The effect of a 3-month moderate-intensity physical activity program on body composition in overweight and obese African American college females.

SUMMARY: This study evaluated body composition outcomes following a 3-month exercise program for overweight/obese Black women. BMI decreased over the 3-month study despite an observed increase in body fat. Enhancements in bone marrow density and muscle density were also observed. Results show promising yet hypothesis-generating findings to explore in future research. INTRODUCTION: Few studies have evaluated the relationship between aerobic physical activity (PA) and body composition among young adult overweight/obese African American (AA) women. PURPOSE: The current study evaluated the effect of a 3-month moderate-intensity aerobic physical activity intervention for overweight and obese young adult women on bone, lean, and fat mass. METHODS: Participants (n = 15) were a randomly selected subset of AA female college students (M age = 21.7 years; M BMI = 33.3) enrolled in a larger PA promotion pilot study (n = 31). Study protocol required participants to engage in four 30-60-min moderate-intensity aerobic PA sessions each week. Whole body composition was measured by dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) was used to assess additional quantitative and qualitative assessment of the radius. RESULTS: BMI decreased over the duration of the study (P = .034), reflected by a marginal decrease in body weight (P = .057). However, unexpectedly, increases in adipose tissue measures were observed, including total body fat (P = .041), percent body fat (P = .044), trunk fat (P = .031), and percent trunk fat (P = .041). No changes in DXA-measured bone outcomes were observed (i.e., bone mineral density, P = .069; bone mineral content, P = .211). Results from the pQCT assessment showed that bone marrow density increased (P = .011), but cortical density remained stable (P = .211). A marginally significant increase in muscle density (P = .053) and no changes in muscle area (P = .776) were observed. CONCLUSIONS: A 3-month moderate-intensity PA program was associated with several promising findings, including increased bone marrow and stabilization of body weight. However, the increase in adipose tissue and trend for decreased bone mineral density were unexpected and indicate the need for future studies with larger samples to further explore these outcomes.

A genotype risk score predicts type 2 diabetes from young adulthood: the CARDIA study.

AIMS/HYPOTHESIS: Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adulthood. We used Cox regression to build nested prediction models for incident type 2 diabetes based on clinical risk factors assessed in young adulthood (age, sex, race, parental history of diabetes, BMI, mean arterial pressure, fasting glucose, HDL-cholesterol and triacylglyercol), without and with a 38-variant genotype score. Models were compared with C statistics and continuous net reclassification improvement indices (NRI). RESULTS: Of 2,439 participants, 830 (34%) were black and 249 (10%) had a BMI ≥ 30 kg/m(2) at baseline. Over a mean 23.9 years of follow-up, 215 (8.8%) participants developed type 2 diabetes. The genotype score significantly predicted incident diabetes in all models, with an HR of 1.08 per risk allele (95% CI 1.04, 1.13) in the full model. The addition of the score to the full model modestly improved reclassification (continuous NRI 0.285; 95% CI 0.126, 0.433) but not discrimination (C statistics 0.824 and 0.829 in full models with and without score). Race-stratified analyses were similar. CONCLUSIONS/INTERPRETATION: Knowledge of genotype predicts type 2 diabetes over 25 years in white and black young adults but may not improve prediction over routine clinical measurements.

Mandibular phenotype of p20C/EBPbeta transgenic mice: Reduced alveolar bone mass and site-specific dentin dysplasia.

CCAAT enhancer binding proteins (C/EBP) comprise a family of basic-leucine zipper transcription factors that regulate cellular differentiation and function. To determine the role of C/EBP transcription factors in osteoblasts and odontoblasts, we generated a transgenic (TG) mouse model with Co1a1 (pOBCol3.6) promoter-targeted expression of a FLAG-tagged dominant negative C/EBP isoform, p20C/EBPbeta (previously LIP). Two of the four transgenic lines presented with abnormalities in the developing incisors, including breakage, overgrowth, and malocclusion. Histological examination revealed that the amount of alveolar bone was reduced in TG compared to wild-type (WT) mice. By microcomputed tomography (microCT), the bone volume fraction of the mandible was reduced at the level of the first and third molars, demonstrating a severe mandibular osteopenia. The lingual dentin morphology of TG incisors differed dramatically from WT. Labial dentin (enamel side) showed normal thickness and tubular dentin structure, whereas the lingual dentin was thinner (25-30% of WT at the alveolar crest) with an amorphous globular structure characteristic of dentin dysplasia. FLAG immunostaining was seen in both lingual and labial odontoblasts, indicating that the site-specific defect was not due to a lack of labial transgene expression. Northern blot analysis demonstrated reduced osteocalcin expression in TG mandibles, while bone sialoprotein was increased, consistent with prior results in calvariae and long bones. Dental sialophosphoprotein, a marker of the odontoblast lineage whose absence causes dentin dysplasia, was modestly reduced in TG mice by Northern blot and in situ hybridization analysis. By fluorescence microscopy, pOBCol2.3-GFP, a marker of the odontoblast lineage, was expressed in both labial and lingual odontoblasts, although GFP-marked lingual odontoblasts were more flattened than WT cells. Moreover, GFP-positive processes in the lingual dentin tubules were truncated and less organized than those in WT dentin. MicroCT analysis showed reduced tissue density in the lingual dentin. These data suggest that C/EBP transcription factors may be involved in the regulation of odontoblast polarization and dentin matrix production.

Degradation of xenobiotic compounds in situ: capabilities and limits.

Exploiting microorganisms for remediation of waste sites is a promising alternative to groundwater pumping and above ground treatment. The objective of in situ bioremediation is to stimulate the growth of indigenous or introduced microorganisms in regions of subsurface contamination, and thus to provide direct contact between microorganisms and the dissolved and sorbed contaminants for biotransformation. Subsurface microorganisms detected at a former manufactured gas plant site contaminated with coal tars mineralized significant amounts of naphthalene (8-43%) and phenanthrene (3-31%) in sediment-water microcosms incubated for 4 weeks under aerobic conditions. Evidence was obtained for naphthalene mineralization (8-13%) in the absence of oxygen in field samples. These data suggest that biodegradation of these compounds is occurring at the site, and the prospects are good for enhancing this biodegradation. Additional batch studies demonstrated that sorption of naphthalene onto aquifer materials reduced the extent and rate of biodegradation, indicating that desorption rate was controlling the biodegradation performance.

The action of polymyxin B at the frog neuromuscular junction.

1 The effects of polymyxin B at the neuromuscular junction of the frog were studied by conventional electrophysiological and voltage clamp techniques. 2 At a concentration of 2.5 micrograms/ml polymyxin B produced neuromuscular blockade in 10 to 15 min neuromuscular block was characterized by a depressed e.p.p. quantal content (28 plus or minus 7), which was similar to that determined from endplates exposed to 13 mM magnesium (23 plus or minus 3), and a low e.p.p. quantal size, which was similar to that determined from endplates exposed to 3 microM (+)-tubocurarine. 3 Polymyxin B (0.25 to 0.75 micrograms/ml) decreased mean miniature e.p.pl amplitude with little effect on frequency. At a concentration of 5 micrograms/ml polymyxin B markedly shortened the duration of endplate currents (e.p.cs) and abolished the relationship between holding potential and the time to half-decay at negative potentials greater than -60 mV. This action is consistent with block of open acetylcholine activated ionic channels. 5 4-Aminopyridine (20 micrometers) antagonized the depressed e.p.p. quantal content produced by polymyxin B but did not alter the shortened e.p.c. duration. 6 It is concluded that polymyxin B decreases quantal release and produces some degree of postjunctional receptor blockade and a marked and persistent blockade of of acetylcholine activated channels. The latter action may explain the difficulty of reversal of polymyxin B-induced neuromuscular blockade and its non-competitive nature.

Biotreatment of PAH-contaminated soils/sediments.

The importance of chemical conditions and mass transfer effects to in situ bioremediation of PAHs is presented using a case study. In situ bioremediation is being evaluated as a means for remediating a coal-tar contaminated aquifer at the site of a former manufactured gas plant. Two objectives of this work have been to evaluate the potential for the indigenous bacteria to biodegrade coal tar constituents and to identify factors controlling biodegradation rates. Aquifer sediments collected from a variety of locations across the site contain bacteria capable of aerobically mineralizing some of the principal aromatic compounds in the groundwater plume (benzene, naphthalene, and phenanthrene). Parallel mineralization assays incubated under aerobic and anaerobic conditions strongly suggest that O2 availability is a primary factor controlling the rate and extent of biodegradation. Data indicate that sorption may have also significantly affected biodegradation rates by limiting the bioavailability of the aromatic compounds. A mass transfer-limited numerical model was developed to explore the effect of sorption and bioavailability on biodegradation rates. In this model biodegradation rates are proportional to aqueous concentration, which is directly reduced by sorption. Both biotransformation and bacterial growth are described as being controlled by the rate of desorptive mass transfer. The influence of sorption on biodegradation is quantified by defining a Bioavailability Factor, Bf. A Thiele Modulus which indicates the ratio of characteristic times for sorption and biodegradation is helpful for determining the extent of mass transfer control during biodegradation of the aromatic compounds. This approach is preferred to equilibrium partitioning models, which may overestimate biodegradation rates by failing to consider the effect of rate-limited desorption on bioavailability.

The effects of 3,4-diaminopyridine on acetylcholine release at the frog neuromuscular junction.

The effects of 3,4-diaminopyridine (3,4-DAP) were studied on spontaneous and evoked transmitter release in the frog sartorius muscle preparation. At a concentration of 1 mM, 3,4-DAP caused the appearance of spontaneous giant potentials, this effect of 3,4-DAP also occurred in absence of extracellular calcium. At lower concentrations in magnesium Ringer 3,4-DAP (1-10 microM) increased e.p.p. quantal content without causing the appearance of spontaneous giant potentials, 3,4-DAP prolonged muscle action potential (1 mM) and it is suggested that prolongation of the nerve terminal action potential by 3,4-DAP contributes largely to the increased evoked acetylcholine release. The ability of 3,4-DAP to cause the appearance of giant spontaneous potentials is considered to be independent of the drug's known ability to inhibit potassium conductance in excitable membranes, and may be due to the release of performed multiquantal packets of acetylcholine as suggested for vinblastine. It is concluded that 3,4-DAP is a useful tool in the study of both evoked and spontaneous acetylcholine release.

The action of dantrolene on transmitter mobilization at the rat neuromuscular junction.

Dantrolene sodium (20 microM) was found to decrease transmitter mobilization and the apparent available store of acetylcholine at frequencies of nerve stimulation of 50 and 100 Hz at the neuromuscular junction of the rat hemidiaphragm preparation treated with 2 microM (+)-tubocurarine. This effect of dantrolene sodium was not as marked at frequencies of nerve stimulation of 25 Hz or less, also no significant effect of the drug was observed on the amplitude of endplate potentials (EPPS) at any frequency of nerve stimulation. No effect of dantrolene sodium (20 microM) on mean miniature EPP amplitude or frequency was observed. It is suggested that the action of dantrolene sodium on mean EPP quantal content may be due to an action on stores of bound calcium within the motor nerve terminal. This effect of the drug is unlikely to be of physiological consequence in vivo, since it was only observed at high frequencies of nerve stimulation and did not cause a significant reduction of EPP amplitude during trains of stimuli.

Inhibition of aminopyridine-induced contractile activity in skeletal muscle by tetrodotoxin and by magnesium.

The effects of tetrodotoxin and magnesium have been studied on aminopyridine-induced contractile activity seen in the absence of nerve stimulation. In the chick biventer cervicis muscle both tetrodotoxin and magnesium pretreatment prevented the development of fasciculations and contractures in the presence of 4-aminopyridine and 3,4-diaminopyridine. Both tetrodotoxin and magnesium abolished aminopyridine induced fasciculations and contractures. Tetrodotoxin did not reduce postjunctional sensitivity to the agonists acetylcholine and carbachol whereas magnesium produced some reduction of postjunctional sensitivity. It is concluded that conducted action potentials must be involved in the aminopyridine-induced contractile activity. In the frog sartorius muscle aminopyridines occasionally induced repetitive endplate potentials suggesting that the compounds induce repetitive nerve activity. In both tetrodotoxin and magnesium treated preparations 4-aminopyridine produced only a moderate increase in miniature endplate potential frequency. It is concluded that aminopyridines increase nerve membrane excitability resulting in the generation of repetitive action potentials in the absence of nerve stimulation.

A comparison of 3,4-diaminopyridine and 4-aminopyridine in the anaesthetized cat.

3,4-Diaminopyridine and 4-aminopyridine were compared in the anaesthetized cat and found to be equiactive in their anti-curare activity. This in vivo similarity is at variance with previous in vitro studies which demonstrate 3,4-diaminopyridine to be more active than 4-aminopyridine at the neuromuscular junction. Possible reasons for the similarity between the two aminopyridines at the in vivo neuromuscular junction are discussed and it is concluded that 3,4-diaminopyridine has only marginal advantages over 4-aminopyridine as a potential anti-curare agent.

The neuromuscular and autonomic blocking activities of pancuronium, Org NC 45, and other pancuronium analogues, in the cat.

Twenty-six mono- or bis-quaternary salts of 3,17-dioxy-2 beta, 16 beta-dipiperidino-5 alpha-androstanes (including pancuronium) and one 17-desoxy congener were tested for neuromuscular blocking and autonomic blocking activities in the chloralose-anaesthetized cat. The 17 beta-acetoxy series, all the members of which contain an acetylcholine-like fragment in the steroidal D-ring, was most selective for effecting neuromuscular blockade. The salient member of this series is 3 alpha, 17 beta-diacetoxy-2 beta, 16 beta-dipiperidino-5 alpha-androstane 16 beta-N-monomethobromide (Org NC 45) which is highly selective in blocking neuromuscular transmission in that a dose approximately sixty times greater than the neuromuscular blocking dose was required to block responses to vagal stimulation. In contrast, in doses sufficient to produce neuromuscular block, pancuronium simultaneously blocked responses to vagal stimulation. Moreover, pancuronium and Org NC 45 exhibited the same order of neuromuscular blocking activity and therefore the latter potentially represents a useful addition to the armamentarium of neuromuscular blocking agents currently in clinical use.

Is there a clinical interaction between low molecular weight heparin and non-steroidal analgesics after total hip replacement?

The benefits of parenteral non-steroidal analgesic drugs and low molecular weight heparin anticoagulants have been shown before, but there is concern that the use of these agents in combination may potentiate haemorrhagic side-effects because of simultaneous inhibition of the clotting cascade and platelet mechanisms of haemostasis. In a prospective controlled trial, 60 patients undergoing total hip replacement were randomised into two groups. Those in one group received intramuscular ketorolac and those in the other group opioid analgesia. All patients received enoxaparin subcutaneously, once daily. There were 34 patients in the NSAID group and 26 in the opiate group. There were no significant differences between the two groups for intraoperative blood loss, postoperative drainage, transfusion requirements, bruising, wound oozing and leg swelling. From this study it would appear that there is a low risk of significant haemostatic potentiation associated with concurrent use of low molecular weight heparin and a modest dose of ketorolac tromethamine.

Empirical evidence does not support an association between less ambitious pre-treatment goals and better treatment outcomes: a meta-analysis.

Setting realistic weight loss goals may play a role in weight loss. We abstracted data from randomized controlled trials and observational studies conducted between 1998 and 2012 concerning the association of weight loss goals with weight loss. Studies included those that (i) were conducted in humans; (ii) delivered a weight loss intervention; (iii) lasted ≥6 weeks; (iv) assessed baseline weight loss goals; (vi) assessed pre- and post-weight either in the form of body mass index or some other measure that could be converted to weight loss based on information included in the original study or later provided by the author(s); and (vii) assessed the correlation between weight loss goals and final weight loss or provided data to calculate the correlation. Studies that included interventions to modify weight loss goals were excluded. Eleven studies met inclusion criteria. The overall correlation between goal weight and weight at intervention completion was small and statistically insignificant (ρ=0.0 5 ; P = 0.20). The current evidence does not demonstrate that setting realistic goals leads to more favourable weight loss outcomes. Thus, our field may wish to reconsider the value of setting realistic goals in successful weight loss.

Establishment of a new human pneumococcal standard reference serum, 007sp.

Lot 89SF has been the reference standard serum pool used in pneumococcal enzyme-linked immunosorbent assays (ELISAs) since 1990. In 2005, it was estimated that there remained between 2 and 5 years' supply of lot 89SF. Since lot 89SF was the reference standard used in the evaluation of the seven-valent pneumococcal conjugate vaccine Prevnar (PCV7), the link to clinical efficacy would be severed if stocks became completely depleted. Furthermore, demonstration of immune responses comparable to those elicited by PCV7 is a licensure approach used for new pneumococcal conjugate vaccines, so a replacement reference standard was required. A total of 278 volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice within 120 days following immunization. Plasma was prepared, pooled, and confirmed to be free from hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. The pooled serum was poured at 6 ml per vial into 15,333 vials and lyophilized. Immunological bridging of 007sp to 89SF was used to establish equivalent reference values for 13 pneumococcal capsular serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) by five independent laboratories. Antibody concentrations in 007sp were established relative to the lot 89SF reference preparation using the WHO reference ELISA. Subsequently, 12 existing WHO calibration sera had concentrations reassigned for 13 pneumococcal serotypes using new serum 007sp as the reference, and these were compared to concentrations relative to the original reference serum. Agreement was excellent for the 12 WHO calibration sera. The 007sp preparation has replaced 89SF as the pneumococcal reference standard. Sufficient quantity of this new preparation is available such that, with judicious use, it should be available for at least 25 years.

Org. 6368: a nondepolarizing neuromuscular blocking agent with a novel effect on end-plate conductance.

The effects of the nondepolarizing agent pancuronium and three derivatives on end-plate currents (e.p.c.s), evoked by neural stimulation at the amphibian neuromuscular junction, were investigated using conventional voltage clamp techniques. All four agents depressed peak e.p.c. amplitude and also shortened the exponential time constant of the e.p.c. decay compared with control. The properties of one derivative, Org. 6368, were investigated in detail and revealed the drug to produce marked blockade of end-plate ionic conductance relative to receptor blockade. Analysis of the kinetic behavior of Org. 6368 revealed a novel mechanism of channel blockade and dissociation which is very different to that observed with some of the local anesthetics. The rate of association of Org. 6368 with the channel binding site, 1.92 X 10(7) M-1 sec-1 at 0 mV, had virtually no dependence on membrane voltage with an e-fold increase with a change of voltage of 2940 mV while the rate of dissociation, 26.4 sec-1 at 0 mV, exhibited a marked dependence on voltage with an e-fold increase with a change of voltage of only -39.5 mV. It is proposed that the rate of association of Org. 6368 is rate limited by diffusion while the rate of dissociation from the channel binding site is increased by hyperpolarization, due to the drug molecule being attracted into the membrane field before leaving the binding site.

Cumulation of neomycin and its residual potentiation of tubocurarine in the cat.

Cumulation and interaction of neuromuscular blocking effects of neomycin and tubocurarine were determined on responses of the tibialis anterior muscle of the anaesthetized cat to indirect stimulation. Neuromuscular block produced by neomycin was cumulative despite rapid and apparent full recovery of twitch tension and an interval of 3 h between dose-response studies. Ed50 of neomycin on twitch tension decreased (P less than 0.05) from 22 +/- 4 mg kg-1 to 12 +/- 3 mg kg-1 after 3 h; marked post-tetanic exhaustion was observed after the antibiotic. Neuromuscular block (80-90%) with neomycin 25-30 mg kg-1 followed by full recovery and 3-h interval decreased (P less than 0.05) the ED50 of tubocurarine on twitch tension from 0.2 +/- 0.02 mg kg-1 to 0.13 +/- 0.03 mg kg-1. Tubocurarine exhibited no cumulative effects at intervals of 2 h and did not significantly affect the response of twitch and tetanic tension to neomycin after an interval of 2 h. It is concluded that neomycin increases the sensitivity of neuromuscular transmission to tubocurarine despite apparently normal responses to indirect stimulation and that the post-tetanic exhaustion observed with neomycin alone may explain apnoea reported in patients with the antibiotic.

4-Aminopyridine reversal of sympathetic ganglionic blockade in the anesthetized cat.

The effects of 4-aminopyridine on the blockades of transmission of the superior cervical ganglion produced by hexamethonium, d-tubocurarine, and polymyxin B were investigated in 15 anesthetized cats. Isometric contractions of the nictitating membrane resulting from pre- and postganglionic stimulation were quantified. A 75-85 per cent ganglionic blockade produced by hexamethonium, 3 mg/kg, or by d-tubocurarine, 1.0 to 1.2 mg/kg, was completely reversed by 4-aminopyridine, 1 mg/kg. After injection of 4-aminopyridine, the times required for the contractions of the nictitating membrane to increase from 25 to 75 per cent of control with preganglionic stimulation were 6 +/- 3 (mean +/- SEM) and 7 +/- 2 min for hexamethonium and d-tubocurarine, respectively. Both values are significantly (P less than 0.05) shorter than their respective control spontaneous recovery times of 26 +/- 8 and 25 +/- 7 min. Polymyxin B, 20-35 mg/kg, depressed the contractions of the nictitating membrane resulting from pre- and postganglionic stimulation by 84 +/- 2 and 66 +/- 10 per cent, respectively. 4-Aminopyridine, 1 mg/kg, lessened the polymyxin B-induced depression of the contractions of the nictitating membrane resulting from preganglionic stimulation to 50 +/- 13 per cent, but had less effect, 61 +/- 13 per cent, on the contractions resulting from postganglionic stimulation. It is concluded that 4-aminopyridine rapidly and completely reverses the sympathetic ganglion blackade produced by hexamethonium or d-tubocurarine, and is partially effective in the reversal of the autonomic effects of polymyxin B.