Emangiopericitoma Vs Tumore glomico

OBIETTIVI I tumori che originano dalle cellule di supporto dei vasi, i periciti, appartengono alla vasta categoria dei tumori dei tessuti molli che sono lesioni generalmente frequenti nel distretto testa-collo. La trasformazione in senso neoplastico dei periciti è comunque poco frequente e può dare origine a due gruppi neoplastici: i tumori glomici e l’emangiopericitoma. Gli autori presentano in seno alla stessa famiglia due casi clinici rispettivamente di tumori glomico timpanico e di emangiopericitoma del condotto uditivo esterno. MATERIALI I tumori glomici timpanici e giugulari sono rare neoformazioni ipervascolarizzate, a lenta crescita, che si sviluppano nell’ambito dell’orecchio medio e dell’osso temporale; fanno parte di un gruppo di tumori, definiti paragangliomi, che prendono origine da un sistema di cellule derivanti dalla cresta neurale. Esistono delle forme familiari in cui si possono osservare delle lesioni multicentriche, con comparsa sincrona delle lesioni o metacrona, rientrando così in quel gruppo di tumori definito MEN II (neoplasie endocrine multiple tipo II). Ad oggi i loci genici chiamati in causa come responsabili dell’ereditarietà sono definiti: PGL1 codificante per la Succinato Deidrogenasi sub-unità D (SDHD), PGL3 (codificante per SDHC) e PGL4 (codificante per SDHB) localizzati tutti sul cromosoma 11 (11q23-11q13.1). Il locus genico PGL2 non è stato ancora ben identificato. Anche il locus 1q21-q23 può essere responsabile di una forma familiare. L’emangiopericitoma (HPC) è un tumore vascolare maligno che insorge dalle cellule mesenchimali con differenziazione pericitica (periciti di Zimmerman). Il profilo immunoistochimico dell'HPC è incerto e la diagnosi è di solito controversa. La diagnosi differenziale con il sarcoma sinoviale, il condrosarcoma mesenchimale, l'istiocitoma fibroso e il tumore fibroso solitario è problematica. Sono state identificate anomalie cromosomiche (traslocazioni) in alcuni emangiopericitomi in particolare t(x;18)(p11.2;q11.2) ma ad oggi non sono state riscontrate delle forme familiari. RIASSUNTO Gli autori presentano due casi clinici rispettivamente di tumori glomico timpanico e di emangiopericitoma del condotto uditivo esterno di due soggetti appartenenti alla stessa famiglia analizzando le differenti caratteristiche cliniche, audiologiche ed istologiche delle forme neopastiche. CONCLUSIONI Gli autori ipotizzano una origine genetica analoga per le neoplasia sopradescritte che potrebbe essere ricondotta alla inattivazione del gene di Von Hippel-Lindau

A multistage combined approach to promote diabetic wound healing in COVID-19 era

When diabetes mellitus is not properly controlled with drugs and a healthy lifestyle, it exposes patients with advanced peripheral arterial disease or critical limb ischaemia (CLI) to the most serious complications, in particular lower limb ulcers. Surgical or endovascular treatments represent the first line of intervention; in addition, the adequate management of ulcers can guarantee not only a faster wound healing but also the improvement of the patient's prognosis. To speed up this process, negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), and other advanced moist wound dress- ing have been proposed. During Coronavirus disease 2019 (COVID-19) pan- demic, many patients with CLI and diabetes mellitus had difficult access to advanced treatments with a significant reduction in life expectancy. We report the cases of patients with non-healing ulcers and CLI treated with an empiric multistage approach after successful endovascular revascularisation; the post- operative course was eventful in all patients, and foot ulcers are currently in an advanced state of healing. The association between adequate revascularisation, systemic anti-inflammatory, and antibiotic therapy with the multistage advanced medications ensures healing of ulcers, limb salvage, and improvement of patient prognosis

Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver: The Role of eNOS, p38 MAPK, and AMPK Pathways

OBJECTIVE - Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice. RESEARCH DESIGN AND METHODS - The effects of selective CB1 agonist arachidonyl-2-chloroethanolamide (ACEA) and endocannabinoids anandamide and 2-arachidonoylglycerol on endothelial nitric oxide synthase (eNOS) expression were examined, as were mitochondrial DNA amount and mitochondrial biogenesis parameters in cultured mouse and human white adipocytes. These parameters were also investigated in white adipose tissue (WAT), muscle, and liver of mice chronically treated with ACEA. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation was investigated in WAT and isolated mature adipocytes from eNOS-/- and wild-type mice. eNOS, p38 MAPK, adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial biogenesis were investigated in WAT, muscle, and liver of HFD mice chronically treated with ACEA. RESULTS - ACEA decreased mitochondrial biogenesis and eNOS expression, activated p38 MAPK, and reduced AMPK phosphorylation in white adipocytes. The ACEA effects on mitochondria were antagonized by nitric oxide donors and by p38 MAPK silencing. White adipocytes from eNOS-/- mice displayed higher p38 MAPK phosphorylation than wild-type animals under basal conditions, and ACEA was ineffective in cells lacking eNOS. Moreover, mitochondrial biogenesis was downregulated, while p38 MAPK phosphorylation was increased and AMPK phosphorylation was decreased in WAT, muscle, and liver of ACEA-treated mice on a HFD. CONCLUSIONS - CB1 receptor stimulation decreases mitochondrial biogenesis in white adipocytes, through eNOS downregulation and p38 MAPK activation, and impairs mitochondrial function in metabolically active tissues of dietary obese mic

Gynoecium size and ovule number are interconnected traits that impact seed yield

Angiosperms form the biggest group of land plants and display an astonishing diversity of floral structures. The development of the flowers greatly contributed to the evolutionary success of the angiosperms as they guarantee efficient reproduction with the help of either biotic or abiotic vectors. The female reproductive part of the flower is the gynoecium (also called pistil). Ovules arise from meristematic tissue within the gynoecium. Upon fertilization, these ovules develop into seeds while the gynoecium turns into a fruit. Gene regulatory networks involving transcription factors and hormonal communication regulate ovule primordium initiation, their spacing on the placenta, and ovule development. Ovule number and gynoecium size are usually correlated and several genetic factors that impact these traits have been identified. Understanding and fine-tuning the gene regulatory networks influencing ovule number and pistil length opens up strategies for crop yield improvement, which is pivotal in light of a rapidly growing world population. In this review, we present an overview of the current knowledge of the genes and hormones involved in determining ovule number and gynoecium size. We propose a model for the gene regulatory network that guides the developmental processes that determine seed yield

Impact of SARS-CoV-2 on elective surgical volume in Tuscany: effects on local planning and resource prioritization

No abstract availabl

Antinociceptive effects of tetrazole inhibitors of endocannabinoid inactivation: Cannabinoid and non-cannabinoid receptor-mediated mechanisms

Background and purpose: Tetrazoles were recently developed as inhibitors of the cellular uptake of the endocannabinoid anandamide or of its hydrolysis by fatty acid amide hydrolase (FAAH), but were proposed to act also on non-endocannabinoid-related serine hydrolases. Experimental approach: We tested, in a model of inflammatory pain induced in mice by formalin, five chemically similar inhibitors: (i) OMDM119 and OMDM122, two potent carbamoyl tetrazole FAAH inhibitors with no effect on anandamide uptake; (ii) LY2183240, a carbamoyl tetrazole with activity as both FAAH and uptake inhibitor; (iii) OMDM132, a non-carbamoyl tetrazole with activity only as uptake inhibitor and iv) OMDM133, a non-carbamoyl tetrazole with no activity at either FAAH or uptake. Results: All compounds (2.5-10 mg kg -1, i.p.) inhibited the second phase of the nocifensive response induced by intraplantar injection of formalin. The effects of OMDM119, OMDM122 and OMDM133 were not antagonized by pretreatment with cannabinoid CB 1 receptor antagonists, such as rimonabant or AM251 (1-3 mg kg -1, i.p.). The effects of LY2183240 and OMDM132 were fully or partially antagonized by rimonabant, respectively, and the latter compound was also partly antagonized by the CB 2 receptor antagonist, AM630. Conclusions and implications: (i) non-FAAH hydrolases might be entirely responsible for the antinociceptive activity of some, but not all, tetrazole FAAH inhibitors, (ii) the presence of a carbamoylating group is neither necessary nor sufficient for such compounds to act through targets other than FAAH and (iii) inhibition of anandamide uptake is responsible for part of this antinociceptive activity, independently of effects on FAAH. © 2008 Macmillan Publishers Limited All rights reserved

Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice

Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice. In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on dopaminergic signaling at the mesolimbic circuit. By confocal and correlative light and electron microscopy (CLEM) morphological studies coupled to molecular, biochemical, and pharmacological approaches, we investigated OX-A-mediated dopaminergic signaling at the LH-VTA-nucleus accumbens (NAc) pathway in obese ob/ob mice compared to wild-type (wt) lean littermates. We found an elevation of OX-A trafficking and release to the VTA of ob/ob mice and consequent orexin receptor-1 (OX1R)-mediated over-activation of dopaminergic (DA) neurons via phospholipase C (PLC)/diacylglycerol lipase (DAGL-α)-induced biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). In fact, by retrograde signaling to cannabinoid receptor type 1 (CB1R) at inhibitory inputs to DA neurons, 2-AG inhibited GABA release thus inducing an increase in DA concentration in the VTA and NAc of ob/ob mice. This effect was prevented by the OX1R antagonist SB-334867 (30 mg/Kg, i.p.), or the CB1R antagonist AM251 (10 mg/Kg, i.p.) and mimicked by OX-A injection (40 μg/Kg, i.p.) in wt lean mice. Enhanced DA signaling to the NAc in ob/ob mice, or in OX-A-injected wt mice, was accompanied by β-arrestin2-mediated desensitization of dopamine D2 receptor (D2R) in a manner prevented by SB-334867 or the D2R antagonist L741 (1.5 mg/Kg, i.p.). These results further support the role of OX-A signaling in the control of neuroadaptive responses, such as compulsive reward-seeking behavior or binge-like consumption of high palatable food, and suggest that aberrant OX-A trafficking to the DA neurons in the VTA of ob/ob mice influences the D2R response at NAc, a main target area of the mesolimbic pathway, via 2-AG/CB1-mediated retrograde signaling

CB1 Antagonism Exerts Specific Molecular Effects on Visceral and Subcutaneous Fat and Reverses Liver Steatosis in Diet-Induced Obese Mice

International audienceThe beneficial effects of the inactivation of endocannabinoid system (ECS) by administration of antagonists of the cannabinoid receptor (CB) 1 on several pathological features associated with obesity is well demonstrated, but the relative contribution of central versus peripheral mechanisms is unclear. We examined the impact of CB1 antagonism on liver and adipose tissue lipid metabolism in a mouse model of diet-induced obesity. Mice were fed either with a standard diet or a high-sucrose high-fat (HSHF) diet for 19 weeks and then treated with the CB1-specific antagonist SR141716 (10 mg x kg(-1) x day(-1)) for 6 weeks. Treatment with SR141716 reduced fat mass, insulin levels, and liver triglycerides primarily increased by HSHF feeding. Serum adiponectin levels were restored after being reduced in HSHF mice. Gene expression of scavenger receptor class B type I and hepatic lipase was induced by CB1 blockade and associated with an increase in HDL-cholesteryl ether uptake. Concomitantly, the expression of CB1, which was strongly increased in the liver and adipose tissue of HSHF mice, was totally normalized by the treatment. Interestingly, in visceral but not subcutaneous fat, genes involved in transport, synthesis, oxidation, and release of fatty acids were upregulated by HSHF feeding, while this effect was counteracted by CB1 antagonism. A reduction in the CB1-mediated ECS activity in visceral fat is associated with a normalization of adipocyte metabolism, which may be a determining factor in the reversion of liver steatosis induced by treatment with SR141716