Effect of muscle glycogen content on exercise-induced changes in muscle T2 times

Effects of gastrocnemius glycogen (Gly)concentration on changes in transverse relaxation time (T2; ms) werestudied after 5-min plantar flexion at 25% of maximum voluntarycontraction (MVC). Gastrocnemius Gly, phosphorus metabolites, and T2were measured in seven subjects by using interleaved¹³C/³¹Pmagnetic resonance spectroscopy (MRS) at 4.7 T and magnetic resonanceimaging (MRI; 1.5 T). After baseline MRS/MRI, subjects exercised for 5 min at 25% of MVC and were reexamined (MRS/MRI). Subjects thenperformed ~15 min of single-leg toe raises (50 ± 2% of MVC),depleting gastrocnemius Gly by 43%. After a 1-h rest (for T2 return tobaseline), subjects repeated the 5-min protocol, followed by a finalMRI/MRS. After the initial 5-min protocol, T2 values increased by 5.9 ± 0.8 ms (29.9 ± 0.4 to 35.8 ± 0.6 ms), whereas Gly did notchange significantly (70.5 ± 6.8 to 67.6 ± 7.4 mM). After 15 min of toe raises, gastrocnemius Gly was reduced to 40.4 ± 5.3 mM(P  0.01), recovering to 45.8 ± 5.3 mM (P  0.05) during a 1-h rest.After the second 5-min bout of plantar flexion (reduced Gly at 25% ofMVC), T2 values increased by 5.0 ± 0.8 ms (30.4 to 35.4 ms),whereas muscle Gly rose to 57.6 ± 5.3 mM. We conclude that muscleGly concentration per se does not affect exercise-induced T2 increasesin the human gastrocnemius.

     

Feeding experiments on Penilia avirostris dana (cladocera: crustacea)

Feeding in the marine cladoceran, Penilia avirostris Dana, was investigated using plastic micronic beads as a controlled particle source. The range of bead size ingested by P. avirostris was largely limited to diameters of 20 μm and below, perhaps a competitive advantage in nature, was found that: (1) as the concentration of beads increased, the number of beads ingested increased: (2) as the number of P. avirostris increased, the number of beads ingested increased: and (3) the number of beads ingested also increased with body size. The size of P. avirostris, however, did not appear to limit the size of bead ingested, while larger sized animals may be better competitors for particles.     

Controlled Porosity Solubility Modulated Osmotic Pump Tablets of Gliclazide

A system that can deliver drug at a controlled rate is very important for the treatment of various chronic diseases such as diabetes, asthma, and heart disease. Poorly water-soluble drug with pH-dependent solubility such as gliclazide (GLZ) offers challenges in the controlled-release formulation because of low dissolution rate and poor bioavailability. Solid dispersion (SD) of GLZ consisted of hydroxypropyl cellulose (HPC-SSL) as a polymeric solubilizer was manufactured by hot melt extrusion (HME) technology. Then, controlled porosity osmotic pump (CPOP) tablet of gliclazide was designed to deliver drug in a controlled manner up to 16 h. The developed formulation was optimized for type and level of pore former and coating weight gain. The optimized formulation was found to exhibit zero order kinetics independent of pH and agitation speed but depends on osmotic pressure of dissolution media indicated that mechanism of drug release was osmotic pressure. The in vivo performance prediction of developed formulation using convolution approach revealed that the developed formulation was superior to the existing marketed extended-release formulation in terms of attaining steady state plasma levels and indicated adequate exposure in translating hypoglycemic response. The prototype solubilization method combined with controlled porosity osmotic pump based technique could provide a unique way to increase dissolution rate and bioavailability of many poorly water-soluble, narrow therapeutic index drugs used in diabetes, cardiovascular diseases, etc.KEY WORDS: convolution approach, gliclazide, hot melt extrusion (HME), hydroxypropyl cellulose, solid dispersion     

Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis

Introduction

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years.

Methods

In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years.

Results

68% of the patients had accelerated hand BMD loss (>-0.003 g/cm²) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage.

Conclusions

In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.     

Has Armstrong's cycle efficiency improved?

This case describes the physiological maturation from ages 21 to 28 yr of the bicyclist who has now become the six-time consecutive Grand Champion of the Tour de France, at ages 27-32 yr. Maximal oxygen uptake (Vo(2max)) in the trained state remained at approximately 6 l/min, lean body weight remained at approximately 70 kg, and maximal heart rate declined from 207 to 200 beats/min. Blood lactate threshold was typical of competitive cyclists in that it occurred at 76-85% Vo(2max), yet maximal blood lactate concentration was remarkably low in the trained state. It appears that an 8% improvement in muscular efficiency and thus power production when cycling at a given oxygen uptake (Vo(2)) is the characteristic that improved most as this athlete matured from ages 21 to 28 yr. It is noteworthy that at age 25 yr, this champion developed advanced cancer, requiring surgeries and chemotherapy. During the months leading up to each of his Tour de France victories, he reduced body weight and body fat by 4-7 kg (i.e., approximately 7%). Therefore, over the 7-yr period, an improvement in muscular efficiency and reduced body fat contributed equally to a remarkable 18% improvement in his steady-state power per kilogram body weight when cycling at a given Vo(2) (e.g., 5 l/min). It is hypothesized that the improved muscular efficiency probably reflects changes in muscle myosin type stimulated from years of training intensely for 3-6 h on most days.     

Bollworm (Lepidoptera: Noctuidae) survival on 'Bollgard' and 'Bollgard II' cotton flower bud and flower components.

Genetically modified cotton, Gossypium hirsutum L., cultivars ('Bollgard') that produce crystalline proteins from Bacillus thuringiensis (Berliner) are valuable tools for managing lepidopteran insect pests in the United States. However, high numbers of bollworm, Helicoverpa zea (Boddie), larvae have been observed feeding in white flowers of these cultivars. Fresh tissue bioassays were conducted to investigate bollworm survival on Bollgard and 'Bollgard II' cottons. Bollworm survival was higher on square and flower anthers than on other floral structures on 'Deltapine 5415' (conventional cotton) and 'NuCOTN 33B' (Bollgard). Bollworm survival at 72 h was higher on all floral structures from Deltapine 5415 than on corresponding structures from NuCOTN 33B. ELISA tests indicated that CryIA(c) expression varied among plant parts; however, bollworm survival did not correlate with protein expression levels. Trends in bollworm survival on Bollgard II were similar to those on Bollgard and conventional cotton; however, survival was lower on all structures of Bollgard II than on corresponding structures of Bollgard and conventional cotton. These data support field observations of bollworm injury to white flowers and small bolls and provide a better understanding of larval behavior on Bollgard cotton.     

Increased sensitivity of a direct fluorescent antibody test for Legionella pneumophila in bronchoalveolar lavage samples by immunomagnetic separation based on BioMags

In the present study, immunomagnetic separation of Legionella pneumophila from mock bronchoalveolar lavage (BAL) fluid samples, which were artificially spiked with L. pneumophila, and culture positive patient BAL fluid samples, was achieved using BioMags (superparamagnetic particles) loaded with purified rabbit immunoglobulin G specific for L. pneumophila. Bacteria binding onto BioMag-immunomatrix were directly stained with a L. pneumophila species-specific DFA reagent and examined under a fluorescence microscope. BioMag-based immunomagnetic separation (BIMS) followed by DFA staining (BIMS-DFA) could correctly identify all the 20 (100%) BAL samples which were spiked with low numbers (2x10(2) CFU) of L. pneumophila. Cultures could be recovered from 15 (75%) of these 20 spiked BAL samples, 5 (25%) of the samples failed to yield positive cultures. Both culture and BIMS-DFA methods showed 100% positive results when spiked BAL samples containing high bacterial load (10(4) CFU) were tested. The findings with true patient culture positive BAL specimens which were examined retrospectively indicated that BIMS-DFA is significantly more sensitive for detecting L. pneumophila than conventional cytospin method of DFA staining (cytospin-DFA). Out of the 25 culture positive BAL specimens tested, 7 (28%) proved negative by cytospin-DFA whereas BIMS-DFA correctly detected all the 25 (100%) specimens. It is suggested that the BIMS-DFA procedure increases the sensitivity of DFA testing for L. pneumophila in large volume samples such as BAL fluids.     

Hyperphagia-mediated obesity in transgenic mice misexpressing the RNA-editing enzyme ADAR2

ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine. To examine the physiologic consequences resulting from ADAR2 misexpression, we have generated mutant mice expressing either wild-type or deaminase-deficient ADAR2 transgenes under the control of the human cytomegalovirus promoter. Transgenic mice expressing either wild-type or inactive ADAR2 isoforms demonstrated adult onset obesity characterized by hyperglycemia, hyperleptinemia, and increased adiposity. Paired feeding analysis revealed that mutant mice on caloric restriction had a growth rate and body composition indistinguishable from wild-type littermates, indicating that the observed obesity predominantly results from hyperphagia rather than a metabolic derangement. The observation that expression of catalytically inactive ADAR2 also is capable of producing an obese phenotype in mutant animals suggests that ADAR2 may possess additional biological activities beyond those required for the site-selective deamination of adenosine or may interfere with the actions of other double-stranded RNA-specific binding proteins in the cell.     

Using stable isotope analysis to examine fall armyworm (Lepidoptera: Noctuidae) host strains in a cotton habitat

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), or fall armyworm, is an important agricultural pest of several crops in the Western Hemisphere, including cotton (Gossypium L.). Two morphologically identical host strains of fall armyworm exist that differ in plant host use and habitat distribution. The corn-strain is a primary pest of corn, Zea mays L., whereas the rice-strain is the majority population infesting rice (Oryza spp.) and turfgrass (Cynodon spp.). With the increased use of Bacillus thuringiensis (Bt) toxin-expressing cotton varieties and the necessity of ensuring adequate refuge areas to prevent the spread of Bt toxin resistance, it is crucial to identify the alternative plant hosts available for the fall armyworm population infesting cotton. Stable isotope analysis combined with the molecular analysis of strain-specific markers was used to investigate whether one or both strains routinely develop on cotton grown in the Mississippi delta. We found that the majority of fall armyworm adults present during the early cotton growing season arose from C4 plants (e.g., corn and sorghum, Sorghum vulgare Pers.) and that the only strain likely to be developing on cotton (a C3 plant) in substantial numbers was the corn-strain. The population distribution patterns observed were consistent with corn providing an important refuge for the fall armyworm strain infesting cotton and suggested that late season populations in the Mississippi delta may be migrants from more northern corn areas.