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1.
Patients with Fabry disease on dialysis in the United States. 总被引:9,自引:0,他引:9
Ravi Thadhani Myles Wolf Michael L West Marcello Tonelli Robin Ruthazer Gregory M Pastores Gregorio T Obrador 《Kidney international》2002,61(1):249-255
BACKGROUND.: Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS.: Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS.: During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION.: End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities. 相似文献
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Fraternale A Tonelli A Casabianca A Chiarantini L Schiavano GF Celeste AG Magnani M 《Journal of acquired immune deficiency syndromes (1999)》2000,23(2):107-113
Highly active antiretroviral therapy (HAART), although very efficient in reducing viral load to undetectable levels within 2 weeks, does not eradicate HIV-1 infection and after the suspension of therapy, HIV RNA rebounds to pretherapy levels. This limited efficacy is mainly due to the existence of viral reservoirs such as CD4+ T cells, macrophages, and dendritic cells in which the virus can remain latent. Elimination of these latent reservoirs would be a possible solution to this problem and various efforts are now being directed to this end. With this goal in mind, we investigated a lympholytic drug with known activity against lymphoproliferative malignancies, 2-fluoro-ara-AMP (fludarabine). The murine model of AIDS was used to evaluate the efficacy of alternating administration of fludarabine and azidothymidine (AZT). The aim of this experiment was to eliminate infected cells with fludarabine and protect noninfected cells with AZT. LP-BM5-infected mice were treated with two different therapeutic protocols: one group was treated with two alternating 3-week cycles of fludarabine and AZT (treatment A), whereas the other was treated with three alternating 2-week cycles of fludarabine and AZT (treatment B); both treatments lasted 12 weeks and the animals in the two groups received the same amount of drug. At different times of infection, disease-related findings (i.e., splenomegaly, lymphadenopathy, hypergammaglobulinemia, T-cell and B-cell spleen cell proliferative index, and phenotypes of peripheral blood lymphocytes) were analyzed and the content of proviral DNA in the lymph nodes was quantified. The results obtained show that treatment B was more effective in inhibiting disease progression than treatment A. In fact, all parameters investigated were almost within control values. These results were also confirmed by the quantification of proviral DNA content in the lymph nodes, which after 12 weeks of treatment A declined by approximately 50%, whereas treatment B decreased proviral DNA content by approximately 85% with respect to infected/untreated mice. The data obtained suggest that a therapeutic protocol including three cycles rather than two of a lympholytic drug and antiretroviral drugs is more advantageous. The efficacy of the treatment could likely increase if other drugs were used in addition to AZT and more cycles of fludarabine were added. This approach appears to be of potential interest in an HIV-1 eradication protocol. 相似文献
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Substance P (neurokinin-1) and neurokinin A (neurokinin-2) receptor gene and protein expression in the healthy and inflamed human intestine 总被引:7,自引:0,他引:7 下载免费PDF全文
Renzi D Pellegrini B Tonelli F Surrenti C Calabrò A 《The American journal of pathology》2000,157(5):1511-1522
Increasing evidence suggests that tachykinins are involved in the control of pathophysiological states, such as inflammation. The precise localization of tachykinin receptors is of paramount importance in the search for their possible physiological and pathological role; in this study, therefore, we attempted to define cellular sites of substance P (NK-1R) and neurokinin A (NK-2R) receptor expression in the healthy and the inflamed human intestine by in situ hybridization and immunohistochemistry. In the normal ileum and colon, NK-1R and NK-2R were localized to smooth muscle cells of the muscularis mucosae and propria and a few inflammatory cells of the lamina propria; NK-1R expression was also found in the muscular wall of submucosal blood vessels, enteric neurons and, to a lesser degree, in surface epithelial cells. Patients with Crohn's disease and ulcerative colitis showed a dramatic increase in NK-1R density relative to controls, in both the inflamed and the uninvolved mucosa. Up-regulation of NK-1R was particularly evident on epithelial cells lining the mucosal surface and crypts, as well as on endothelial cells of capillaries and venules. Also, a marked increase in NK-2R expression was found in both groups of patients on inflammatory cells of the lamina propria, especially eosinophils. Our findings demonstrate that in the normal human intestine NK-1R and NK-2R are expressed in multiple cell types, which are endowed with different physiological functions; in addition, they demonstrate that both NK-1R and NK-2R are up-regulated in patients with Crohn's disease and ulcerative colitis. Taken together, these observations may have important physiological and pathophysiological implications, and provide the rationale for the use of NK-1R and NK-2R antagonists in the treatment of inflammatory bowel disease. 相似文献
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The purpose of this work was to study the relative activitiesand stabilities of phase-I and phase-II drug metabolizing enzymesin incubation mixtures used in in vitro genotoxicity testingin order to optimize the conditions of the assay, increase sensitivityand eliminate false negative results. Cytochrome P-450, NADPH-cytochromeP-450 (cytochrome c) reductase activity and various phase-Iand phase-II enzyme activities of the drug-metabolizing systemwere determined in incubation mixtures used in liver microsomalassays. The behaviour of aminopyrine N-demethylase and p-nitroanisoleO-demethylase activities as phase-I markers have been reportedpreviously. Other activities measured were glutathione S-transferase,glutathione S-epoxide transferase and epoxide hydrase, and lipidperoxidation (LP) was determined. The experiments were carriedout on liver S9 fractions derived from non-induced mice or miceinduced with sodium phenobarbital (PB), and/or ß-naphthoflavone(ß-NF). The phase-II enzymes were much more stable(7090% residual activity) than phase-I enzyme activities(3560%) in all conditions tested. The residual cytochromeP-450 was 70% stable and the remaining activity of NADPH-cytochromec-reductase about 80%, indicating that this latter enzyme doesnot limit the rate of the monooxygenase system in these conditions.Phase-II enzymes were induced to a smaller extent (about 2 times)than in phase-I enzymes (56 times) by ß-NF+ PB. NADPH-cytochrome c-reductase behaved as phase-II enzymesin this respect as well as for stability. LP was appreciablyhigher in non-induced than in induced animals. Treatment withthe ß-NF + PB mixture, however, showed that inducedenzymes were more stable than those obtained by simple inductionwith either ß-NF or PB alone. These results lead tothe conclusion that prolonged incubation times in mutagenicityassays are unnecessary when considering the relative stabilitiesof the various phase-I and phase-II enzyme activities in thedrug-metabolizing system. 相似文献
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Alfred K. Cheung Tara I. Chang William C. Cushman Susan L. Furth Fan Fan Hou Joachim H. Ix Gregory A. Knoll Paul Muntner Roberto Pecoits-Filho Mark J. Sarnak Sheldon W. Tobe Charles R.V. Tomson Lyubov Lytvyn Jonathan C. Craig David J. Tunnicliffe Martin Howell Marcello Tonelli Michael Cheung Johannes F.E. Mann 《Kidney international》2021,99(3):559-569
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Ferrari M Scalvini A Losio MN Corradi A Soncini M Bignotti E Milanesi E Ajmone-Marsan P Barlati S Bellotti D Tonelli M 《Journal of virological methods》2003,107(2):205-212
Two pig cell lines derived from kidney and trachea tissues and referred to as newborn swine kidney (NSK) and newborn pig trachea (NPTr) were established following serial culture of primary cells. They were characterized by an epithelial-like morphology, high capacity to replicate and stability of the cell monolayer for several days after seeding. Their modal chromosome number was modified in comparison to that of primary swine cells and they both displayed a transforming potential in vitro and displayed oncogenicity in nude mice. Infection with pig endogenous retroviruses was detected. Almost all the swine viruses tested, i.e., pseudorabies virus, pig parvovirus, hog cholera virus, transmissible gastroenteritis virus of swine, encephalomyocarditis virus, swine vesicular disease virus and the enteroviruses, except pig reproductive respiratory syndrome virus, were capable of replicating in the new cell lines with titres similar to the ones detected in the reference culture systems. Furthermore, all the selected influenza virus sub-types isolated from human, swine and avian species replicated with cytopathic effect in NSK and NPTr cells, whereas, of all the equine influenza viruses tested only the Miami and Suffolk sub-types replicated. 相似文献
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