Factor Surveillance System (BRFSS) were used. The BRFSS is a state-based telephone survey of adults that uses a multistage cluster design based on the Waksberg method of random-digit dialing. Data froM 2769 men and 4490 women were obtained from the 1992, 1994, and 1996 surveys. RESULTS: Half (49.6%) of individuals trying to lose weight did not engage in any physical activity. Further, only 15% of respondents trying to lose weight reported exercising regularly. Nevertheless, those trying to lose weight were more likely (OR [odds ratio] = 1.3; 95% CI [confidence interval], 1.14, 1.51, p < 0.001) to exercise regularly than those not trying to lose weight. In particular, women trying to lose weight were significantly more likely (OR = 1.45; 95% CI, 1.22,1.74, p < 0.001) to exercise regularly than women not trying to lose weight. Conversely, men trying to lose weight were no more likely to exercise regularly (p = .23) than men not trying to lose weight. Among respondents who were using exercise for weight loss, only 14.7% were expending > or =1000 kcal/week and 18.2% were expending > or =500 kcal/week. Weekly expenditure rates of > or =1000 kcal/week were more likely to occur among men (17%) than women (13.8%), in younger age groups, and among those with higher educational attainment. CONCLUSION: These data suggest that while certain individuals trying to lose weight are more likely to engage in regular physical activity, most persons trying to lose weight have not adopted regular physical activity as part of their weight loss practice. These results suggest that public health efforts to effectively integrate physical activity into weight control practices of West Virginians have been minimally successful.

The acute effects of exercise intensity on HDL-C metabolism.

To determine whether exercise intensity influences acute HDL-C responses, 12 male recreational runners (24.8 +/- 4 yr) who ran 15-30 miles.wk-1 exercised on a motor driven treadmill at 60% (L) and 75% (H) VO2max. A counterbalanced experimental design was utilized and energy expenditure was 800 Kcal. Fasting blood samples were obtained 24 h before exercise (24 PRE), immediately post-(IPE), 1 h post- (1 h PE), 6 h post- (6 h PE), and 24 h post- (24 h PE) exercise and analyzed for HDL-C and HDL2&3-C. In addition, postheparin plasma samples, obtained 24 h PRE, 6 h PE, and 24 h PE were analyzed for lipolytic activity--LPLA and HTGLA. An exercise trial by time interaction was observed for HDL-C (P < 0.01). Post-hoc analysis revealed no change in HDL-C following the L trial. However, an increase in HDL-C was observed 24 h PE (P < 0.01) following the H trial. The increase in HDL-C was attributed to an elevated HDL3-C (P < 0.01), with no change in HDL2-C. Analysis of plasma lipolytic activity revealed an increase in LPLA 24 h PE (P < 0.05) which may be responsible for the postexercise alterations in HDL-C. However, HTGLA decreased 6 h PE (P < 0.01) and 24 h PE (P < 0.05). We conclude that increases in HDL-C levels following endurance activity are influenced, in part, by the exercise intensity.

Effect of different quantities of variable practice on acquisition, retention, and transfer of an applied motor skill.

This investigation examined the effect of manipulating different quantities of variable practice in the acquisition phase on the retention and transfer performance of a dart throw. Participants in the Specific condition practiced a total of 75 acquisition trials from a distance of 2.39 m. Participants in the Specific + Variable condition practiced a total of 75 acquisition trials with 25 trials from distances of 1.47 m, 2.39 m, and 3.30 m. Participants in the Specific + Varplus condition practiced a total of 75 acquisition trials with 15 trials from distances of 1.47 m, 1.93 m, 2.39 m, 2.84 m, and 3.30 m. Results of the one-way analysis of variance on the 24-hr. retention test from 2.39 m yielded no significant differences among practice conditions for mean radial error. A one-way analysis of variance on the 24-hr. transfer test from 3.76 m indicated that the Specific + Variable and Specific + Varplus conditions performed with significantly smaller mean radial error than the Specific condition. The results are discussed in regard to recent research and applicability to instructional settings.

Physical activity and osteoporosis: disparities between knowledge and practice.

Osteoporosis and osteoporosis-related conditions are national health priorities, and physical activity has been associated with a reduction of osteoporosis risk factors (i.e., increased bone mineral density and decreased falls). Our study examined the disparity between awareness of physical activity as an osteoporosis prevention strategy and the quantity and quality of physical activity performed. Results indicate that most individuals view physical activity as an important prevention strategy. However, few participants are engaged in physical activity which meets current public health recommendations despite their awareness of physical activity health benefits. Barriers to regular exercise are discussed as well as promising approaches to reducing barriers through alterations to physical and social environments.

Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy.

We sought to determine whether acute resistance exercise (RE)-induced gene expression is modified by RE training. We studied the expression patterns of a select group of genes following an acute bout of RE in naïve and hypertrophying muscle. Thirteen untrained subjects underwent supervised RE training for 12 wk of the nondominant arm and performed an acute bout of RE 1 wk after the last bout of the training program (training+acute). The dominant arm was either unexercised (control) or subjected to the same acute exercise bout as the trained arm (acute RE). Following training, men (14.8 ± 2.8%; P < 0.05) and women (12.6 ± 2.4%; P < 0.05) underwent muscle hypertrophy with increases in dynamic strength in the trained arm (48.2 ± 5.4% and 72.1 ± 9.1%, respectively; P < 0.01). RE training resulted in attenuated anabolic signaling as reflected by a reduction in rpS6 phosphorylation following acute RE. Changes in mRNA levels of genes involved in hypertrophic growth, protein degradation, angiogenesis, and metabolism commonly expressed in both men and women was determined 4 h following acute RE. We show that RE training can modify acute RE-induced gene expression in a divergent and gene-specific manner even in genes belonging to the same ontology. Changes in gene expression following acute RE are multidimensional, and may not necessarily reflect the actual adaptive response taking place during the training process. Thus RE training can selectively modify the acute response to RE, thereby challenging the use of gene expression as a marker of exercise-induced adaptations.

Chronic disease risk among adults with cerebral palsy: the role of premature sarcopoenia, obesity and sedentary behaviour.

Premature declines in function among adults with cerebral palsy (CP) are generally attributed to weakness, spasticity and orthopaedic abnormalities, as well as chronic pain and fatigue. Very little research or clinical attention has been devoted to the confluence and consequences of early muscle wasting and obesity as mediators of secondary comorbidity in this population, and perhaps more importantly, to the role of lifestyle to potentiate these outcomes. At present, there are no national surveillance programmes that monitor chronic health in adults with CP; however, mortality records have demonstrated a greater prevalence of coronary heart disease as compared with the general population. Although by definition, CP is a 'non-progressive' condition, secondary factors such as habitual sedentary behaviour, obesity, and premature sarcoepenia may increase the severity of functional impairment throughout adulthood, and lead to cardiometabolic disease, fragility and/or early mortality. Herein we describe the heightened health risk represented in adults with CP, and discuss the hallmark phenotypic features that coincide with ageing, obesity and cardiometabolic disorders. Moreover, we provide discussion regarding the protective role of habitual physical activity to stimulate anti-inflammatory pathways and to ameliorate global risk. Although physical therapeutic modalities are already widely acknowledged as a vital component to improve movement quality in CP, the purpose of this review was to present a compelling case for the value of lifelong physical activity participation for both function and cardiometabolic health preservation.

Leptin and leptin receptor genetic variants associate with habitual physical activity and the arm body composition response to resistance training.

PURPOSE: We investigated the influence of Leptin (LEP) and leptin receptor (LEPR) SNPs on habitual physical activity (PA) and body composition response to a unilateral, upper body resistance training (RT) program. METHODS: European-derived American volunteers (men=111, women=131, 23.4 ± 5.4 yr, 24.4 ± 4.6 kg·m(-2)) were genotyped for LEP 19 G>A (rs2167270), and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183). They completed the Paffenbarger PA Questionnaire. Arm muscle and subcutaneous fat volumes were measured before and after 12 wk of supervised RT with MRI. Multivariate and repeated measures ANCOVA tested differences among phenotypes by genotype and gender with age and body mass index as covariates. RESULTS: Adults with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA (1273.3 ± 176.8, p=0.017) and sports/recreation (1922.8 ± 226.0, p<0.04) than A allele carriers (718.0 ± 147.2, 1328.6 ± 188.2, respectively). Those with the LEP 19 GG genotype spent more h/wk in light intensity PA (39.7 ± 1.6) than A allele carriers (35.0 ± 1.4, p=0.03). In response to RT, adults with the LEPR 668 G allele gained greater arm muscle volume (67,687.05 ± 3186.7 vs. 52,321.87 ± 5125.05 mm(3), p=0.01) and subcutaneous fat volume (10,599.89 ± 3683.57 vs. -5224.73 ± 5923.98 mm(3), p=0.02) than adults with the LEPR 668 AA genotype, respectively. CONCLUSION: LEP19 G>A and LEPR 668 A>G associated with habitual PA and the body composition response to RT. These LEP and LEPR SNPs are located in coding exons likely influencing LEP and LEPR function. Further investigation is needed to confirm our findings and establish mechanisms for LEP and LEPR genotype and PA and body composition associations we observed.

Rapid access to genes of biotechnologically useful enzymes by partial genome sequencing: the thermoalkaliphile Anaerobranca gottschalkii.

Anaerobranca gottschalkii strain LBS3 T is an extremophile living at high temperature (up to 65 degrees C) and in alkaline environments (up to pH 10.5). An assembly of 696 DNA contigs representing about 96% of the 2.26-Mbp genome of A. gottschalkii has been generated with a low-sequence-coverage shotgun-sequencing strategy. The chosen sequencing strategy provided rapid and economical access to genes encoding key enzymes of the mono- and polysaccharide metabolism, without dilution of spare resources for extensive sequencing of genes lacking potential economical value. Five of these amylolytic enzymes of considerable commercial interest for biotechnological applications have been expressed and characterized in more detail after identification of their genes in the partial genome sequence: type I pullulanase, cyclodextrin glycosyltransferase (CGTase), two alpha-amylases (AmyA and AmyB), and an alpha-1,4-glucan-branching enzyme.

Hemiplegia--a rare complication of acute Epstein-Barr virus (EBV) infection.

A 32-year-old male presented to hospital with a transient hemiplegia associated with a rash and systemic upset. He was found to have an acute Epstein-Barr virus (EBV) infection. Hemiplegia complicating glandular fever has been described but once previously.

Metal ion coordination by the AGC triad in domain 5 contributes to group II intron catalysis.

Group II introns require numerous divalent metal ions for folding and catalysis. However, because little information about individual metal ions exists, elucidating their ligands, functional roles and relationships to each other remains challenging. Here we provide evidence that an essential motif at the catalytic center of the group II intron, the AGC triad within domain 5 (D5), provides a ligand for a crucial metal ion. Sulfur substitution of the pro-Sp oxygen of the adenosine strongly disrupts D5 binding to a substrate consisting of an exon and domains 1-3 of the intron (exD123). Cd2+ rescues this effect by enabling the sulfur-modified D5 to bind to exD123 with wild type affinity and catalyze 5'-splice site cleavage. This switch in metal specificity implies that a metal ion interacts with D5 to mediate packing interactions with D123. This new D5 metal ion rescues the disruption of D5 binding and catalysis with a thermodynamic signature different from that of the metal ion that stabilizes the leaving group during the first step of splicing, suggesting the existence of two distinct metal ions.

Kinetic characterization of the second step of group II intron splicing: role of metal ions and the cleavage site 2'-OH in catalysis.

The ai5gamma group II intron from yeast excises itself from precursor transcripts in the absence of proteins. When a shortened form of the intron containing all but the 3'-terminal six nucleotides is incubated with an exon 1 oligonucleotide and a 3' splice site oligonucleotide, a nucleotidyl transfer reaction occurs that mimics the second step of splicing. As this tripartite reaction provides a means to identify important functional groups in 3' splice site recognition and catalysis, we establish here a minimal kinetic framework and demonstrate that the chemical step is rate-limiting. We use this framework to characterize the metal ion specificity switch observed previously upon sulfur substitution of the 3'-oxygen leaving group and to elucidate by atomic mutagenesis the role of the neighboring 2'-OH in catalysis. The results suggest that both the 3'-oxygen leaving group and the neighboring 2'-OH are important ligands for metal ions in the transition state but not in the ground state and that the 2'-OH may play an additional role in transition state stabilization by donating a hydrogen bond. Metal specificity switch experiments combined with quantitative analysis show that the Mn(2+) that interacts with the leaving group binds to the ribozyme with the same affinity as the metal ion that interacts with the neighboring 2'-OH, raising the possibility that a single metal ion mediates interactions with the 2'- and 3'-oxygen atoms at the 3' splice site.

The regressing keratoacanthoma.

The clinical and pathological features of 11 cases of regressing keratoacanthoma are presented. These lesions were from sun-exposed skin of individuals between the ages of 58 and 92 years and were of short clinical duration (2-12 months). Histologically, these lesions showed similar features and consisted of symmetrical shallow cup-shaped invaginations of thin atrophic epidermis with overhanging edges. The underlying papillary dermis demonstrated variable degrees of inflammatory infiltrate and scarring. It is important to recognize these features as representing regressed keratoacanthoma as they may be confused with other unrelated skin conditions.

Pseudosepsis in rheumatoid arthritis due to cellular and lipid abnormalities in synovial fluid.

In acute septic arthritis, the synovial fluid is usually frankly purulent. However, the presence of pus does not always imply the presence of infection, and some synovial fluids are easily mistaken for pus. An exaggeration of the normal leucocyte response in inflammatory joint fluids may alone simulate sepsis; marked increases in certain lipid fractions of the fluid may produce similar appearances. We describe a patient who presented with two examples of such 'pseudoseptic arthritis'.