Degeneration and regeneration of peripheral nerves: role of thrombin and its receptor PAR-1

The peripheral nervous system has a striking regeneration potential and after damage extensive changes in the differentiation state both of the injured neurons and of the Schwann cells are observed. Schwann cells, in particular, undergo a large scale change in gene expression becoming able to support axonal regeneration. Nerve injury is generally associated to inflammation and activation of the coagulation cascade. Thrombin acts as a polyfunctional signalling molecule exerting its physiological function through soluble target proteins and G-protein-coupled receptors, the protease-activated receptors (PARs) [1]. Recently, we have demonstrated that the activation of the main thrombin receptor, PAR-1, in Schwann cells favours their regenerative potential determining the release of factors which promote axonal regrowth [2]. The pro-regenerative potential of thrombin seems to be exerted in a narrow range of concentrations (pM-nM range). In fact, our preliminary data indicate that high levels of thrombin in the micromolar range slow down Schwann cell proliferation and induce cell death. On the contrary, PAR-1 activating peptides mimic the pro-survival but not the pro-apoptotic effects of thrombin. Controlling thrombin concentration may preserve neuronal health during nerve injury and represent a novel target for pharmacologic therapies

Cancer progression: a single cell perspective

Tumor tissues are constituted by a dynamic diversity of malignant and non-malignant cells, which shape a puzzling biological ecosystem affecting cancer biology and response to treatments. Over the course of the tumoral disease, cancer cells acquire genotypic and phenotypic changes, allowing them to improve cellular fitness and overcome environmental and treatment constraints. This progression is depicted by an evolutionary process in which single cells expand as a result of an interaction between single-cell changes and the lovelopments have made it possible to depict the development of cancer at the single-cell level, offering a novel method for understanding the biology of this complex disease. Here, we review those complex interactions from the perspective of single cells and introduce the concept of omics for single-cell studies. This review emphasizes the evolutionary dynamics that control cancer progression and the capacity of single cells to escape the local environment and colonize distant sites. We are assisting a rapid progression of studies carried out at the single-cell level, and we survey relevant single-cell technologies looking at multi-omics studies. These path for precision medicine in cancer

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Age-related changes of monoaminooxidases in rat cerebellar cortex

Age-related changes of the monoaminoxidases, evaluated by enzymatic staining, quantitative analysis of images, biochemical assay and statistical analysis of data were studied in cerebellar cortex of young (3-month-old) and aged (26- month-old) male Sprague-Dawley rats. The enzymatic staining shows the presence of monoamino-oxidases within the molecular and granular layers as well as within the Purkinje neurons of the cerebellum of young and aged animals. In molecular layer, and in Purkinje neurons the levels of monoaminooxidases were strongly increased in old rats. The granular layer showed, on the contrary, an age-dependent loss of enzymatic staining. These morphological findings were confirmed by biochemical results. The possibility that age-related changes in monoaminooxidase levels may be due to impaired energy production mechanisms and/or represent the consequence of reduced energetic needs is discussed

Intracerebral Aspergillus abscess: Case report and review of the literature

Intracranial aspergillosis is a rare pathologic condition, difficult to treat and often fatal, which generally affects immunodepressed patients. A case of brain abscess secondary to pulmonary localization in a patient with a non-Hodgkin lymphoma is described. The most significant clinico-pathological findings of intracranial aspergillosis are examined in the light of the relevant literature

Conjoined lumbosacral nerve roots: observations on three cases and review of the literature

Lumbosacral nerve root anomalies are a rare group of congenital anatomical anomalies. Various types of anomalies of the lumbosacral nerve roots have been documented in the available international literature. Generally speaking, these anomalies may consist of a bifid, conjoined structure, of a transverse course or of a characteristic anastomized appearance. Firstly described as an incidental finding during autopsies or surgical procedures performed for lumbar disk herniations and often asymptomatic, lumbosacral nerve root anomalies have been more frequently described in the last years due to the advances made in radiological diagnosis (metrizamide myelography and CT, MRI). Our study comprised three patients with conjoined lumbosacral nerve roots, representing 0.25% of a total of 1200 patients who underwent lumbosacral CT/MRI procedures in the Addolorata Hospital and in the Service of Neuroradiology of the University of Rome "La Sapienza" during the last three years (March 2001-March 2004). We report our experience with three cases of conjoined lumbosacral nerve roots and analyze the most important literature on this topic. MR imaging is a better diagnostic procedure (in comparison to CT) for the differentiation of nerve root anomalies and, in particular, coronal sections furnish a precise definition of the profile of the conjoined/enlarged rootlets. In fact, the accurate information derived from MRI of multiple planes may be priceless for the preoperative and diagnostic evaluation of lumbosacral nerve root anomalies

Cholinergic innervation of human mesenteric lymphatic vessels

Background: The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity.Materials and methods: Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data.Results: The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods.Conclusions: The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

Manutenção da variabilidade genética de acessos de Bromus auleticus.

Bromus auleticus Trin. ex Nees, cevadilha vacariana, é uma gramínea forrageira nativa considerada de ampla disseminação na América do Sul Temperada, porém de baixa frequência de ocorrência nos campos naturais