ABSTRACT
NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), for their maintenance and degenerate rapidly when this activity is lost. However, whether axon survival is regulated by the supply of NAD or by another action of this enzyme remains unclear. Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration. Ectopic expression of NMN deamidase, a bacterial NMN-scavenging enzyme, prolongs survival of injured axons, providing genetic evidence to support such a mechanism. NMN rises prior to degeneration and both the NAMPT inhibitor FK866 and the axon protective protein Wld(S) prevent this rise. These data indicate that the mechanism by which NMNAT and the related Wld(S) protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies.
Subject(s)
Axons/metabolism , Nerve Degeneration/metabolism , Nicotinamide Mononucleotide/metabolism , Peripheral Nerve Injuries/metabolism , Amidohydrolases/pharmacology , Animals , Axons/pathology , Bacterial Proteins/pharmacology , Mice , Nerve Degeneration/drug therapy , Nerve Degeneration/genetics , Nerve Degeneration/pathology , Nicotinamide-Nucleotide Adenylyltransferase/metabolism , Peripheral Nerve Injuries/drug therapy , Peripheral Nerve Injuries/genetics , Peripheral Nerve Injuries/pathologyABSTRACT
AIM: To report original and review existing data on safety and performance of large-needle aspiration biopsy (LNAB) histology in the preoperative selection of palpable thyroid nodule. METHODS AND RESULTS: The English literature and original data were reviewed or analysed. The literature on LNAB of thyroid nodules did not report any complications. A study on needle dimensions has explained why LNAB obtains more tissue than fine-needle aspiration (FNA) and is safe. LNAB histology has higher specificity than FNA cytology and markedly reduces the number of inadequate and indeterminate FNA findings. A comparison of 150 FNA-derived cell blocks with 200 LNAB-derived histological blocks after galectin-3 determination in a large nationwide (Italian) study has shown that one to two sections in 10% of the FNA cell blocks and at least five sections in 90% of the LNAB blocks were available for further determinations of thyroid tumour markers. CONCLUSION: LNAB merits further consideration for the preoperative selection of thyroid nodules.
Subject(s)
Biopsy, Needle/methods , Thyroid Nodule/diagnosis , Thyroid Nodule/pathology , Biomarkers, Tumor/metabolism , Biopsy, Fine-Needle/adverse effects , Biopsy, Fine-Needle/methods , Biopsy, Needle/adverse effects , Galectin 3/metabolism , Humans , Palpation , Safety , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Thyroid Nodule/metabolismABSTRACT
Electroretinographic (ERG) investigations are conventionally performed by using corneal or conjunctival recording electrodes. Both types have to be placed in contact with the eye, resulting invasive and providing discomfort for the patient. This paper presents a simple technique to detect ERG potentials non-invasively. It relies on the use of a conducting liquid between the eye and an external conductor, which actually derives the ocular potential without any ocular contact. These elements are the basic components of a new type of ERG electrode, referred to as Carpi-Tomei (CT) electrode. The paper describes the assembly of prototype samples of the new electrode. Preliminary testing assessed the feasibility of the proposed non-invasive technique.
Subject(s)
Electroretinography/instrumentation , Electroretinography/methods , Adult , Electrodes , Equipment Design , Eye Protective Devices , Female , Humans , Male , Middle Aged , Retina/physiologyABSTRACT
Artificial sensory motor systems are now under development in a truly wearable form using an innovative technology based on electroactive polymers. The integration of electroactive polymeric materials into wearable garments endorses them with strain sensing and mechanical actuation properties. The methodology underlying the design of haptic garments has necessarily to rely on knowledge of biological perceptual and motor processes which is, however, scattered and fragmented. Notwithstanding, the combined use of new polymeric electroactive materials in the form of fibers and fabrics with emerging concepts of biomimetic nature in sensor data analysis, pseudomuscular actuator control and biomechanical design may not only provide new avenues toward the realization of truly wearable kinesthetic and haptic interfaces, but also clues and instruments to better comprehend human manipulative and gestual functions. In this talk the conception, early stage implementation and preliminary testing of a fabric-based wearable interface endowed with spatially redundant strain sensing and distributed actuation are illustrated with reference to a wearable upper limb artificial kinesthesia system, intended to be used in telerehabilitation of post stroke patient.