Effects of oral L-carnitine supplementation on insulin sensitivity indices in response to glucose feeding in lean and overweight/obese males.

Infusion of carnitine has been observed to increase non-oxidative glucose disposal in several studies, but the effect of oral carnitine on glucose disposal in non-diabetic lean versus overweight/obese humans has not been examined. This study examined the effects of 14 days of L-carnitine L-tartrate oral supplementation (LC) on blood glucose, insulin, NEFA and GLP-1 responses to an oral glucose tolerance test (OGTT). Sixteen male participants were recruited [lean (n = 8) and overweight/obese (n = 8)].

Surface EMG characteristics of people with multiple sclerosis during static contractions of the knee extensors.

Objectives: This study was designed to determine whether any alterations existed in surface electromyography (sEMG) in people with multiple sclerosis (MS) during isometric contractions of the knee extensors.

Methods: Fifteen people with MS and 14 matched controls (mean ± SD age and body mass index 53·7 ± 10·5 versus 54·6 ± 9·6 years and 27·7 ± 6·1 versus 26·5 ± 4, respectively) completed 20%, 40%, 60% and 80% of their maximal voluntary contraction (MVC) of the knee extensors. sEMG was recorded from the vastus lateralis where muscle fibre conduction velocity (MFCV) and sEMG amplitude (RMS) were assessed.

The effect of ankle bracing on peak mediolateral ground reaction force during cutting maneuvers in collegiate male basketball players.

The literature suggests that one-third of ankle injuries sustained during a collegiate basketball season are due to the poor execution of dynamic cutting movements, leading to increased mediolateral force being placed on the unstable ankle. The objective of the present study was to examine the effect of ankle bracing on peak mediolateral ground reaction forces (PMGRF) during sidestep cutting motions in collegiate basketball players. Ten male collegiate basketball players, with no previous history of ankle trauma, performed sidestep cutting motions past a static defensive opponent at speeds between 4.

Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.

A collaborative trial was conducted to evaluate the possibility of integrating the rat-liver Comet assay into repeat-dose toxicity studies. Fourteen laboratories from Europe, Japan and the USA tested fifteen chemicals. Two chemicals had been previously shown to induce micronuclei in an acute protocol, but were found negative in a 4-week Micronucleus (MN) Assay (benzo[a]pyrene and 1,2-dimethylhydrazine; Hamada et al.

The effects of preexisting immunity to influenza on responses to influenza vectors in mice.

The use of viral vectors as vaccine candidates has shown promise against a number of pathogens. However, preexisting immunity to these vectors is a concern that must be addressed when deciding which viruses are suitable for use. A number of properties, including the existence of antigenically distinct subtypes, make influenza viruses attractive candidates for use as viral vectors.

Resting sympathetic nerve activity is related to age, sex and arterial pressure but not to α2-adrenergic receptor subtype.

Objective: Sympathetic nerve hyperactivity has been associated with hypertension and heart failure and their cardiovascular complications. The α2-adrenergic receptors have been proposed to play a prominent role in the control of sympathetic neural output, and their malfunction to constitute a potential central mechanism for sympathetic hyperactivity of essential hypertension. Reports on the relationship between variant alleles of α2-adrenergic receptor subtypes and sympathetic drive or its effects, however, have not been consistent.

Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms.

Background & Aims: Central sensitization is thought to play a role in chronic cough and might explain the temporal association between cough and gastroesophageal reflux (GOR) in patients in whom non-GOR causes have been excluded. Using our novel simultaneous acoustic cough recording and impedance/pH monitoring technique, we aimed to explore this further by assessing such temporal associations and their relationship to the acidity, duration, and proximal extent of reflux and the presence of erosive disease and cough reflex sensitivity in unselected patients (ie, including non-GOR causes) with chronic cough.

Methods: Twenty-four hour ambulatory acoustic cough monitoring with simultaneous impedance/pH recording was carried out in 71 unselected patients with chronic cough, aged 51-64 years (47 female).

Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: implications for dementia risk.

Amyloid-β (Aβ) is secreted as an apolipoprotein of nascent triglyceride-rich lipoproteins (TRL) derived from both liver and intestine, but is better recognized as the principal protein component of senile plaque in subjects with Alzheimer's disease. Recent studies suggest that exaggerated exposure to plasma Aβ can compromise cerebrovascular integrity, resulting thereafter in blood to brain delivery of plasma proteins including TRL-Aβ. Parenchymal deposits of Aβ show significant immunoreactivity to apolipoprotein B (apo B), consistent with the notion of lipoprotein-Aβ entrapment.

Dz13 induces a cytotoxic stress response with upregulation of E2F1 in tumor cells metastasizing to or from bone.

The oligonucleotide Dz13 is a DNA enzyme (deoxyribozyme) that cleaves c-Jun mRNA. It has efficacious effects against tumors directly, is active against tumor-induced angiogenesis, inhibits neointima formation after arterial injury, and controls inflammatory responses. The off-target effects of Dz13 may in fact be driving some of these potentially therapeutic effects, though no mechanisms have been clearly defined in target cells.

Dz13, a c-jun DNAzyme, is a potent inducer of caspase-2 activation.

Signaling pathways for caspase-2-mediated apoptosis are poorly defined. This is partially due to a lack of a reproducible stimulus to trigger caspase-2 activation. We present the oligonucleotide Dz13, a DNA enzyme that cleaves c-Jun mRNA and is capable of inhibiting various model tumors in mice, which potently induces caspase-2 resulting in apoptosis in a panel of tumor cell lines.

Nonclinical safety assessment of the histone deacetylase inhibitor vorinostat.

Vorinostat (SAHA, Zolinza), a histone deacetylase inhibitor, is assessed in nonclinical studies to support its approval for cutaneous T-cell lymphoma. Vorinostat is weakly mutagenic in the Ames assay; is clastogenic in rodent (ie, CHO) cells but not in normal human lymphocytes; and is weakly positive in an in vivo mouse micronucleus assay. No effects are observed on potassium ion currents in the hERG assay up to 300 microM (safety margin approximately 300-fold the approximately 1 microM serum concentration associated with the 400 mg/d maximum recommended human dose.

Dietary fats, cerebrovasculature integrity and Alzheimer's disease risk.

An emerging body of evidence is consistent with the hypothesis that dietary fats influence Alzheimer's disease (AD) risk, but less clear is the mechanisms by which this occurs. Alzheimer's is an inflammatory disorder, many consider in response to fibrillar formation and extracellular deposition of amyloid-beta (Abeta). Alternatively, amyloidosis could notionally be a secondary phenomenon to inflammation, because some studies suggest that cerebrovascular disturbances precede amyloid plaque formation.

Differential effects of dietary fatty acids on the cerebral distribution of plasma-derived apo B lipoproteins with amyloid-beta.

Some dietary fats are a risk factor for Alzheimer's disease (AD) but the mechanisms for this association are presently unknown. In the present study we showed in wild-type mice that chronic ingestion of SFA results in blood-brain barrier (BBB) dysfunction and significant delivery into the brain of plasma proteins, including apo B lipoproteins that are endogenously enriched in amyloid-beta (Abeta). Conversely, the plasma concentration of S100B was used as a marker of brain-to-blood leakage and was found to be increased two-fold because of SFA feeding.

A comparison of two stretching modalities on lower-limb range of motion measurements in recreational dancers.

Most stretching techniques are designed to place a "stress" on the musculoskeletal unit that will increase its resting length and range of motion (ROM). Twenty-four adolescent dancers participated in a 6-week intervention program that compared low-intensity stretching (Microstretching) with moderate-intensity static stretching on active and passive ranges of motion. Microstretching is a new modality that reduces the possibility of the parasympathetic system being activated.

Amyloid-beta colocalizes with apolipoprotein B in absorptive cells of the small intestine.

Background: Amyloid-beta is recognized as the major constituent of senile plaque found in subjects with Alzheimer's disease. However, there is increasing evidence that in a physiological context amyloid-beta may serve as regulating apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider this hypothesis further, this study utilized an in vivo immunological approach to explore in lipogenic tissue whether amyloid-beta colocalizes with nascent triglyceride-rich lipoproteins.

The effect of induced alkalosis and submaximal cycling on neuromuscular response during sustained isometric contraction.

The aim of this study was to determine if inducing metabolic alkalosis would alter neuromuscular control after 50 min of standardized submaximal cycling. Eight trained male cyclists (mean age 32 years, s = 7; [Vdot]O(2max) 62 ml . kg(-1) x min(-1), s = 8) ingested capsules containing either CaCO(3) (placebo) or NaHCO(3) (0.

Single residue deletions along the length of the influenza HA fusion peptide lead to inhibition of membrane fusion function.

A panel of eight single amino acid deletion mutants was generated within the first 24 residues of the fusion peptide domain of the of the hemagglutinin (HA) of A/Aichi/2/68 influenza A virus (H3N2 subtype). The mutant HAs were analyzed for folding, cell surface transport, cleavage activation, capacity to undergo acid-induced conformational changes, and membrane fusion activity. We found that the mutant DeltaF24, at the C-terminal end of the fusion peptide, was expressed in a non-native conformation, whereas all other deletion mutants were transported to the cell surface and could be cleaved into HA1 and HA2 to activate membrane fusion potential.

Myoepithelioma within the carpal tunnel: a case report and review of the literature.

Myoepitheliomas of the extremity are rare and usually benign, while a minority display malignant features. This case demonstrates the diagnosis and management of myoepithelioma within the carpal tunnel. Clinical and radiological tumour features were evaluated.

Permanent and transient effects of locally delivered n-acetyl cysteine in a guinea pig model of cochlear implantation.

Protection of residual hearing after cochlear implant surgery can improve the speech and music perception of cochlear implant recipients, particularly in the presence of background noise. Surgical trauma and chronic inflammation are thought to be responsible for a significant proportion of residual hearing loss after surgery. Local delivery of the anti-oxidant precursor n-acetyl cysteine (NAC) to the cochlea via round window 30min prior to surgery, increased the level of residual hearing at 24-32kHz 4weeks post surgery compared to controls.

A data-based assessment of alternative strategies for identification of potential human cancer hazards.

The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential cancer hazard. Yet experimental evidence shows that cancer is often secondary to a biological precursor effect, the mode of action is sometimes not relevant to humans, and key events leading to cancer in rodents from nongenotoxic agents usually occur well before tumorigenesis and at the same or lower doses than those producing tumors. The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) hypothesized that the signals of importance for human cancer hazard identification can be detected in shorter-term studies.

The -1562C/T MMP-9 promoter polymorphism does not predict MMP-9 expression levels or invasive capacity in saphenous vein smooth muscle cells cultured from different patients.

Matrix metalloproteinase-9 (MMP-9) is an important regulator of vascular smooth muscle cell (SMC) invasion and proliferation. The T allele of the -1562C/T MMP-9 promoter polymorphism reportedly confers increased MMP-9 promoter activity, plasma MMP-9 levels and susceptibility to vascular pathologies. The aim of this study was to determine whether the MMP-9 -1562C/T polymorphism directly influences endogenous MMP-9 expression levels in saphenous vein (SV) SMC cultured from patients with different genotypes.

Polymorphisms of adrenoceptors are not associated with an increased risk of adverse event in heart failure: a MERIT-HF substudy.

Background: Enhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the alpha(2C)-adrenoceptor (Del322-325) polymorphism exclusively or in combination with a beta(1)-adrenoceptor (Arg389) polymorphism, each with known independent effects on sympathetic function, were associated with an increased risk of adverse events in HF.

Methods And Results: A total of 526 patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure study were genotyped for both adrenoceptor polymorphisms.