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61.
Pasqui AL Di Renzo M Auteri A Federico G Puccetti L 《European journal of clinical investigation》2007,37(9):742-745
BACKGROUND: Inflammatory and/or immune activation occurs both in animal models (twitcher mice) and in the brain of patients with Globoid cell leukodystrophy (GLD) or Krabbe's disease (KD). In this study we evaluated in vitro the cytokine profile of KD patients and the effect of psychosine, the toxic metabolite which plays a role in the demyelination process in these patients. MATERIALS AND METHODS: We studied cytokine production by peripheral blood mononuclear cells (PBMCs) isolated from four KD patients, diagnosed on the basis of clinical criteria. Cells were cultured and stimulated with appropriate agents and the supernatants collected before and after the addition of psychosine. Tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and monocyte chemoattractant factor (MCP)-1) production was evaluated (ELISA method) and compared with a group of 10 normal subjects. RESULTS: We found a significant increase of TNF-alpha release by PBMCs of KD patients compared with healthy subjects; TNF-alpha production was significantly increased after LPS addition. Psychosine was able to induce a further significant increase (P < 0.05) only in cells obtained from KD patients and not from control subjects. No changes were found in IL-8 and MCP-1 production. CONCLUSIONS: The increased TNF-alpha production permits us to confirm the presence of an inflammatory-immune stimulus in KD patients, which may be induced and potentiated by the pathogenetic metabolite psychosine. 相似文献
62.
Andrew W. Silagy Cihan Duzgol Julian Marcon Renzo G. DiNatale Roy Mano Kyle A. Blum Ed Reznik Martin H. Voss Robert J. Motzer Jonathan A. Coleman Paul Russo Oguz Akin A. Ari Hakimi 《Canadian Urological Association journal》2020,14(12):E625
IntroductionNew radiological tools can accurately provide preoperative three-dimensional spatial assessment of metastatic renal cell carcinoma (RCC). We aimed to determine whether the distribution, volume, shape, and fraction of RCC resected in a cytoreductive nephrectomy associates with survival.MethodsWe retrospectively reviewed 560 patients undergoing cytoreductive nephrectomy, performing a comprehensive volumetric analysis in eligible patients of all detectable primary and metastatic RCC prior to surgery. We used Cox regression analysis to determine the association between the volume, shape, fraction resected, and distribution of RCC and overall survival (OS).ResultsThere were 62 patients eligible for volumetric analysis, with similar baseline characteristics to the entire cohort, and median survivor followup was 34 months. Larger primary tumors were less spherical, but not associated with different metastatic patterns. Increased primary tumor volume and tumor size, but not the fraction of tumor resected, were associated with inferior survival. The rank of tumors based on unidimensional size did not completely correspond to the rank by primary tumor volume, however, both measurements yielded similar concordance for predicted OS. Larger tumor volume was not associated with a longer postoperative time off treatment.ConclusionsPrimary tumor volume was significant for predicting OS, while the fraction of disease resected did not appear to impact patient outcomes. Although rich in detail, our study is potentially limited by selection bias. Future temporal studies may help elucidate whether the primary tumor shape is associated with tumor growth kinetics. 相似文献
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65.
Antonio Girolami Antonio Sticchi Alessandro Burul Renzo Dal Bo Zanon 《Vox sanguinis》1977,32(4):230-238
Abstract. 23 patients with hemophilia B have been investigated by means of several immunological methods. 16 patients (69.9%) had no detectable factor XI antigen. Five had a normal factor IX antigen and the electrophoretic mobility of this abnormal factor IX was similar to that of its normal counterpart. One of these five patients had hemophilia BW, since ox brain thromboplastin clotting time was severely prolonged. The remaining two patients had reduced or decreased factor IX antigen. Several patients showed a slight prolongation of ox brain thromboplastin time due to an associated slight factor VII deficiency. On the basis of these results, a tentative classification of hemophilia B into five variants is proposed, namely: hemophilia B, or with no factor IX antigen; hemophilia Bt, or with normal factor IX antigen; hemophilia BRA, or with reduced factor IX antigen; hemophilia BM, or with normal factor TX antigen and severely prolonged ox brain thromboplastin; hemophilia B, usually B-, with associated mild factor VII defect. A complete evaluation of the hemophilia B patients is feasible only by means of a battery of tests, namely: factor TX activity assay, factor IX antigen determination, ox brain thromboplastin clotting time, factor VII activity assay. 相似文献
66.
We report the sixth occurrence of Hb Belfast [beta15(A12)Trp-->Arg], a mild, unstable beta chain variant, in a large family wherein nine subjects were affected. DNA analysis showed a TUG-->AGG mutation at codon 15 of the beta-globin gene, confirming a Trp-->Arg amino acid substitution. The oxygen affinity of the isolated variant was increased. The clinical phenotype is silent or very mild, the only clinical finding being an intermittent moderate jaundice. 相似文献
67.
Belcaro G Cesarone MR Errichi BM Ledda A Di Renzo A Stuard S Dugall M Pellegrini L Rohdewald P Ippolito E Ricci A Cacchio M Ruffini I Fano F Hosoi M 《Angiology》2005,56(6):699-705
Chronic venous insufficiency (CVI) causes a well-defined microangiopathy described as venous hypertensive microangiopathy (VHM) leading to venous ulcerations. VHM is mainly observed in the distal part of the leg, in the perimalleolar region. In VHM edema is the consequence of increased capillary pressure and reduced local clearance, and this affects local perfusion. The healing of venous ulcers is usually very slow. Many treatments are available, but there is still no standard. Oral Pycnogenol is effective in venous disease and particularly in controlling edema. The aim of this study was the evaluation of the local effects of Pycnogenol on ulcers healing associated with venous hypertension. The study lasted 6 weeks including 18 patients (16 completed the study) with venous ulcerations. The oral treatment with Pycnogenol was compared with a combination treatment including oral and local treatment. In subjects treated with the combination treatment (oral and local), venous ulcers healed better (there was a faster reduction in ulcerated area) in comparison with oral treatment only. According to this pilot study Pycnogenol appears to have an important role in local treatment of venous ulcers improving healing and signs/symptoms. 相似文献
68.
Belcaro G Cesarone MR Vinciguerra G Ledda A Dugall M Di Renzo A Stuard S Ricci A Cacchio M Ippolito E Hosoi MF Fano P Spignoli G 《Angiology》2005,56(6):707-713
A medicated plaster containing diclofenac epolamine (DHEP) and heparin has been recently proposed for the treatment of local trauma (ie, ankle sprains) accompanied by a clinically significant edema and/or hematoma formation, based on the combined antiinflammatory, hemorheologic, and antiedema properties of diclofenac and heparin. The aim of this study was therefore to compare the effects of a combined DHEP/heparin and DHEP alone in 2 clinical experimental models of microangiopathy, in order to provide a pharmacologic rationale for association of diclofenac and heparin. The microcirculation was evaluated by measuring cutaneous blood flow (laser Doppler) and transcutaneous oxygen and carbon dioxide pressures (TcPO(2) and TcPCO(2)) in 10 healthy volunteers before and after producing 2 microcirculatory models of microangiopathy: the models were based on reactive hyperemia (RH) and on local histamine injection, which both produce a significant increase in skin flux and alterations of TcPO(2) and TcPCO(2). The area of the study was the distal medial leg, treated with placebo, DHEP alone (Flector Tissugel), and DHEP/heparin (Flector Tissugel Heparin). The plasters were applied before producing the microcirculatory models to evaluate the efficacy of DHEP and DHEP/heparin in controlling and limiting vasodilatation and development of microangiopathy. A significant increase in cutaneous flux was obtained with both models. The application of DHEP partially limited the increase in flux and in TcPCO(2), as well as the decrease in TcPO(2) (which were considered signs of microangiopathy), but the combination DHEP/heparin was significantly more effective than DHEP alone. The inclusion of heparin in the plaster thus improved the control of the microcirculation achieved with diclofenac alone, when an experimental model of venous/arterial hyperemia and microangiopathy was used. In conclusion, DHEP in association with heparin modulates microcirculatory changes better than DHEP alone. It should be interesting to investigate the product in comparable clinical conditions in which it may be useful to act pharmacologically both on inflammation and microcirculatory disturbances that delay the recovery of patients. 相似文献
69.
Research in genetics of epilepsy represents an area of great interest both for clinical purposes and for understanding the basic mechanisms of epilepsy. Most mutations in epilepsies without structural brain abnormalities have been identified in ion channel genes, but an increasing number of genes involved in a diversity of functional and developmental processes are being recognized through whole exome or genome sequencing. Targeted molecular diagnosis is now available for different forms of epilepsy. The identification of epileptogenic mutations in patients before epilepsy onset and the possibility of developing therapeutic strategies tested in experimental models may facilitate experimental approaches that prevent epilepsy or decrease its severity. Functional analysis is essential for better understanding pathogenic mechanisms and gene interactions. In vitro experimental systems are either cells that usually do not express the protein of interest or neurons in primary cultures. In vivo/ex vivo systems are organisms or preparations obtained from them (e.g., brain slices), which should better model the complexity of brain circuits and actual pathophysiological conditions. Neurons differentiated from induced pluripotent stem cells generated from the skin fibroblasts of patients have recently allowed the study of mutations in human neurons having the genetic background of a given patient. However, there is remarkable complexity underlying epileptogenesis in the clinical dimension, as reflected by the fact that experimental models have not provided yet results having clinical translation and that, with a few exceptions concerning rare conditions, no new curative treatment has emerged from any genetic finding in epilepsy. 相似文献
70.
Renzo Guarnieri Rodolfo Reda Dario Di Nardo Gabriele Miccoli Alessio Zanza Luca Testarelli 《Materials》2022,15(5)
Aim: The aim of the present study was to compare the direct and indirect cytotoxicity of a porcine dried acellular dermal matrix (PDADM) versus a porcine hydrated acellular dermal matrix (PHADM) in vitro. Both are used for periodontal and peri-implant soft tissue regeneration. Materials and methods: Two standard direct cytotoxicity tests—namely, the Trypan exclusion method (TEM) and the reagent WST-1 test (4-3-[4-iodophenyl]-2-[4-nitrophenyl]-2H-[5-tetrazolio]-1,3-benzol-desulphonated)—were performed using human primary mesenchymal stem cells (HPMSCs) seeded directly onto a PDADM and PHADM after seven days. Two standard indirect cytotoxicity tests—namely, lactate dehydrogenase (LTT) and MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazoliumbromide)—were performed using HPMSCs cultivated in eluates from the matrices incubated for 0.16 h (10 min), 1 h, and 24 h in a serum-free cell culture medium. Results: The WST and the TEM tests revealed significantly lower direct cytotoxicity values of HPMSCs on the PHADM compared with the PDADM. The indirect cytotoxicity levels were low for both the PHADM and PDADM, peaking in short-term eluates and decreasing with longer incubation times. However, they were lower for the PHADM with a statistically significant difference (p < 0.005). Conclusions: The results of the current study demonstrated a different biologic behavior between the PHADM and the PDADM, with the hydrated form showing a lower direct and indirect cytotoxicity. 相似文献