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1.
Nanotechnology ; 28(2): 025102, 2017 Jan 13.
Article in English | MEDLINE | ID: mdl-27922827

ABSTRACT

We report the facile and non-covalent preparation of gold nanoparticles (AuNPs) stabilized by an antiparkinson codrug based on lipoic acid (LA). The obtained AuNPs appear stable in both dimethyl sulfoxide and fetal bovine serum and able to load an amount of codrug double the weight of gold. These NPs were demonstrated to be safe and biocompatible towards primary human blood cells and human neuroblastoma cells, one of the most widely used cellular models to study dopaminergic neural cells, therefore are ideal drug carriers for difficult to solubilize molecules. Very interestingly, the codrug-stabilized AuNPs were shown to reduce the accumulation of reactive oxygen species in SH-SY5Y cells treated with LD and did not change total oxidant status levels in cultured human blood cells, thus confirming the antioxidant role of LA although bound to AuNPs. The characterization of AuNPs in terms of loading and stability paves the way for their use in biomedical and pharmacological applications.


Subject(s)
Antiparasitic Agents , Dopaminergic Neurons/metabolism , Drug Carriers , Gold , Metal Nanoparticles , Adult , Antiparasitic Agents/chemistry , Antiparasitic Agents/pharmacology , Cell Line, Tumor , Dopaminergic Neurons/pathology , Drug Carriers/chemistry , Drug Carriers/pharmacology , Drug Evaluation, Preclinical , Gold/chemistry , Gold/pharmacology , Humans , Male , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Solubility
2.
J Gerontol A Biol Sci Med Sci ; 70(2): 163-73, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24550352

ABSTRACT

Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977).


Subject(s)
Aging/physiology , Exercise/physiology , Muscle Fibers, Skeletal/ultrastructure , Muscle, Skeletal/physiology , Adult , Aged , Biopsy, Needle , Calcium/metabolism , Exercise Test , Humans , Insulin-Like Growth Factor I/genetics , Isometric Contraction/physiology , Male , Membrane Proteins/metabolism , MicroRNAs/genetics , Microscopy, Electron, Transmission , Mitochondria, Muscle/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/pathology , NF-E2-Related Factor 2/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Protein Isoforms/genetics , Proto-Oncogene Proteins/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , Sedentary Behavior , Sterol Regulatory Element Binding Protein 1/metabolism , Transcription Factors/metabolism , Up-Regulation/physiology , YY1 Transcription Factor/metabolism , Young Adult
3.
Spinal Cord ; 46(4): 293-304, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17955034

ABSTRACT

STUDY DESIGN: Unrandomized trial. OBJECTIVES: To investigate the structural and functional relationships and the progression of muscle atrophy up to 20 years of spastic paraplegia. SETTING: Clinical follow-up in Vienna, Austria; muscle biopsies analyzed by light microscopy in Padova and by electron microscopy (EM) in Chieti, Italy. METHODS: Force was measured as knee extension torque; trophism by computer tomography scan; tissue composition and fiber morphology by histopathology and EM. RESULTS: In the long-term group of patients (17.0+/-2.6 years), force and size of thigh muscles were only slightly different from those of mid-term subjects (2.2+/-0.5 years). Histology and ultrastructure confirm that the difference in average size of muscle fibers between long-term and mid-term paralyzed leg muscles is actually very small. In addition, muscle fibers maintain the striated appearance characteristic of normal skeletal fibers even after 14-20 years of paralysis. Ultrastructural alterations of the activating and metabolic machineries, and the presence of fibers with lower motor neuron denervation features, may explain the low-force output and the reduced endurance of paretic muscles. CONCLUSION: The stable muscle atrophy that characterizes long-lasting spastic paraplegia suggests that there are no upper-time limits to begin a training program based on functional electrical stimulation.


Subject(s)
Muscular Atrophy/etiology , Paraplegia/complications , Paraplegia/pathology , Quadriceps Muscle/pathology , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology , Adult , Case-Control Studies , Female , Humans , Male , Muscle Strength/physiology , Muscular Atrophy/diagnostic imaging , Muscular Atrophy/pathology , Paraplegia/physiopathology , Quadriceps Muscle/diagnostic imaging , Quadriceps Muscle/physiopathology , Radiography , Spinal Cord Injuries/physiopathology , Thoracic Vertebrae , Time Factors
4.
Am J Physiol Cell Physiol ; 292(1): C440-51, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17218372

ABSTRACT

Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50-60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of fast fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion.


Subject(s)
Muscle Denervation , Muscle, Skeletal/innervation , Muscle, Skeletal/pathology , Animals , Atrophy , Electric Stimulation , Histocytochemistry , Immunohistochemistry , Microscopy, Electron , Muscle Contraction , Muscle Fibers, Fast-Twitch/pathology , Muscle Fibers, Skeletal/ultrastructure , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , Necrosis , Rabbits , Reaction Time , Sarcomeres/ultrastructure , Time Factors
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