Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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17645210 | Standardization of a simple method to study whole saliva: clinical use in different pathol | 2006 | The present study describes a methodology to assess the salivary flow rate in humans. Whole saliva was obtained from the floor of the mouth with a plastic dental ejector and a vacuum pump. Forty healthy subjects of both sexes and 51 patients with different pathologies (Sjögren Syndrome, Thyroid Dysfunction, Diabetes Mellitus) were included in the study. It was demonstrated that basal salivary flow rate was stable five minutes after the insertion of the oral ejector Salivary flow rate did not show significant differences between sexes and was independent of the negative pressure level of the vacuum pump. Stimulated salivary flow rate was quantified over a period of 3 minutes, starting 5 minutes after the introduction of the oral device. The stimulus was paper filter disks soaked in citric acid (2%) placed on the tongue dorsum. The use of this method confirmed the reduction of salivary flow rate in patients with Sjiigren Syndrome. In addition, a significant reduction in salivary flow rate was observed in patients with primary thyroid insufficiency and peripheral neurpathy secondary to Diabetes Mellitus. | |
17408136 | [Systemic pathology and the salivary glands]. | 2006 | Various systemic diseases can affect salivary glands. After a short anatomical and semiological recall, we describe the pathologies according to their possible salivary demonstrations, and we propose in a table a useful memorandum in daily practice. | |
16894414 | Sialocintigraphy versus ultrasonography of the salivary glands in patients first diagnosed | 2006 May | Sjögren's syndrome (SjS) is an autoimmune disease characterized by distraction of particularly salivary and lacrimal glands. The aim of the present study was to compare salivary gland scintigraphy (SGS) and salivary gland ultrasonography (SUS) in identifying salivary gland function in patients first diagnosed with SjS. We recruited 20 such patients with SjS (5 male, 15 female, aged from 35 to 65 y, mean age 52, standard deviation: +/-5 y. All patients were submitted to SUS and SGS longitudinal and transverse images. Before the scintiscan, patients fasted for 6 h. Technetium-99m pertechnetate ((99m)Tc-PT) 110 MBq was injected intravenously (i.v.) and simultaneous multi-frames dynamic acquisition was performed for 30 min. In two patients who had discordant results between SUS and US, labial biopsy was performed. Dynamic acquisition curves for 30 sec for the parotid and the submandibular glands were generated. For each gland we have calculated: (a) the maximum uptake (MU): the ratio between the mean counts in the gland at 20 min and the background activity and (b) the outflow efficiency (OE): the ratio between the minimum counts after lemon juice stimulation at 30 min and the counts at 20 min. The results showed abnormal scintiscans with low MU and high OE in one or more of the glands, in 17/20 patients. These results were confirmed by SUS in 15 cases and in two cases labial biopsy confirmed the diagnosis made by SGS while SUS was negative. In the remaining 3/20 cases of SjS both tests, SUS and SGS, showed normal results. Discrepancies between SGS findings and labial biopsy as found in two of our cases have been reported by others and may be due among other causes to early lymphocytic infiltration in SjS. Normal findings of SGS have also been reported. In conclusion, in cases first diagnosed with SjS, the function of the parotid and the submandibular glands was better identified by the SGS as compared to SUS. Although SGS is a more complex and expensive examination, it should be preferred to SUS as more sensitive and indicating the stage of SjS. | |
16168486 | Lymphocytic infiltration and enlargement of the lacrimal glands: a new subtype of primary | 2005 Nov | PURPOSE: To review the clinical, radiologic, serologic, histopathologic, immunohistochemical, and molecular genetic features of patients having Sjögren's syndrome (SS) with lacrimal gland enlargement. DESIGN: Retrospective case series review. PARTICIPANTS: Fourteen patients histopathologically diagnosed with SS with lacrimal enlargement. Twenty-three age- and gender-matched controls were used for comparison on radiologic analysis. METHODS: Clinical and serologic data were determined directly or by chart review. Computed tomography images from patients were compared with those from the control group. Histopathologic sections were reviewed and graded using the Chisholm-Mason scale, and quantitative immunohistochemical analysis was applied. MAIN OUTCOME MEASURES: Clinically, patients were assessed for age, gender, onset, symptoms and signs, systemic features, treatment, and outcome. Existing histologic specimens were reviewed according to the Chisholm-Mason scale, and then the percentages of plasma cells containing immunoglobulin (Ig) A, IgG, and IgM were determined. Imaging was assessed for lacrimal gland thickness, prolapse, density, and margin contour; extraocular muscle size; orbital tissue displacement; and proptosis. RESULTS: Clinical and histopathological data fulfilled the revised American-European criteria for primary SS in 79% of patients. Compared with other large series of primary SS patients, similarities were found with age, xerophthalmia, parotidomegaly, and articular involvement. Differences included a lower incidence of autoantibodies, xerostomia, and extraglandular features and a higher male-to-female ratio. In almost all patients (93%), the percentage of plasma cells positive for IgA was less than 70%, consistent with SS. Compared with controls, the lacrimal glands were enlarged significantly (P<0.0001) and prolapsed (P<0.001). Involved glands had blurred margins (P<0.007), caused displacement of adjacent tissues (P = 0.03), and were associated with hyperdense fat (P = 0.007). Lymphocytic infiltration of orbital fat was present in all patients for whom fat biopsy results were available. Three patients had monoclonal infiltrates, and 1 patient experienced subsequent extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type, 4 years after presentation. CONCLUSIONS: The criteria used to diagnose primary SS are controversial, but both diagnostic and quantitative immunohistochemical criteria suggest that these patients, with lacrimal gland enlargement resulting from lymphocytic infiltration, represent a new subtype of primary SS. This is clinically important in view of the increased risk of lymphoma associated with SS, compared with idiopathic nonspecific lacrimal inflammation. | |
16322082 | Long term remission of Sjögren's syndrome associated aggressive B cell non-Hodgkin's lymp | 2006 Aug | BACKGROUND: Primary Sjögren's syndrome (SS) is associated with an increased frequency of non-Hodgkin's lymphomas (NHLs), mainly of low histological grade. However, aggressive diffuse large B cell lymphomas (DLBCL) characterised by poor treatment outcome can also be encountered in SS. It has recently been shown that rituxan has significant therapeutic activity in this type of lymphoma. OBJECTIVE: To evaluate the efficacy of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in combination with rituxan in SS patients with DLBCL, and to determine the outcome in such patients. METHODS: In an open, single case trial, six SS patients with DLBCL were assigned to receive eight cycles of CHOP every three weeks plus rituxan given on day 1 of each cycle. In a retrospective study, conducted by the European Concerted Action for SS, nine cases were diagnosed as DLBCL, all of whom had been treated with CHOP alone. These patients were used as historical controls. RESULTS: The difference in the overall survival between the two treatment groups was significant. The group treated with rituxan plus CHOP had a 100% two year overall survival rate, while the historical controls had only a 37% survival rate. Extraglandular manifestations serving as predictors for lymphoma development such as palpable purpura and peripheral neuropathy disappeared. The remission of these signs was accompanied by a decrease in both circulating monoclonal cryoglobulins and rheumatoid factor activity and an increase in C4 levels. Clinically relevant toxicity was not detected. CONCLUSIONS: The addition of rituxan to standard CHOP chemotherapy results in improved treatment outcome in SS patients with aggressive DLBCL, without increasing toxicity. | |
15818675 | Activation of the type I interferon system in primary Sjögren's syndrome: a possible etio | 2005 Apr | OBJECTIVE: The etiopathogenesis of primary Sjögren's syndrome (SS) is largely unknown. In other autoimmune diseases, type I interferon (IFN) may play a pivotal role by triggering and sustaining the disease process. We therefore aimed to determine whether patients with primary SS had an activated type I IFN system. METHODS: Salivary gland biopsy specimens and sera from patients with primary SS were investigated for the occurrence of IFNalpha-producing cells and measurable IFNalpha levels, respectively. The ability of primary SS sera together with apoptotic or necrotic cells to induce IFNalpha production in normal peripheral blood mononuclear cells was examined. The IFNalpha inducer was characterized, and IFNalpha-producing cells were identified. Clinical data were correlated with the IFNalpha-inducing capacity of primary SS sera. RESULTS: Numerous IFNalpha-producing cells were detected in salivary gland biopsy specimens, despite low serum IFNalpha levels. Autoantibodies to RNA-binding proteins, combined with material released by necrotic or late apoptotic cells, were potent inducers of IFNalpha production in plasmacytoid dendritic cells (PDCs). This appeared to be attributable to RNA-containing immune complexes triggering PDCs by means of RNA and interaction with Fcgamma receptor IIa. The IFNalpha-inducing capacity of sera was associated with positive results of a labial salivary gland biopsy (focus score >/=1) and with dermatologic, hematologic, and pulmonary manifestations. CONCLUSION: Patients with primary SS have an activated type I IFN system. Although virus may initiate the production of IFN, the continued IFNalpha synthesis is caused by RNA-containing immune complexes that activate PDCs to prolong IFNalpha production at the tissue level. This IFNalpha promotes the autoimmune process by a vicious circle-like mechanism, with increased autoantibody production and formation of more endogenous IFNalpha inducers. | |
15876427 | The mouse immune response to human fibrinogen reveals an autoimmune component against mous | 2005 Jan | The present experiments were carried out to analyze whether immunization of mice with human fibrinogen would induce autoimmunity like other heterologous proteins such as collagen type II, thyroglobulin or myelin basic protein. Our results demonstrate that human fibrinogen induces very strong immune responses in all mouse strains analyzed. Autoimmune responses with short-term memory to mouse fibrinogen are induced in genetically susceptible mice. These autoimmune Th2-type responses induce splenomegaly, enhanced coagulation times, and production of rheumatoid factors. The short-lived autoimmune memory was not regulated by either suppressor T cells or exhaustion of immune cells; rather this potentially dangerous autoimmune response was regulated by unknown, antigen-specific feedback mechanisms (they do not influence immune responses to proteins like HSA and OA in the same mice). Such feedback mechanisms were not found in the immune responses to other heterologous proteins inducing significant cross-reactive autoimmunity such as collagen type II, thyroglobulin, or myelin basic protein. | |
16354635 | Lacrimal gland orbital lobe cysts associated with MALT lymphoma and primary Sjögren's syn | 2005 Dec | PURPOSE: To describe, for the first time, the occurrence of a large cyst in the orbital lobe of the lacrimal gland in association with marginal zone B-cell MALT lymphoma in three female patients, two of whom also had primary Sjögren's syndrome. METHODS: Retrospective case note review. RESULTS: Three female patients, aged 35, 41 and 47 years, presented with progressive proptosis caused by an enlarging cyst within the orbital lobe of the lacrimal gland. Two of the patients had primary Sjögren's syndrome. Excision of the cyst and part of the lacrimal gland revealed marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type within the gland or wall of the cyst in all cases. The cysts were partially lined by ductular epithelium. One patient had systemic lymphoma, was treated with chemotherapy and remains in remission one year later; the other two had disease apparently confined to the lacrimal gland and are disease-free at 9 months and at three years after local irradiation, respectively. CONCLUSION: To our knowledge, these are the first reported cases of cysts affecting the orbital lobe of the lacrimal gland in patients with B-cell MALT lymphoma of the gland. Although cystic changes have been described in other exocrine glands, lung and thymus in patients with Sjögren's syndrome, this association has also not been described in the lacrimal gland before. | |
15623753 | The relative burden of dry eye in patients' lives: comparisons to a U.S. normative sample. | 2005 Jan | PURPOSE: To assess the relative burden of dry eye in daily life by comparing Short Form-36 (SF-36) responses from individuals with and without dry eye against U.S. norms. METHODS: Assessment of 210 people, 130 with non-Sjogren's keratoconjunctivitis sicca (non-SS KCS), 32 with Sjogren's Syndrome (SS), and 48 control subjects. The study population data and published normative SF-36 data were compared. Dry eye severity was assessed by recruited severity (control, non-SS KCS, SS), patient self-report (none, very mild/mild, moderate, severe/extremely severe), and clinician-report (none, mild, moderate, severe). Age- and gender-matched norms were compared with all defined severity groups. RESULTS: Compared with the norms, control subjects scored higher on all SF-36 scales. Effect size (ES) ranged from 0.15 to 0.52. Non-SS KCS patients had lower Role-Physical (ES=-0.07), Bodily Pain (ES=-0.08), and Vitality (ES=-0.11) scores, indicating more dry eye impact on those areas versus the norm. All SF-36 scale scores except Mental Health (ES=0.12) were lower in the SS group than the adjusted norm (ES range: -0.16 to -0.99). Regardless of severity classification, mild patients consistently had lower Role-Physical and Bodily Pain scores than the norm, suggesting impact on daily roles (ES < 0.2). Patients with moderately severe disease also experienced less vitality and poorer general health. The group with severe disease scored lower than the norm across all domains (ES range: -0.14 to -0.91) except Role-Emotional (ES=0.13) and Mental Health (ES=0.23). CONCLUSIONS: These results indicate dry eye's negative impact on everyday life, particularly in daily activities. Further research using disease-specific measures to examine dry eye's impact is underway. | |
15599353 | Multiple sialolithiasis in the parotid gland with Sjögren's syndrome and its sonographic | 2005 Jan | We present 3 cases of Sjögren's syndrome in which multiple sialolithiasis were observed in the parenchyma of the parotid gland. The sonographic examinations showed microliths that were observed as hyperechoic spots. Some of the microliths were accompanied with comet sign, however most of them showed no particular posterior echoes. None of them showed acoustic shadows, which are normally observed in cases with sialolithiasis. We were able to prove that some of the hyperechoic spots observed sonographically in patients with severe Sjögren's syndrome were microliths. Although these multiple microliths are rarely detected, they may exist potentially in higher frequency in patients with severe Sjögren's syndrome. | |
17522950 | A follow-up study of minimally invasive lip biopsy in the diagnosis of Sjögren's syndrome | 2007 Jul | The aims of this study were to characterize a minimally invasive technique of minor salivary gland biopsy of the lower lip and to present a large patient material undergoing this procedure because of a suspicion of Sjögren's syndrome (SS), as well as to assess the procedure's short-term and long-term value as a diagnostic test and a prognostic factor. The sample consists of consecutive 191 patients undergoing lower lip biopsy in 1987-1990 in Kanta-Hame Central Hospital, Hameenlinna, Finland. The method used was the retrospective chart review. Only three (1.6%) of the biopsies were uninformative, and only one (0.5%) of the patients had a biopsy complication. In 41% of the cases, biopsy was suggestive of SS. Females and elderly patients were more likely to have a positive biopsy result. Surprisingly, a large diversity between pathologists was observed. With the use of focus score instead of older Chisholm classification as an indicator of SS, the specificity of SS diagnostics improved, and the variability between pathologists diminished. Neither SS diagnosis nor positive lip biopsy for SS predicted patients' long-term outcome. In only three patients (1.6%) did the histological diagnosis change due to repeated biopsies. The minimal invasive lower lip biopsy technique presented in this study is a reliable and safe aid in SS diagnostics. The currently recommended histological grading system (focus score > or = 1 suggesting SS) is more specific and reproducible than older Chisholm classification. Repeated biopsy very rarely adds new information. | |
16548837 | Middle lobe syndrome as the pulmonary manifestation of primary Sjögren's syndrome. | 2006 Mar 20 | Middle lobe syndrome - recurrent atelectasis and/or bronchiectasis involving the right middle lobe and/or lingula - has, up to now, not been reported as the pulmonary manifestation of primary Sjögren's syndrome. We describe a patient in whom lymphocytic bronchiolitis in the atelectatic lobes was proved histologically from two separate transbronchial biopsies. The atelectasis responded well to glucocorticoid treatment, suggesting that the peribronchiolar lymphocytic infiltrates may have played an important role in the development of middle lobe syndrome in this patient. | |
16431948 | Conjunctival surface changes in patients with Sjogren's syndrome: a transmission electron | 2006 Feb | PURPOSE: To demonstrate the ultrastructural appearance of the conjunctival surface epithelium in patients with Sjögren's syndrome (SS) compared with normal subjects. METHODS: Conjunctival tissue specimens from seven normal subjects and eight patients with SS were obtained by bulbar conjunctival biopsy and examined by transmission electron microscopy. RESULTS: The average number of microvilli per 8.3 microm epithelial length was significantly lower in the SS group than that in the control group (19.6 +/- 2.5 vs. 28.0 +/- 3.4, P < 0.0001). The microvillus height (0.539 +/- 0.151 microm) and height-width ratio (1.825 +/- 0.549) in the conjunctival epithelium in the SS group were significantly lower than those (height: 0.946 +/- 0.117 microm, P < 0.001; and height-width ratio: 3.717 +/- 0.696, P < 0.0001) in normal individuals. The microvilli in the SS group were wider than those in the control group (P = 0.003). Furthermore, the average number of secretory vesicles (per 8.3 microm epithelial length) in the apical conjunctival epithelial cell was significantly reduced in the SS group (16.4 +/- 6.8 vesicles), compared with the control group (34.7 +/- 1.2 vesicles, P = 0.003). In addition, although the ocular surface glycocalyx (OSG) was always present in control subjects, it was not detectable in all but one of the SS conjunctival specimens. CONCLUSIONS: The ultrastructural morphology of the apical conjunctival epithelium is altered in patients with SS. The findings suggest that an intact OSG may play a key role in the maintenance of a healthy ocular surface, possibly by preventing abrasive influences on the apical epithelial cells. | |
15708895 | Analysis of the insertion/deletion related polymorphism within T cell antigen receptor bet | 2005 Mar | OBJECTIVE: To analyse T cell receptor beta variable (TCRBV) gene polymorphisms (insertion/deletion related polymorphism (IDRP) and BV6S7) in primary Sjögren's syndrome (PSS). METHODS: Genomic DNA was extracted from blood samples from patients fulfilling the modified European criteria for PSS (n = 61). Healthy control blood samples were obtained from the Blood Transfusion Service (n = 121). As a disease control group, samples from patients with systemic lupus erythematosus (n = 42) were analysed. BV6S7 was genotyped using an established PCR/RFLP method. The IDRP was determined by comparison of the intensity of PCR product bands from within BV9S2 and an internal control region (BV9S1), to ascertain whether 0, 1, or 2 copies of the insertion were present. RESULTS: There was a decrease (p = 0.018) in the proportion of PSS patients with the deleted/deleted genotype. There was no association with specific BV6S7 alleles or genotypes with either the PSS group or the hypergammaglobulinaemic subgroup. There were no significant differences in haplotype frequencies after Bonferroni correction. CONCLUSIONS: A reduced proportion of patients with PSS have the deleted/deleted genotype. Eighty nine per cent of PSS patients have at least one extra germline copy of BV13S2*1. This may relate to previous observations of increased BV13 specific T cells and mRNA in the salivary glands. | |
15790714 | Candida albicans peritonitis in a patient with Felty's syndrome. | 2005 Apr | A 53 year old man with Felty's syndrome presented with abdominal pain and fever. He underwent a laparotomy after starting broad spectrum antibiotics. An intestinal biopsy showed skip ulcers with fungal hyphae. Peritoneal exudates grew Candida albicans. He was started on intravenous fluconazole and then switched to liposomal amphotericin to which he showed a good clinical response. After one month at home he was readmitted with candidosis and died of a myocardial infarction. | |
15880319 | Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomiz | 2005 May | BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) might cause hepatic side effects, but the frequency of these laboratory and clinical side effects is uncertain. METHODS: Searches of bibliographic databases MEDLINE and EMBASE and of public archives of the Food and Drug Administration were conducted to identify randomized controlled trials of diclofenac, naproxen, ibuprofen, celecoxib, rofecoxib, valdecoxib, or meloxicam in adults with osteoarthritis or rheumatoid arthritis that provided information on aminotransferase elevations >3 x upper limit of normal, liver-related discontinuations, hepatic serious adverse events, liver-related hospitalizations, or liver-related deaths. The proportion of patients with each of the hepatic toxicity outcomes was calculated separately by using sample size weighted pooling for each NSAID. RESULTS: Sixty-seven articles from the bibliographic database and 65 studies from the Food and Drug Administration archives met inclusion criteria. Diclofenac (3.55%; 95% confidence interval [CI], 3.12%-4.03%) and rofecoxib (1.80%; 95% CI, 1.52%-2.13%) had higher rates of aminotransferase >3 x upper limit of normal than placebo (0.29; 95% CI, 0.17-0.51) and the other NSAIDs (all < or = 0.43%). The 95% CIs for liver-related discontinuations of all NSAIDs except diclofenac (2.17%; 95% CI, 1.78%-2.64%) overlapped with placebo. Only 1 liver-related hospitalization (among 37,671 patients) and 1 liver-related death (among 51,942 patients) occurred, with naproxen. CONCLUSIONS: Diclofenac and rofecoxib had higher rates of aminotransferase elevations than placebo and other NSAIDs studied. No NSAID studied had increased rates of liver-related serious adverse events, hospitalizations, or deaths. | |
15842595 | Immunosuppressive therapy in Whipple's disease patients is associated with the appearance | 2005 May | OBJECTIVES: Whipple's disease is a rare chronic disorder, which is caused by systemic infection with Tropheryma whipplei. The first symptom of Whipple's disease usually is a nondestructive polyarthritis resembling in many aspects seronegative rheumatoid arthritis. This polyarticular inflammatory arthropathy preceding the diagnosis of Whipple's disease for several years frequently is treated with nonsteroidal antiinflammatory drugs (NSAIDs) and with immunosuppressive therapy. There is evidence that altered immune functions play a role in the manifestation of the disease and that Whipple's disease is associated with opportunistic infections. We therefore asked whether immunosuppressive treatment for arthropathy may alter the course of Whipple's disease. PATIENTS AND METHODS: In a series of 27 patients with Whipple's disease clinical data were documented and the patients were followed for 3-4 yr. The patients were classified into three groups according to their medication: (i) patients with immunosuppressive therapy preceding the diagnosis, (ii) patients with NSAIDs before diagnosis, and (iii) patients without such therapies. RESULTS: Arthropathies occurred in the mean 8 yr before diagnosis and were the first symptom in 63% of the patients. Gastrointestinal involvement usually became evident later on and frequently led to the diagnosis of Whipple's disease. In patients with immunosuppressive treatment, diarrhea occurred in the median 4 months after the initiation of such therapy and diagnosis of Whipple's disease was made after another 2 months. In contrast, other medical treatments were not closely followed by the onset of diarrhea. CONCLUSIONS: These results indicate an association between immunosuppressive therapy and the onset of diarrhea in Whipple's disease and thus support the concept that immunologic factors play a role in disease pathogenesis. Further investigation on the interaction of the immune system and Tropheryma whipplei infection are required to understand the factors contributing to the clinical manifestation of this rare disorder and possibly to introduce preventive interventions. | |
16951216 | Vascular endothelial growth factor signaling pathways: therapeutic perspective. | 2006 Sep 1 | The establishment of a vascular supply is one of the earliest and most important events occurring during embryonic development. Growth and maturation of a functional vascular network are complex and still incompletely understood processes involving orchestrated activation of vascular progenitors in the early stages of embryonic development followed by vasculogenesis and angiogenesis. These processes require a tightly regulated activation of several growth factors and their receptors. The role of vascular endothelial growth factors (VEGF) and their receptors has been studied extensively due to their prominent role during blood vessel formation. Mice deficient in various VEGF ligands or receptors show serious defects in vascular formation and maturation. Moreover, members of the VEGF family are involved in other significant biological processes, including lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is released by tumor cells and induces tumor neovascularization. It is now well established that the VEGF axis represents an important target for antitumor therapy. Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis. | |
16920576 | Cyclosporine A for the treatment of autoimmune disorders in HCV infected patients. | 2006 Aug | Due to the relatively high prevalence of both HCV infection and autoimmune disorders (AD), it is not rare to encounter patients with AD also carrying HCV. Considering that the use in HCV infected individuals of corticosteroids or immunosuppressant drugs, that are indeed needed to treat AD, is considered a risk for worsening the clinical outcome of HCV infection, rheumatologist have often refrained from using these drugs in AD when HCV-RNA is also present. Cyclosporine (CsA) is an immunosuppressive agent used to treat a wide range of autoimmune disorders but there is in literature a large body of evidence suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. The anti-HCV effect of CsA has been demonstrated both in vitro and in vivo. Therefore, these evidences have opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases including transplanted ones. Recent reports, although limited in number, also suggest the safety of CsA, in the treatment of patients with AD and concomitant HCV infection. Good results have also been obtained in the treatment in rheumatoid arthritis patients even in association with anti-TNF agents. | |
16633945 | The role of statins in clinical medicine--LDL--cholesterol lowering and beyond. | 2006 Jan 21 | In the past years, statins have emerged as the most important class of lipid lowering agents. Through inhibition of HMG-CoA reductase, they restrict the rate-limiting step of cholesterol synthesis, which leads to upregulation of LDL receptors on the cell membrane and thus reduction of atherogenic LDLs. This effect translates into clinical benefit by reducing cardiovascular events both in primary and secondary prevention settings. As an approximate rule, statin therapy leads to a relative risk reduction of 25-30% in most of the large randomised controlled trials. Stroke risk is reduced to a similar degree. Despite initial concerns, the currently available statins have a favourable safety profile; however, potential interactions with other drugs must be considered. Recently, characteristics unrelated to LDL lowering have been intensively studied. These pleiotropic statin effects result from decreased levels of isoprenoid intermediates of cholesterol synthesis. They include--among others--anti-inflammatory, anti-proliferative, and immunomodulatory actions. Pleiotropic effects favourably influence pathomechanisms of plaque formation. Furthermore, they may prove beneficial in the prevention or treatment of diseases unrelated to atherosclerosis, eg rheumatoid arthritis, multiple sclerosis, or cancer. |