Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning

Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.We thank FPLD2 patients for donating biological samples. We thank the Italian Network for Laminopathies and the European Consortium of Lipodystrophies (ECLip) for support and helpful discussion. We thank Aurelio Valmori for the technical support. The studies were supported by Rizzoli Orthopedic Institute “5 per mille” 2014 project to MC, AIProSaB project 2016 and Fondazione Del Monte di Bologna e Ravenna grant 2015–2016 “New pharmacological approaches in bone laminopathies based on the use of antibodies neutralizing TGF beta 2” to GL. GL is also supported by PRIN MIUR project 2015FBNB5Y.S

Dielectric spectroscopy - an analytical tool for monitoring the deterioration due to high energy radiation in ethylene propylene diene terpolymer (EPDM) vulcanizates

This paper demonstrates the use of a dielectric spectroscopy technique for monitoring the high energy radiation ageing and stabilization of ethylene propylene diene terpolymer vulcanizates. The measurement of dielectric constants and dielectric losses in the frequency domain help to quantify the physico-chemical changes in the bulk due to high energy irradiation. It is found that the relaxation time calculated using an empirical approach is exponentially related to the total exposed dose. A quantitative comparison of different antirads with a control vulcanizate has been demonstrated by using parameters defined as relative efficiency indices (REI) and relative stability indices (RSI). Three types of REI parameters are defined and computed from dielectric measurements after irradiation over a period of time at a fixed frequency. These REI values are a good estimate of antirad efficiency for energy scavenging and transient charge scavenging. Two types of RSI parameters are defined and computed from the frequency scans of dielectric properties for a material exposed to various doses of gamma irradiation. These RSI values provide a good estimate of the rate and extent of changes in the physico-chemical structure due to irradiation. A third type of RSI, computed from equilibrium swelling measurements, closely matches that obtained from dielectric data. It is concluded that the deterioration is predominantly created by a cross-linking reaction even after the addition of antirads. It is observed that polymeric antirads provide the highest efficiency stability

ACCELERATED AGING AND LIFE TIME PREDICTION ANALYSIS OF POLYMER COMPOSITES - A NEW APPROACH FOR A REALISTIC PREDICTION USING CUMULATIVE DAMAGE THEORY

Service life estimation of polymer materials by accelerated aging is an indispensable tool which provides either a qualitative or quantitative comparison depending on the methodology used. In this paper, a new approach of reliably evaluating the service life in relatively short time durations is described. The proposed method is based on the cumulative damage theory incorporating the statistical treatment of data to provide a realistic output which would be useful for designing products.from selected formulations. It is assumed in this methodology that the overall deterioration of a given material is a cumulative effect of individual deteriorating stresses. It can be computed from the experimental data collected for the aging in various stress conditions, wherein no more than two stresses are accelerated at a time. The aging data obtained from a number of accelerated tests can be analysed using the proposed mathematical equations to simulate the life data for the normal service conditions. This approach is also useful in carrying out comparative studies between two materials with respect to overall performance in the given service environment. The comparison can be either direct or indirect depending on the nature of the product and the service environment selected. The proposed method of modified cumulative damage is described in this paper with all the salient features of the method and its mathematical treatment. A comparison of the proposed approach with other existing methodology is presented to highlight the advantages of the new approach. The experimental work validating the proposed approach and its applications will be described in subsequent publications

Acute carpal tunnel syndrome due to a hemangioma of the median nerve

Hemangioma of the median nerve presenting as acute carpal tunnel syndrome is unusual A-18- year old male presented with severe incapacitating pain of sudden onset of left forearm and hand after manual field work. There was swelling on volar aspect of forearm, with hyperalgesia in the median nerve distribution. The fingers and wrist were inmarked flexion and the patient did not allow wrist and finger extension. X-rays were within normal limits. An emergency volar carpal ligament release revealed, haematoma about 100 ml with numerous vessels encircling the median nerve. Histopathology of lesion turned out to be a cavernous hemangioma. Post operatively patient had full recovery

HIGH-ENERGY RADIATION-RESISTANT ELASTOMERIC VULCANIZATES .1. CHLOROSULFONATED POLYETHYLENE

In this article, a detailed study on the stabilization of chlorosulfonated polyethylene (CSP) vulcanizates in gamma radiation is reported. The special additives (antirads) for the stabilization are synthesized from polynuclear aromatics and formulated in the laboratory. The effect of these antirad formulations on the physicochemical structure and performance properties of these materials is studied by monitoring the degradation in gamma radiation using resistivity, wide-angle X-ray diffraction, and mechanical properties. Antirad formulations to stabilize CSP against a total dosage of 200 Mrads of gamma radiation have been achieved. (C) 199