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ID PMID Title PublicationDate abstract
16174768 The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinas 2006 Jan 1 JAK2, a member of the Janus kinase (JAK) family of protein tyrosine kinases (PTKs), is an important intracellular mediator of cytokine signaling. Mutations of the JAK2 gene are associated with hematologic cancers, and aberrant JAK activity is also associated with a number of immune diseases, including rheumatoid arthritis. Accordingly, the development of JAK2-specific inhibitors has tremendous clinical relevance. Critical to the function of JAK2 is its PTK domain. We report the 2.0 A crystal structure of the active conformation of the JAK2 PTK domain in complex with a high-affinity, pan-JAK inhibitor that appears to bind via an induced fit mechanism. This inhibitor, the tetracyclic pyridone 2-tert-butyl-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinoline-7-1, was buried deep within a constricted ATP-binding site, in which extensive interactions, including residues that are unique to JAK2 and the JAK family, are made with the inhibitor. We present a structural basis of high-affinity JAK-specific inhibition that will undoubtedly provide an invaluable tool for the further design of novel, potent, and specific therapeutics against the JAK family.
20641204 Gd-DOTA-G-NH(CH(2))(11)CO-RSPAYYTAA-(CH(2)CH(2)O)(8)-R. 2004 Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases localized at the cell surface or in extracellular compartments (1). MMPs degrade all components of the extracellular matrix (ECM) and are associated with a variety of pathological conditions such as wound healing, tissue remodeling, tumor angiogenesis, and embryo development. The active site of MMPs contains a catalytic domain coordinated by zinc to recognize motifs with a consensus sequence of PXX↓X(Hy), where ↓ represents the cleavage point and X(Hy) represents a large hydrophobic residue (2). Excess MMP activity has been observed in conjunction with many diseases, including rheumatoid arthritis, osteoarthritis, autoimmune diseases, cardiovascular diseases, and cancer (3). For example, an overexpression of MMP subtype-2 (MMP-2 or gelatinase A), an enzyme that degrades type IV collagen and gelatin, is present in many human tumors (4). Thus, MMP has been an important therapeutic target for many years (5). Gadolinium (Gd)-labeled DOTA-G-NH(CH(2))(11)CO-RSPAYYTAA-(CH(2)CH(2)O)(8)-R (GdPCA2) is a proteinase-modulated contrast agent (PCA) for in vivo imaging of MMP-2 with magnetic resonance imaging (MRI) (6). GdPCA2 consists of four components: a peptide substrate (RSPAY↓YTAA) specific for MMP-2, a Gd-DOTA complex as an MRI probe, an alkyl chain of 12-carbon as a hydrophilic linker between the N-terminus of the peptide and the MRI probe, and an eight-unit polyethylene glycol (PEG(8)) chain linked to the C-terminus of the peptide to enhance the solubility of GdPCA2. The cleavage of GdPCA2 by MMP-2 produces a less soluble Gd(3+)-labeled fragment. Thus, the Gd species acts as a solubility switch specific for the enzyme MMP-2. GdPCA2 may have different pharmacokinetics than its cleaved product, which can be used to evaluate MMP-2 activity via dynamic MRI measurement.
21794423 [Rapid application of infliximab. Efficacy and complications]. 2007 Jul OBJECTIVE: To compare the clinical safety of the rapid infusion of infliximab (30-45 min) with the traditional one (2 h). PATIENTS AND METHOD: Open, prospective study with the consecutive inclusion of 150 patients with rheumatoid arthritis (RA) and/or spondyloarthritis (AS), resistant to conventional treatment. Patients were randomly distributed to receive 1.5 or 3 mg/kg (according to medical criteria) into 2 groups of 75 patients. Group A: patients received a rapid infusion of infliximab (30-45 min) and group B: traditional intravenous infusion (2 h). The rhythm of infusion was regulated through drip counts and the rule of threes and time was counted on a digital chronometer. Data was obtained from all patients included on possible side effects, as well as efficacy parameters (visual analog scale for pain, tender, and swollen joint counts), and comparisons were made between the rapid infusion group and the traditional infusion group. RESULTS: All patients concluded the study without serious complications. In the rapid infusion group 3 patients had hypersensitivity in the infusion arm and erythema was present in 7 more. The presence of side effects was not significantly different in relation with the infusion speed. Differences were not found in relation to the dosage or the type of illness (RA and/or AS) either. The efficacy of Infliximab for symptom control showed no differences using both types of infusion. CONCLUSIONS: The absence of noticeable secondary effects associated with the reduction in the time of infusion of infliximab permits us to point out that a reduction in the time of infusion of infliximab can be a method to optimize hospital resources concerning the outpatient clinic for biologic therapy.
17328054 Novel action of n-3 polyunsaturated fatty acids: inhibition of arachidonic acid-induced in 2007 Mar OBJECTIVE: Neutrophils and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Modulation of TNF receptors (TNFRs) may contribute to the regulation of tissue damage, and n-6 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) can increase the expression of TNFRI and TNFRII on neutrophils. Because the n-3 PUFAs are antiinflammatory in RA, we examined whether, as a novel mechanism of action, n-3 PUFAs can antagonize the AA-induced increase in TNFR expression. METHODS: Human neutrophils were treated with PUFAs and examined for changes in surface expression of TNFRs by flow cytometry. Translocation of protein kinase C (PKC) and activation of ERK-1/2 MAPK were determined by Western blotting. Intracellular calcium mobilization was measured in Fura 2-loaded cells by luminescence spectrometry. RESULTS: Pretreatment of neutrophils with nanomolar levels of n-3 PUFAs, eicosapentaenoic acid, or docosahexaenoic acid led to a marked inhibition of the AA-induced up-regulation of TNFRs I and II. Such pretreatment, however, did not prevent AA from stimulating the activities of PKC and ERK-1/2, which is required for the actions of AA or its ability to mobilize Ca(2+). Nevertheless, treatment with n-3 PUFAs caused the stimulation of serine proteases that could cleave the TNFRs. CONCLUSION: These findings suggest a mechanism by which the n-3 PUFAs inhibit the inflammatory response in RA, by regulating the ability of AA to increase TNFR expression. These results help fill the gaps in our knowledge regarding the mechanisms of action of n-3 PUFAs, thus allowing us to make specific recommendations for the use of n-3 PUFAs in the regulation of inflammatory diseases.
16970805 Factors influencing general practitioner referral of patients developing end-stage renal f 2006 Sep 13 BACKGROUND: To understand why treatment referral rates for ESRF are lower in Ireland than in other European countries, an investigation of factors influencing general practitioner referral of patients developing ESRF was conducted. METHOD: Randomly selected general practitioners (N = 51) were interviewed using 32 standardised written patient scenarios to elicit referral strategies. MAIN OUTCOME MEASURES: General practitioner referral levels and thresholds for patients developing end-stage renal disease; referral routes (nephrologist vs other physicians); influence of patient age, marital status and co-morbidity on referral. RESULTS: Referral levels varied widely with the full range of cases (0-32; median = 15) referred by different doctors after consideration of first laboratory results. Less than half (44%) of cases were referred to a nephrologist. Patient age (40 vs 70 years), marital status, co-morbidity (none vs rheumatoid arthritis) and general practitioner prior specialist renal training (yes or no) did not influence referral rates. Many patients were not referred to a specialist at creatinine levels of 129 micromol/l (47% not referred) or 250 micromol/l (45%). While all patients were referred at higher levels (350 and 480 micromol/l), referral to a nephrologist decreased in likelihood as scenarios became more complex; 28% at 129 micromol/l creatinine; 28% at 250 micromol/l; 18% at 350 micromol/l and 14% at 480 micromol/l. Referral levels and routes were not influenced by general practitioner age, sex or practice location. Most general practitioners had little current contact with chronic renal patients (mean number in practice = 0.7, s.d. = 1.3). CONCLUSION: The very divergent management patterns identified highlight the need for guidance to general practitioners on appropriate management of this serious condition.
16785554 IL-17 plays an important role in the development of experimental autoimmune encephalomyeli 2006 Jul 1 IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17(-/-) murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17(-/-) mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17(-/-) mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17(-/-) CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-gamma(-/-) cells, while IFN-gamma-producing cells were increased in IL-17(-/-) cells, suggesting that IL-17 and IFN-gamma mutually regulate IFN-gamma and IL-17 production. These observations indicate that IL-17 rather than IFN-gamma plays a crucial role in the development of EAE.
16760194 The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis. 2007 Jan OBJECTIVE: To assess whether combined evidence shows the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) C1858T polymorphism and autoimmune diseases, and to summarize the effect size of the polymorphism associated with susceptibility of autoimmune diseases. METHODS: We surveyed studies on the PTPN22 C1858T polymorphism and autoimmune diseases using comprehensive Medline search and review of the references. Meta-analysis was performed for genotypes T/T (recessive effect), T/T + C/T (dominant effect) and T-allele in random effects models. RESULTS: Twenty-nine studies with 43 comparisons including 13 rheumatoid arthritis (RA), six systemic lupus erythematosus (SLE), six type-1 DM (T1D), three Grave's disease (GD), four inflammatory bowel diseases (IBD), three juvenile idiopathic arthritis (JIA), two psoriasis, two multiple sclerosis, two Addison's disease and two Celiac disease were available for the meta-analysis. The overall odds ratios (ORS) for T-allele, T/T and T/T + C/T genotypes were significantly increased in RA, SLE, GD and T1D (OR for T-allele = 1.58, 1.49, 1.85, 1.61, respectively, P < 0.00001). This meta-analysis showed the association between the T-allele and the T/T genotype and JIA (OR = 1.34, P = 0.03; OR = 1.97, P = 0.02) but did not reveal the association between the PTPN22 C1858T polymorphism and IBD, psoriasis, multiple sclerosis, Addison's disease and Celiac disease. CONCLUSION: This meta-analysis demonstrates that the PTPN22 1858T allele confers susceptibility to RA, SLE, GD, T1D and JIA, supporting evidence of association of the PTPN22 gene with subgroup of autoimmune diseases.
18241931 The identification of a small molecule inhibitor that specifically reduces T cell-mediated 2008 Apr 15 Proinflammatory cytokines such as TNFalpha and IL-1beta are produced in lesional skin of chronic plaque psoriasis patients, and at other sites of chronic inflammation such as arthritic joints. They play vital roles in maintaining inflammation. It has recently been suggested that activated T cell contact-mediated monocyte activation, leading to the production of proinflammatory cytokines, contributes to the pathogenesis of psoriasis and other chronic inflammatory diseases such as psoriatic arthritis and rheumatoid arthritis. Using a T cell membrane-monocyte contact bioassay, we have identified small molecule antagonists that differentially block anti-CD3/anti-CD28 activated T cell-mediated, but not LPS-stimulated, TNFalpha production from monocytes. We selected several kinase inhibitors from the Berlex/Schering kinase library and tested the effect of these compounds in blocking TNFalpha production in the T cell membrane-monocyte contact bioassay. We have demonstrated that one compound BLX-1, from a p38 MAP kinase inhibitor project, inhibited T cell-mediated TNFalpha production from monocytes by about 80%, without any effect on TNFalpha production from LPS-stimulated monocytes. Other BLX-1 analogs showed 32-83% inhibition of TNFalpha production with LPS stimulation as compared to almost 100% inhibition of T cell-mediated TNFalpha production. In contrast, PKC inhibitors BLX-5, Go6983, and Ro-31-8220, inhibited TNFalpha production from both activated T cell membrane- and LPS-stimulated monocytes to the same extent (in the range of 50-100% inhibition). Therefore, the activated T cell membrane-monocyte contact bioassay can be used to screen small molecule antagonists that specifically target adaptive but not LPS-mediated innate immunity. Small molecule TNFalpha inhibitors interfering specifically with activated T cell contact-mediated TNFalpha production from monocytes, but not with LPS-mediated TNFalpha production of myeloid cells, are predicted to have an improved side-effect profile and thus may provide more favorable therapeutics for the treatment of T cell-mediated inflammatory diseases.
20477266 Tumor necrosis factor-alpha in severe corticosteroid-refractory asthma. 2007 Aug Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine. Blocking TNF-alpha has been demonstrated to be effective in various diseases, including both rheumatoid and psoriatic arthritis. There is evidence to show that levels of TNF-alpha are elevated in patients with severe asthma. TNF-alpha is involved in the initiation and perpetuation of the inflammatory process, epithelial damage and remodeling, and mucin hypersecretion. Furthermore, TNF-alpha polymorphism has also been reported in the asthmatic population. Based on the necessity for alternative treatments for asthmatics with severe disease and those who are particularly resistant to conventional asthma therapy, it has been shown that molecules targeted at blocking the effects of TNF-alpha probably constitute a considerable advance in the management of these difficult patients. This review focuses on the evidence of TNF-alpha axis upregulation in severe corticosteroid-refractory asthma, as well as the role of TNF-alpha inhibition and the adverse effects of treatment.
18634144 Osteoarticular involvement in a series of 100 patients with sarcoidosis referred to rheuma 2008 Aug OBJECTIVE: To analyze the pattern of osteoarticular lesions in patients with sarcoidosis hospitalized in 4 rheumatology departments. METHODS: We carried out a systematic retrospective analysis of cases with sarcoidosis admitted in the last 10 years, using hospital databases. Two distinct groups were defined from the outset: patients with Löfgren's syndrome (LS) or sarcoid rheumatism (SR). We assessed the following items: distribution of arthritis, chronicity, systemic manifestations, biochemical and immunological measures. RESULTS: We included 100 patients (75% women); 43% had LS and 57% SR. Osteoarticular symptoms revealed the disease in 85% of patients. The patients in the LS group were younger than those in the SR group (41 +/- 9 vs 48 +/- 13 yrs; p < 0.006) and were more likely to have oligoarthritis involving ankles (58% vs 32%; p = 0.04) and high C-reactive protein concentrations (63% vs 33%; p < 0.005). Patients with SR presented osteoarticular symptoms in the form of oligoarthritis (32%), polyarthritis (32%), bony erosion in 8/57 (14%), and osteitis in 9/57 (16%). Lung interstitial involvement was more frequent in the SR group than in the LS group (38% vs 18%; p = 0.03). Chronic polyarthritis was associated with the detection of rheumatoid factor (p = 0.004). Osteitis occurred in older patients (p = 0.02). CONCLUSION: SR was the most frequent manifestation leading to hospitalization; it was characterized by oligoarthritis and polyarthritis and associated with interstitial lung involvement. Osseous involvement occurred in a quarter of SR patients with similar frequency of erosions targeting the distal small bones and osteitis. These latter occurred at a later age.
16337314 Effect of a derivatized tetrapeptide from lactoferrin on nitric oxide mediated matrix meta 2006 Jun Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteolytic enzymes, which degrade several components of extracellular matrix, in arthritic synovial cells. In cultured synovial fibroblasts, both nitric oxide (NO) and reactive oxygen species (ROS) are potent inducers of MMPs production. PEP1261, a tetrapeptide derivative used in this study, corresponds to residues of 39-42 human lactoferrin. The parent protein lactoferrin is able to inhibit the production of free radicals in rheumatoid joints and it regulates many aspects of inflammation. This study is aimed to examine the effects of PEP1261 on MMP-2 production in the presence of nitric oxide donor in cultured synovial fibroblasts from collagen-induced arthritic rats. PEP1261 affects a significant reduction in nitrite levels as well as in MMP-2 production in SNAP stimulated synovial fibroblasts and this is validated by gelatin zymography and immunoblot analysis. Furthermore, RTPCR analysis has demonstrated that PEP1261 inhibits MMP-2 mRNA expression in SNAP treated synovial fibroblasts. The results of this study suggest that PEP1261 possesses antiarthritic activity by inhibiting nitrite levels as well as MMP-2 expression better than control peptides viz., KRDS and RGDS.
17038274 Arthrodesis of the subtalar and talonavicular joints for correction of symptomatic hindfoo 2006 Sep BACKGROUND: Triple arthrodesis has long been used for the treatment of painful malalignment or arthritis of the hindfoot. However, the effect of fusion on adjacent joints has sparked interest in a more limited arthrodesis in patients without involvement of the calcaneocuboid joint. METHOD: Results of 16 feet in 14 patients who had a modified double arthrodesis for symptomatic flatfoot, cavovarus deformity, or hindfoot arthritis were reviewed retrospectively with a minimum followup of 18 (range 18 to 93) months. The most common diagnosis contributing to the hindfoot deformity was pes planovalgus. All operations were done with a consistent technique using rigid internal fixation with screws. In 15 feet, a concomitant gastrocnemius recession for equinus contracture was done at the time of the primary surgery. Clinical evaluation was based on the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale in addition to subjective assessments of pain, function, shoewear, cosmesis, and overall satisfaction. Radiographic evaluation included measurements of the anterior-posterior talo-second metatarsal angle, lateral talocalcaneal angle, and lateral talo-first metatarsal angle, and notation of arthritic changes of the ankle, calcaneocuboid, and midfoot joints, as well as an assessment of time to union of all arthrodeses. RESULTS: The average AOFAS Ankle-Hindfoot Scale improved from 44.7 preoperatively to 77.0 postoperatively (p < 0.01). Subjectively, patients experienced improvements in pain, function, cosmesis, and shoewear. Overall, all patients were satisfied and would have the procedure again under similar circumstances. Radiographically, all parameters statistically improved. There was an increase in arthritic scores for six ankle, six calcaneocuboid, and five midfoot joints. One talonavicular joint nonunion occurred in a rheumatoid patient, requiring revision arthrodesis. CONCLUSIONS: We have concluded that simultaneous arthrodesis of the talonavicular and subtalar joints is a reasonable treatment in the subset of patients with symptomatic hindfoot malalignment whose calcaneocuboid joints are not involved in the primary disease.
18928881 Non-MS autoimmune demyelination. 2008 Nov Connective tissue diseases can be characterised by central nervous system (CNS) involvement, in some patients manifested by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from multiple sclerosis (MS) and other demyelinating processes, such as transverse myelitis and optic neuritis. Demyelinating process may be the feature of nervous impairment in systemic lupus erythematosus, Behcet's disease (BD), Sjoegren's syndrome (SS), systemic sclerosis (SSc) or very rarely other systemic autoimmune diseases. An acute isolated neurological syndrome, as the most common symptom of MS can sometimes be the only feature or even first manifestation of nervous impairment in connective tissue disease, hence presenting the diagnostic problem. Although the white matter abnormalities seen by magnetic resonance imaging may be similar in non-MS autoimmune demyelination and MS, it is the most important diagnostic tool in the differential diagnosis of the mentioned conditions. Investigating the presence of various autoantibodies potentially involved in the pathogenesis of demyelinating lesions as well as cerebrospinal fluid (CSF) analysis can be helpful.
18295675 The IkappaBL gene polymorphism influences risk of acquiring systemic lupus erythematosus a 2008 Jan The human inhibitory kappaB-like gene (IkappaBL) maps to a chromosomal region approximately 25 kb telomeric of the TNF gene at 6p21.3. IkappaBL encodes a protein related to IkappaBalpha that may interact with members of the NF-kappaB/Rel family. We evaluated the role of IkappaBL gene polymorphism in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Genomic DNA isolated from individuals with SLE (n = 134), pSS (n = 67) and from individuals matched for age, sex, and ethnicity (n = 423) was genotyped for Delta-473, -62T/A and +738T/C polymorphisms. The -62A allele was associated with a decrease in the risk of acquiring SLE in a recessive manner; whereas the +738C allele was associated with a more than twofold and threefold increase in the risk of SLE and pSS respectively, relative to the +738T allele. Four haplotypes were observed for the IkappaBL polymorphisms. Haplotype -62A+738T (AT) was associated with a 37% decrease in the risk of SLE, whereas AC tended to increase the risk of developing pSS. Using previously reported TNF data, an almost twofold increased in the risk of SLE was observed between haplotypes IKBL-62T+738T/TNF-308G-238G (TTGG) and TTAG because of linkage disequilibrium between IKBL-62T and TNF-308A. Our findings indicate that the IkappaBL gene influences the risk of developing SLE and pSS.
16505597 [The significance of disease-independence in Mikulicz's disease--revival interests in Miku 2006 Feb Mikulicz's disease represents a unique condition involving enlargement of the lacrimal and salivary glands. Mikulicz's disease has been considered part of primary Sjögren's syndrome because both diseases were histologically similar. However, the gland swellings in Mikulicz's disease are persistent, and its decreased secretional function is good responsiveness to glucocorticoid. Serologically, Mikulicz's disease is characterized by few autoantibody including anti-SS-A and anti-SS-B antibodies. Recently, it is revealed elevated IgG4 concentrations in the serum and prominent infiltration by plasmacytes expressing IgG4 in the lacrimal and salivary glands in Mikulicz's disease. Prominent IgG4-positive plasma cells are also detected in systemic lymph tissues. We cannot detect the phenomenon in Sjögren's syndrome. In complications with Mikulicz's disease, there are autoimmune pancreatitis, retroperitoneal fibrosis, tubulointerstitial nephritis, autoimmune hypophysitis, Riedel's thyroiditis, which are related to IgG4 in its pathogenesis. Mikulicz's disease is different from Sjögren's syndrome, and may be a systemic IgG4-related plasmacytic disease.
18939961 Different proteomic protein patterns in saliva of Sjögren's syndrome patients. 2009 Jan OBJECTIVE: To investigate the salivary protein profile in patients with Sjögren's syndrome (SS), and healthy control subjects. MATERIALS AND METHODS: Unstimulated whole saliva samples were collected from 16 age-matched females; eight healthy subjects and eight patients diagnosed with SS (six primary SS, one incomplete SS and one primary SS associated with B cell lymphoma). Proteins were extracted and separated individually by 2D sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Selected protein spots of interest were analysed by electrospray ionization--tandem mass spectrometry. Obtained data were searched against the Swiss-Prot and NCBI non-redundant protein databases using Mascot software. RESULTS: Two groups of patterns of protein expression were observed in the eight SS patients: a major group (six patients) with significant expression differences from the healthy subjects and the second group (two patients) with a pattern similar to the eight healthy subjects. CONCLUSION: In this preliminary study, protein expression differences were found between SS patients and healthy subjects. Individual analysis of SS patients exhibited two patterns of protein expression with no direct relation to the clinical, serological or histological severity of disease. This study emphasizes the difficulty of the present proteomic knowledge to diagnose and monitor the sequel of SS development.
18008217 [Intrauterine treatment of incomplete fetal heart block in a mother with Sjögren syndrome 2008 Dec BACKGROUND: Isolated fetal heart block is considered as an immunological disorder in the majority of cases. Mothers of affected fetuses often suffer from connective tissue disease (Sjögren syndrome or Lupus erythematodes). All of them test positive for anti-SS-A (anti Ro) and/or anti-SS-B (anti La) antibodies. Once established, third-degree congenital heart block is permanent and often requires a pacemaker. CASE: We report on a pregnancy in a mother with Sjögren syndrome which was complicated by the development of incomplete fetal heart block, diagnosed by pulsed wave Doppler echocardiography. We started oral dexamethasone treatment to reduce immune-mediated fetal cardiac damage and to prevent complications like hydrops fetalis. CONCLUSION: Detection of isolated fetal heart block is possible with pulsed Doppler sonography, but there are no clear recommendations for treatment.
17109806 Hyposalivation in elderly patients. 2006 Nov Saliva is a key element in oral homeostasis, oral function and maintenance of oral health. Dry mouth has multiple oral health consequences and affects quality of life. The incidence of dry mouth and its public health impact are increasing due to the aging population, the effects of some systemic diseases, and medical management and commonly prescribed medications that reduce saliva production. In this paper, we review the causes of dry mouth and its impact on health. The role of dental providers and current management of dry mouth is presented.
18830933 Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sjà 2008 Dec Previous studies have described elevated lipid peroxidase, myeloperoxidase and xanthine oxidoreductase/xanthine oxidase levels on the ocular surface of patients suffering from autoimmune dry eye (Sjögren's syndrome, SS). Reactive oxygen species generated by various enzymatic systems may be dangerous to the eye if they are not sufficiently cleaved by antioxidants. Because antioxidants have not been investigated in dry eye, the aim of this study was to examine the expression of antioxidant enzymes that cleave reactive oxygen species and play a key role in antioxidant protection. Conjunctival epithelial cells of dry eye (SS) patients were obtained by the method of impression cytology using Millicell membranes. Normal eyes served as controls. In the conjunctival epithelium superoxide dismutase, catalase and glutathione peroxidase were examined immunohistochemically. The enzyme expression levels were determined by image analysis and statistical evaluation. In contrast to normal eyes, where antioxidant enzymes were highly expressed in the conjunctival epithelium, in dry eye their expression was much less pronounced in correlation with the increasing severity of dry eye symptoms. Our study suggests that the decreased expression of antioxidant enzymes in dry eye disease (SS) contributes to the development of anterior eye surface oxidative injuries.
17600738 Nitric oxide synthase induction and cytotoxic nitrogen-related oxidant formation in conjun 2007 Aug Until now, the expression and possible role of nitric oxide and nitrogen related oxidants in the human dry eye have not been investigated. Therefore, we examined immunohistochemically nitric oxide synthase isomers (NOS), enzymes generated nitric oxide, nitrotyrosine, a cytotoxic byproduct of nitric oxide and malondialdehyde, a byproduct of lipid peroxidation, in conjunctival epithelium of patients with dry eye, Sjögren's syndrome (SS). Moreover, in conjunctival epithelium of patients with dry eye (SS) the immunohistochemical staining of some pro-inflammatory cytokines was demonstrated: mature interleukin-1 beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha). Conjunctival epithelial cells were obtained by the method of impression cytology. Normal eyes served as controls. In contrast to the normal eyes where endothelial nitric oxide synthase (NOS3) as well as inducible nitric oxide synthase (NOS2) were only slightly expressed in conjunctival epithelium, in dry eye both NOS (mainly NOS2) were gradually expressed along the severity of dry eye symptoms which was in accord with pro-inflammatory cytokine immunodetection (IL-1beta, IL-6, IL-8, TNF-alpha) in dry eye conjunctival cytology samples. This was in contrast to normal eyes where the staining of pro-inflammatory cytokines was weak or completely absent. Peroxynitrite formation (demonstrated by nitrotyrosine residues) and lipid peroxidation (evaluated by increased malondialdehyde staining) were also found in conjunctival epithelium of dry eye with highly pronounced symptoms of dryness. In conclusion, results point to the suggestion that reactive nitrogen species are involved in the pathogenesis or self-propagation of autoimmune dry eye (SS).