Gray matter (GM) lesions are recognized as important components of the pathology of multiple sclerosis (MS), and involvement of the deep gray matter (DGM) is suggested by magnetic resonance imaging. ...The aims of this study were to determine the frequency and distribution of lesions and characterize the inflammatory and neurodegenerative changes in DGM of MS patients. Histochemistry, immunohistochemistry, and morphometry were performed on whole coronal sections of 14 MS and 12 control (6 normal, 6 from amyotrophic lateral sclerosis patients) brains. Demyelinating lesions were frequent in MS DGM; most often in the thalamus and caudate, but they were also seen in the putamen, pallidum, claustrum, amygdala, hypothalamus, and substantia nigra. Most DGM lesions involved both GM and white matter. Inflammation in active DGM lesions was similar to that in lesions only in white matter but was less intense, and there was a preponderance of activated microglia, scarce myelin-laden macrophages, and a lesser extent of axonal damage. Neuronal loss was observed both in DGM lesions and nondemyelinated DGM with neuron atrophy in nondemyelinated DGM. In conclusion, demyelination and neurodegenerative changes are common in MS DGM and may contribute to clinical impairment. Inflammation in DGM lesions is intermediate between the destructive inflammation of white matter lesions and the minimal inflammation of cortical lesions. We hypothesize that alterations of glutamate reuptake mechanisms may contribute to these differences.
Abstract An immunological function has been proposed for the choroid plexus (CP). In multiple sclerosis (MS) brains, CPs show (immunohistochemistry to HLA-DR, CD3, CD20, CD68, VCAM-1, CD138) T ...lymphocytes in vessels and stroma, VCAM-1 expression on endothelia, intense HLA-DR immunostaining on cells in CP stroma, among CP epithelium and on epiplexus cells. CPs in control or amyotrophic lateral sclerosis brains do not show such inflammatory changes. Intense CP inflammation is observed in viral encephalitis. Changes in MS CPs suggest persisting immune activation, with intensity similar to acute encephalitis, even in MS phases in which neurodegeneration prevails. In MS, CPs could represent a site for lymphocyte entry in the CSF and for CSF antigens presentation.
Abstract Background and purpose Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the ...clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC. Materials and methods Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m2 ) plus epirubicin (90 mg/m2 ), followed by cisplatin (100 mg/m2 ) and concomitant radiotherapy (70 Gy). Results In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%. Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%. Conclusions NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.
To report the dosimetric data and clinical outcomes of patients with advanced neoplasm of the paranasal sinuses and nasal cavity, treated by three-dimensional conformal radiotherapy.
Between 2000 and ...2005, 31 consecutive patients were treated for locally advanced tumors of paranasal sinuses and nasal cavity. The primary tumor was located as follows: maxillary sinus 15 (48.4%); ethmoid sinus 10 (32.3%); nasal cavity 6 (19.3%). The patients were separated in two groups according to the modality of treatment: group A included 21 patients treated with postoperative three-dimensional conformal radiotherapy with or without chemotherapy; group B included 10 patients treated with radical three-dimensional conformal radiotherapy with or without chemotherapy. The median radiation dose to the planning target volume was 60 Gy (range, 56-63) for patients who underwent complete surgical resection and 68 Gy (range, 64-70) for those who did not have tumor resection or patients with residual disease.
The median follow-up was 42 months. Five-year local tumor control and overall survival actuarial rates were 74% and 72%, respectively, in the postoperative setting, 20% and 25%, respectively, with the primary radiotherapy. Local recurrence was the most common site of failure. No patient developed radio-induced blindness; 4 patients underwent enucleation as part of radical surgery. Dosimetric data are reported.
The local control rate for these tumors remains low. The prognosis depends on localization, tumor stage and treatment modality. Three-dimensional conformal radiotherapy reduces the risk on optical pathways but does not modify outcome.
According to ICHD-II, SIH can be diagnosed in the presence of orthostatic headache and one of the following - neck stiffness, tinnitus, hypoacusia, photophobia, and nausea - or at least one of the ...following - CSF hypotension (<6cm H2O), CSF leakage at neuroimaging, and MRI features of SIH (venous and pituitary engorgement, meningeal thickening, brain sagging, and subdural hygromas) 3. Conservative treatment, which includes hydration, bed rest, and caffeine intake, can be an effective option in many patients, but the recurrence rate seems pointing to high epidural blood patch as a possible effective treatment for SIH.
Evolution led humans to bipedal stance and movement. However, we live in a sedentary society that strongly challenges our willingness to be physically active. We (mis)understand that being at least a ...Sunday runner could protect us from sedentary-related diseases, but what if this compromises the healthier life expectancy anyway? Citing Paul Gauguin, we know where we come from and what we are, the question arises about where we are going. And also, how.
Reactive oxygen species (ROS) are currently recognized as a key driver of several physiological processes. Increasing evidence indicates that ROS levels can affect myogenic differentiation, but the ...molecular mechanisms still need to be elucidated. Protein kinase C (PKC) epsilon (PKCe) promotes muscle stem cell differentiation and regeneration of skeletal muscle after injury. PKCs play a tissue-specific role in redox biology, with specific isoforms being both a target of ROS and an up-stream regulator of ROS production. Therefore, we hypothesized that PKCe represents a molecular link between redox homeostasis and myogenic differentiation. We used an in vitro model of a mouse myoblast cell line (C2C12) to study the PKC-redox axis. We demonstrated that the transition from a myoblast to myotube is typified by increased PKCe protein content and decreased ROS. Intriguingly, the expression of the antioxidant enzyme superoxide dismutase 2 (SOD2) is significantly higher in the late phases of myogenic differentiation, mimicking PKCe protein content. Furthermore, we demonstrated that PKCe inhibition increases ROS and reduces SOD2 protein content while SOD2 silencing did not affect PKCe protein content, suggesting that the kinase could be an up-stream regulator of SOD2. To support this hypothesis, we found that in C2C12 cells, PKCe interacts with Nrf2, whose activation induces SOD2 transcription. Overall, our results indicate that PKCe is capable of activating the antioxidant signaling preventing ROS accumulation in a myotube, eventually promoting myogenic differentiation.
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