ABSTRACT
The purpose of this study was to investigate the effects of phosphatidic acid (PA) supplementation on muscle thickness and strength following an 8 week supervised resistance-training program. Fifteen resistance trained men (22.8 ± 3.5 years; 80.6 ± 8.7 kg; 178.1 ± 5.6 cm; 14.6% ± 8.8% body fat) were randomly assigned to a group that either consumed 750 mg of PA or a placebo (PL). Testing was carried out before (PRE) and after (POST) training/supplementation for muscle thickness and strength. Muscle thickness of the rectus femoris (RF), vastus lateralis (VL), biceps brachii (BB), and triceps brachii (TB) muscles were measured via ultrasonography, along with 1 repetition maximum (1RM) of squat, deadlift, and bench press. Analysis of covariance (ANCOVA), using PRE values as the covariate, did not reveal any group differences for measures of muscle thickness in the RF (PA: 3.6% ± 5.2%; PL: 3.2% ± 4.2%, p = 0.97), VL (PA: 23.4% ± 18.1%, PL: 12.5% ± 15.4%, p = 0.37), BB (PA: 3.7% ± 6.4%, PL: 9.6% ± 12.4%, p = 0.86), or TB (PA: 15.1% ± 17.9%, PL: 10.7% ± 19.3%, p = 0.79). Likewise, no group differences were observed in changes in squat (PA: 8.4% ± 4.1%, PL: 8.1% ± 4.2%, p = 0.79), deadlift (PA: 10.1% ± 10.1%, PL: 8.9% ± 9.5%, p = 0.66), or bench press (PA: 5.7% ± 5.5%, PL: 5.1% ± 3.0%, p = 0.76) exercises. Collectively, however, all participants experienced significant (p < 0.05) improvements in each measure of muscle thickness and strength. Results of this study suggest that PA supplementation, in combination with a 3 days·week-1 resistance-training program for 8 weeks, did not have a differential effect compared with PL on changes in muscle thickness or 1RM strength.
Subject(s)
Athletic Performance , Dietary Supplements , Muscle Development , Muscle Strength , Performance-Enhancing Substances/administration & dosage , Phosphatidic Acids/administration & dosage , Resistance Training , Adult , Athletes , Dietary Fats/administration & dosage , Dietary Fats/adverse effects , Dietary Supplements/adverse effects , Double-Blind Method , Humans , Male , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/growth & development , Patient Compliance , Performance-Enhancing Substances/adverse effects , Phosphatidic Acids/adverse effects , Reproducibility of Results , Ultrasonography , Weight Lifting , Young AdultABSTRACT
Pulmonary administration of Toll-like receptor (TLR) ligands protects hosts from inhaled pathogens. However, systemic side effects induced by TLR stimulation limit clinical development. Here, a small-molecule TLR7 ligand conjugated with phospholipid, 1V270 (also designated TMX201), was tested for innate immune activation and its ability to prevent pulmonary infection in mice. We hypothesized that phospholipid conjugation would increase internalization by immune cells and localize the compound in the lungs, thus avoiding side effects due to systemic cytokine release. Pulmonary 1V270 administration increased innate cytokines and chemokines in bronchial alveolar lavage fluids, but neither caused systemic induction of cytokines nor B cell proliferation in distant lymphoid organs. 1V270 activated pulmonary CD11c+ dendritic cells, which migrated to local lymph nodes. However, there was minimal cell infiltration into the pulmonary parenchyma. Prophylactic administration of 1V270 significantly protected mice from lethal infection with Bacillus anthracis, Venezuelan equine encephalitis virus and H1N1 influenza virus. The maximum tolerated dose of 1V270 by pulmonary administration was 75 times the effective therapeutic dose. Therefore, pulmonary 1V270 treatment can protect the host from different infectious agents by stimulating local innate immune responses while exhibiting an excellent safety profile.
Subject(s)
Adenine/analogs & derivatives , Anthrax/drug therapy , Bacillus anthracis/immunology , Communicable Diseases/drug therapy , Dendritic Cells/drug effects , Encephalitis Virus, Venezuelan Equine/immunology , Encephalomyelitis, Venezuelan Equine/drug therapy , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/drug therapy , Lung/drug effects , Orthomyxoviridae Infections/drug therapy , Phosphatidic Acids/adverse effects , Phospholipids/administration & dosage , Purines/administration & dosage , Toll-Like Receptor 7/agonists , Adenine/administration & dosage , Adenine/adverse effects , Adenine/chemical synthesis , Administration, Intranasal , Animals , Anthrax/immunology , Bronchoalveolar Lavage Fluid/immunology , Communicable Diseases/immunology , Cytokines/immunology , Cytokines/metabolism , Dendritic Cells/immunology , Disease Models, Animal , Encephalomyelitis, Venezuelan Equine/immunology , Female , Humans , Immunity, Innate , Influenza, Human/immunology , Injections, Spinal , Ligands , Lung/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Orthomyxoviridae Infections/immunology , Phosphatidic Acids/administration & dosage , Phosphatidic Acids/chemical synthesis , Phospholipids/adverse effects , Phospholipids/chemical synthesis , Purines/adverse effects , Purines/chemical synthesisABSTRACT
The loss of synapses and neurons in Alzheimer's disease (AD) is thought to be at least partly induced by toxic species formed by the amyloid beta (Aß) peptide; therefore, therapeutics aimed at reducing Aß toxicity could be of clinical use for treatment of AD. Liposomes are suitable vehicles for therapeutic agents and imaging probes, and a promising way of targeting the various Aß forms. We tested liposomes functionalized with phosphatidic acid, cardiolipin, or GM1 ganglioside, previously shown to have high Aß-binding capacity. Mimicking Aß-induced toxicity in mouse neuroblastoma cell lines, combined with administration of cell viability-modulating agents, we observed that functionalized liposomes rescued cell viability to different extents. We also detected rescue of the imbalance of GSK-3ß and PP2A activity, and reduction in tau phosphorylation. Thus, these liposomes appear particularly suitable for implementing further therapeutic strategies for AD.
