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ID PMID Title PublicationDate abstract
12352299 Connective tissue diseases and the liver. 2002 Oct Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and scleroderma are systemic disorders that may have an autoimmune basis. The system manifestations vary, and there is frequent overlap among the syndromes. Liver involvement in patients with connective tissue diseases has been well documented but is generally considered rare. Although advanced liver disease with cirrhosis and liver failure is rare in patients with connective tissue diseases, clinical and biochemical evidence of associated liver abnormalities is common. Previous treatment with potentially hepatotoxic drugs or coincident viral hepatitis has usually been implicated as the main causes of liver disease in patients with connective tissue diseases. However, even after careful exclusion of these etiologies, the question remains whether to classify the patient as having a primary liver disease with associated autoimmune, clinical, and laboratory features or as having liver disease as a manifestation of generalized connective tissue disease. The main example of this pathogenetic dilemma is autoimmune hepatitis and SLE-associated hepatitis, which have been regarded as two different entities, although they have features in common of autoimmune syndromes. Several clinical and histopathologic features have been used to discriminate autoimmune hepatitis from SLE, a relevant diagnostic exercise because complications and therapy are quite different. Although hepatic steatosis and abnormal results on biochemical liver function tests are the most common hepatic abnormalities associated with connective tissue diseases, other less frequent abnormalities have been noted, such as nodular regenerative hyperplasia, portal vein obliteration and portal hypertension, features of primary biliary cirrhosis, and rarely portal fibrosis with abnormal lobular architecture. Vascular disorders of the liver also have been described, such as Budd-Chiari syndrome. Histologic assessment may reveal a variety of subclinical liver diseases. The aim of this contribution is to review the current published data regarding liver involvement in connective tissue diseases.
12242080 Genetic and environmental influences on IL-6 and TNF-alpha plasma levels in apparently hea 2002 Aug 7 Dysregulation of cytokines synthesis is thought to play a role in the development of a number of age-related conditions, such as rheumatoid arthritis, osteoporosis, atherosclerosis, and others, but observational studies have led to contradictory results. We investigated potential familial influences on the plasma levels of IL-6 and TNF-alpha in 91 nuclear and more complex pedigrees of Caucasian ethnic origin (N=401 individuals). The maximum likelihood based variance decomposition analysis showed significant positive correlation between circulating IL-6 and age in both genders. The magnitude of these correlations in our sample ranged from 0.22 in females to 0.28 in males (P<0.001). Significant association between TNF-alpha and IL-6 (r=0.28, r=0.43; P<0.001; respectively for men and women) was also observed. Likelihood ratio test clearly revealed that additive genetic effect for TNF-alpha was highly significant (P<0.001), and accounted over 80% of its variation, adjusted for IL-6 levels and age. In contrast, heritability estimate for IL-6 adjusted for age and TNF-alpha, revealed small contribution of genetic factors (24.1 +/- 10.2%). The bivariate variance component analysis demonstrated that significant relationship between IL-6 and TNF-alpha was due to shared environment only (r(E)=0.760 +/- 0.140). As evinced from our complex segregation analysis the nature of the genetic determinant of each of these two cytokines is quite complex and it is probably oligogenic.
12235110 Testing the NKT cell hypothesis of human IDDM pathogenesis. 2002 Sep Defects in IL-4-producing CD1d-autoreactive NKT cells have been implicated in numerous Th1-mediated autoimmune diseases, including diabetes, multiple sclerosis, rheumatoid arthritis, lupus, and systemic sclerosis. Particular attention has been focused on autoimmune insulin-dependent diabetes mellitus (IDDM) because nonobese diabetic (NOD) mice and humans with IDDM are both reported to express severe deficiencies in the frequency and Th2 functions of NKT cells. Furthermore, experimental manipulations of the NKT defect in the NOD mouse induced corresponding changes in disease. Taken together, these converging studies suggested a general role of NKT cells in natural protection against destructive autoimmunity. However, in previous reports the identification of NKT cells was based on indirect methods. We have now devised a direct, highly specific CD1d tetramer-based methodology to test whether humans with IDDM have associated NKT cell defects. Surprisingly, although we find marked and stable differences in NKT cells between individuals, our study of IDDM patients and healthy controls, including discordant twin pairs, demonstrates that NKT cell frequency and IL-4 production are conserved during the course of IDDM. These results contradict previous conclusions and refute the hypothesis that NKT cell defects underlie most autoimmune diseases.
12114254 Neuroimmunoendocrinology of the rheumatic diseases: past, present, and future. 2002 Jun Adaptation to stressful stimuli, maintenance of homeostasis, and ultimately, survival require bidirectional feedback communication among components of the stress response and immune and endocrine systems. Substantial progress has been made in delineating molecular, cellular, and systemic physiologic mechanisms underlying this communication, particularly mechanisms that target the immune system. For example, our understanding of the immunomodulatory activities of numerous neuroendocrine mediators, such as cortisol, estrogen, testosterone, DHEA, catecholamines, corticotropin-releasing hormone, and adenosine, has advanced substantially. Substantial progress has also been made in defining how abnormalities involving these factors may contribute to the initiation, progression, and severity of autoimmune rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). For RA, the available data support the view that inflammatory and immune system inhibitory mechanisms, involving the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system are deficient. Age, gender, and reproductive status acting, in part, through gonadal hormonal effects on disease susceptibility genes also appear likely to modulate the inhibitory stress response systems and immune function. Animal model data also have provided direct evidence that many autoimmune disease regulatory genes are gender influenced. For SLE, a growing body of recent data indicates that estrogens and androgens exert contrasting effects on B-lymphocytes (i.e., estrogens enhance and testosterone suppresses autoantibody production). These observations provide potential new insights into SLE pathogenesis and gender differences in prevalence. Continued investigation will refine our understanding of these observations and will uncover even more extensive interactions of the nervous, immune, and endocrine systems. Moreover, it is highly likely that improved understanding of these interactions will translate into improved therapy for the rheumatic diseases.
12102475 Cyclooxygenase-2 inhibition lacks immunomodulatory effects on T cells. 2002 May OBJECTIVE: In T cells, cyclooxygenase-1 is constitutively expressed, and cyclooxygenase-2 is induced during activation but their functions are not well known. Although exogenous prostaglandins are potent inhibitors of T cell activation, both immunoactivation and immunosuppression have been attributed to cyclooxygenases inhibitors (NSAIDs). Understanding the functions of the cyclooxygenases on T cells is relevant to the therapeutic use of NSAIDs on T cell mediated rheumatic diseases such as rheumatoid arthritis. In this study, we analyze whether cyclooxygenases play a significant role in T cell functions. METHODS: Activation, proliferation, and Fas induced apoptosis were analyzed in T cells treated with non-selective (indomethacin) or cyclooxygenase-2 selective (dimethyl-furanone) inhibitors. Intracellular peroxidation was studied in activated T cells by dihydrorhodamine 123 fluorescence analysis of cells treated with COX-2 antisense or control oligonucleotides. COX-2 expression was analyzed by RT-PCR analysis. RESULTS: Our data show that neither non-selective or selective cyclooxygenase-2 inhibition modify T cell activation, proliferation or apoptosis susceptibility. Furthermore, inhibition of cyclooxygenase-2 expression by antisense oligonucleotides lacks significant effects on T lymphocytes and does not modify their peroxydative capacity. CONCLUSIONS: According to these data, cyclooxygenases do not seem to play a relevant role in T cells functions in vitro. Therefore, the use of either cyclooxygenase-2 selective or non-selective NSAIDs in patients with autoimmune inflammatory diseases is not expected to induce direct immunomodulatory effects through direct effects on T cells.
12076306 Antioxidant/restorative effects of calcined gold preparations used in Indian systems of me 2002 May Stroke, or ischaemic brain damage, is of great geriatric importance being the third most common cause of death after cancer and heart diseases in developed countries. Despite such high frequency, its management has received inadequate attention. Many studies have shown the role of free radicals in the pathogenesis of ischaemic brain damage. Search for safe and effective antioxidant and free radial scavenger agents, therefore, appear to be a promising approach for stroke therapy. Gold, widely used in modern medicine for the treatment of rheumatoid arthritis, is highly valued for various medicinal uses in Indian systems of medicine. Traditional gold preparations are attributed with tonic/rejuvenating and antioxidant properties. Our earlier studies revealed interesting analgesic, immunostimulant, adaptogenic and glycogen sparing properties in these preparations, but their effects in cerebral ischaemia have not been investigated. This prompted us to initiate the present study using global and focal models of ischaemia in albino rats. Enzymatic parameters (lipid peroxidase, reduced glutathione, catalase, glutathione reductase, glutathione-S-transferase, glutatione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase) were employed to assess ischaemic brain damage and its modulation. Significant restoration of altered values to near normal levels by Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan (25 mg/kg, orally for 10 days), suggest potentials for gold preparations in cerebrovascular diseases. The preparations deserve more scientific attention for possible therapeutic exploitation.
11814607 Hypothalamic digoxin related membrane Na+-K+ ATPase inhibition and familial basal ganglia 2002 Jan The isoprenoid pathway produces three key metabolites-digoxin (membrane sodium-potassium ATPase inhibitor and regulator of intracellular calcium-magnesium ratios), dolichol (regulator of N-glycosylation of proteins) and ubiquinone (free radical scavenger). The pathway was assessed in a rare and specific type of familial basal ganglia calcification described. The family had a coexistence of basal ganglia calcification (six out of 10 cases), schizophrenia, Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, systemic tumours and syndrome X and were all right hemispheric dominant. The isoprenoid pathway was also studied for comparison in right hemispheric dominant, bihemispheric dominant and left hemispheric dominant individuals. The isoprenoid pathway was upregulated with increased digoxin synthesis in familial basal ganglia calcification. Membrane sodium-potassium ATPase inhibition can lead on to increase in intracellular calcium and calcification of the basal ganglia. There was increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was also an increase in dolichol and glycoconjugate levels with reduced lysosomal stability in these patients. The ubiquinone levels were low and free radical levels increased. The cholesterol-phospholipid ratio was increased and glycoconjugate level of the RBC membrane reduced in these group of patients. No significance difference was noted in family members with and without basal ganglia calcification. This findings were correlated with the pathogenesis of syndrome X, immune mediated diseases, degenerations, tumours and psychiatric disorders noted in the familial basal ganglia calcification described. The biochemical patterns obtained in familial basal ganglia calcification correlated with those in right hemispheric dominance.
20641300 (111)In-TA138. 2004 Integrins are a family of cell surface heterodimeric glycoproteins that mediate diverse biological events involving cell-cell and cell-matrix interactions (1). They consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor class affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). The α(v)β(3) integrin is strongly expressed on tumor cells, activated endothelial cells (3), and arterial smooth muscle cells (8). In contrast, expression of α(v)β(3) integrin is weak on resting endothelial cells and most normal tissues. The α(v)β(3) antagonists are being studied as anti-tumor and anti-angiogenic agents (4, 9, 10), and the agonists are being studied as angiogenic agents for coronary angiogenesis (11, 12). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) was identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins including α(v)β(3). Various radiolabeled antagonists and peptides were introduced for imaging of tumors and tumor angiogenesis (13). TA138, an antagonist to the α(v)β(3) integrin, was developed based on SH066 (a quinolone-based vitronectin receptor antagonist) (14). TA138 contains a DOTA moiety for (111)In labeling. (111)In-TA138 (RP748) was found to have a high accumulation in a spontaneous mammary adenocarcinoma (α(v)β(3)-positive) in the c-Neu Oncomouse model (14, 15). The binding of (111)In-TA138 to the integrin receptor was found to be specific both in vitro and in vivo.
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.
24115870 Transfer of either index finger extensor tendon to the extensor pollicis longus tendon. 2004 Spring BACKGROUND: Extensor pollicis longus (EPL) tendon ruptures have been treated succesfully with the transfer of the extensor indicis proprius (EIP) tendon. Situations exist in which, due to intraoperative observations, another tendon transfer may be considered preferable to the standard EIP transfer method. OBJECTIVES: To determine whether transfer of the extensor digitorum communis II (EDC II) tendon from the index finger to the EPL tendon, leaving the EIP tendon to the index finger intact, would serve as an equally efficient transfer and not adversely affect the function of the hand. METHODS: Two patients who had the EDC II tendon transferred to the ruptured EPL tendon, and two patients who had the EIP tendon transferred, were retrospectively reviewed. In each transfer type, one patient had suffered an EPL tendon rupture after a Colles' fracture, and the other had rheumatoid arthritis. The rupture occurred on the non-dominant side in one patient in each transfer type. Each patient was examined and subjected to range of motion and power testing at least one year following surgery. RESULTS: All four patients showed a minimal extension lag with the lift off test, but there was no noticeable difference in range of motion, pinch grip and hand grip strength between the transfer types. Both EDC II transfer patients demonstrated an 8° to 15° loss of thumb interphalangeal joint flexion compared with the unoperated side; EIP transfer patients demonstrated less than a 5° loss. Three patients demonstrated a minor extension lag in the index finger and middle finger. Extension power of the thumb and index finger in all patients varied with wrist flexion and extension and ranged from 50% to 150% of the unoperated side. CONCLUSIONS: These case reports suggest that either index finger tendon may be successfully transferred in EPL tendon ruptures.
15266537 Methotrexate for ankylosing spondylitis. 2004 BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. To date, treatment of AS has been limited to the alleviation of symptoms, mainly using non-steroidal anti-inflammatory drugs (NSAIDs). For patients refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Methotrexate (MTX) is currently one of the most widely used DMARDs and its efficacy in rheumatoid arthritis (RA) has been confirmed (Suarez-Almazor 2003). There is uncertainty whether MTX works in the treatment of AS. OBJECTIVES: To evaluate the efficacy and toxicity of methotrexate in the treatment of ankylosing spondylitis. SEARCH STRATEGY: Relevant randomised and quasi-randomised trials in any language were sought using the following sources: CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the reference section of retrieved articles. SELECTION CRITERIA: We evaluated randomised and quasi-randomised trials examining the efficacy of methotrexate on AS. DATA COLLECTION AND ANALYSIS: Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. The methodological quality of included trials were independently assessed by the same reviewers on randomization, concealment, blindness (participants, care providers and outcome investigators), description of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers independently entered the data extracted from the included trials, using RevMan's double entry facility. In the absence of significant heterogeneity, results were combined using weighted mean difference or standardised mean difference for continuous data, and relative risk for dichotomous data. MAIN RESULTS: Two trials met the inclusion criteria. Altan 2001compared naproxen plus MTX (7.5 mg/week orally) with naproxen alone and Roychowdhury 2002 compared MTX (10 mg/week orally) with placebo. The duration of the trials were 12 months and 24 weeks, respectively. They assessed different outcomes except for C-reactive protein (CRP). The included trials treated a total of 81 patients and assessed more than 10 outcomes relevant to the review, covering function, pain, peripheral arthritis/enthesitis, morning stiffness, patient and physician global assessment, CRP and erythrocyte sedimentation rate (ESR). No significant difference between intervention groups was found favouring MTX over no MTX. No serious side effect was reported in either trial. REVIEWERS' CONCLUSIONS: There was no statistically significant benefit of MTX in the examined outcomes for AS patients. High quality, larger sample and longer period of randomized controlled trials (possibly with higher dosage of MTX) are needed to verify the uncertainty about the efficacy and toxicity of MTX for the treatment of AS.
12921755 Ajulemic acid, a nonpsychoactive cannabinoid acid, induces apoptosis in human T lymphocyte 2003 Aug Oral administration of ajulemic acid (AjA), a synthetic nonpsychoactive cannabinoid acid, prevents joint cartilage and bone damage in an experimental model of arthritis in rats. Joint tissue injury in patients with rheumatoid arthritis (RA) is due in part to activation of T lymphocytes in the synovium, and T lymphocytes in synovium of RA patients are resistant to apoptosis. Thus, a potential mechanism whereby AjA prevents joint tissue injury in the animal model might be enhanced apoptosis of T lymphocytes. Apoptosis of human T cells in vitro was assessed by Annexin V expression, caspase-3 activity, DNA fragmentation, and microscopy. AjA induced apoptosis of T cells in a dose- and time-dependent manner. Apoptosis preceded loss of cell viability by trypan blue dye exclusion, confirming that cell loss was due to programmed cell death rather than necrosis. A nontoxic compound such as AjA may be a useful therapeutic agent for patients with diseases such as RA which are characterized by T-cell-driven chronic inflammation and tissue injury.
11840442 Nitric oxide-mediated chondrocyte cell death requires the generation of additional reactiv 2002 Feb OBJECTIVE: Chondrocyte cell death, possibly related to increased production of endogenous nitric oxide (NO), has been observed during the pathogenesis of osteoarthritis and rheumatoid arthritis. The purpose of this study was to investigate the potential role of NO in causing chondrocyte cell death and to determine the contribution of other reactive oxygen species (ROS). METHODS: Cell death and cytotoxicity were evaluated in human articular chondrocytes in response to various NO donor compounds with and without agents that stimulate or inhibit the production of additional ROS using both the alginate bead and the monolayer culture systems. Cell death was quantified by a total cell count with fluorescent labels, and cytotoxicity was measured as a function of cellular NADH- and NADPH-dependent dehydrogenase activity. To determine if the redox status of the chondrocyte could influence the observed effect of NO, cells were preincubated for 24 hours in L-cystine- and glutathione (GSH)-depleted media to reduce intracellular GSH levels, a major defense mechanism against oxidative stress. Apoptosis was analyzed with the quantification of histone-associated DNA fragments. RESULTS: Treatment of chondrocytes with peroxynitrite (ONOO-), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) resulted in apoptotic cell death at concentrations of 0.5 mM, 1.0 mM, and 0.5 mM, respectively. In contrast, treatment of chondrocytes with diazeniumdiolates (or the "NOC" compounds, NOC-5 and NOC-12) at concentrations as high as 2.0 mM did not cause cell death. Furthermore, NOC-5 and NOC-12, at all concentrations tested (0.125-2.0 mM), could prevent cell death caused by oxidative stress. Selective ROS scavengers protected against cell death caused by either SIN-1 or ONOO-; however, no protection could be afforded against the cytotoxicity of SNP with any of the ROS scavengers tested. CONCLUSION: These results show that NO by itself is not cytotoxic to cultured chondrocytes and can even be protective under certain conditions of oxidative stress. Chondrocyte cell death from NO occurs under conditions where other ROS are also generated.
15126673 Spontaneous development of multiple glandular and extraglandular lesions in aged IQI/Jic m 2004 Jul OBJECTIVE: In primary Sjögren's syndrome (SS), systemic exocrine and non-exocrine organs are frequently affected, in addition to the major target tissues of the lacrimal and salivary glands. This study aimed to examine whether the IQI/Jic mouse, an animal model of SS whose autoimmune dacryoadenitis and sialoadenitis have been documented, develops inflammatory lesions in multiple organs as in primary SS. METHODS: Systemic histopathological analysis was performed on IQI/Jic mice at various ages. Phenotypes of infiltrated lymphocytes were determined using immunohistochemical techniques. RESULTS: Inflammatory lesions were observed not only in the lacrimal and salivary glands, but also in multiple organs, including the lung, pancreas and kidney at advanced ages, and were mainly composed of CD4(+) T cells and B cells. The incidence and severity of the inflammatory lesions increased with age in all these organs. The histological appearance and spreading of lesions were similar to those in human primary SS. CONCLUSIONS: IQI/Jic mice spontaneously develop inflammatory cellular infiltrates in multiple exocrine and non-exocrine organs. This characteristic distinguishes IQI/Jic mice from other murine models, making them favourable for studies on the pathogenesis of systemic involvement in primary SS.
12591049 Salivary gland involvement in chronic pancreatitis of various etiologies. 2003 Feb OBJECTIVE: Both the pancreas and salivary glands show many histological and functional similarities. Recently, autoimmune pathogenesis has been postulated in some chronic pancreatitis cases. To examine whether a cell-mediated phenomenon involving the pancreas has a secondary effect on the salivary glands, we assessed the frequency of salivary gland dysfunction in patients with chronic pancreatitis of various etiologies. METHODS: Function of the salivary glands was examined by sialochemistry and salivary gland scintigraphy in patients with chronic pancreatitis (n = 33), Sjogren's syndrome (n = 45), and controls (n = 28). Etiologies of chronic pancreatitis were alcoholic (19 cases), idiopathic (seven cases), and autoimmune (seven cases). RESULTS: Concentrations of Na+, amylase, and beta2-microglobulin in saliva were investigated. In submandibular and parotid gland scintigraphy, time-activity curves were generated, and the ratios of peak count density and washout were calculated. Concentrations of Na+ in saliva of patients with idiopathic chronic pancreatitis and of beta2-microglobulin in saliva of patients with idiopathic and autoimmune chronic pancreatitis were significantly elevated than those of the control group. In submandibular and parotid gland scintigraphy, the peak count density ratio of patients with all chronic pancreatitis and washout ratio of patients with alcoholic and idiopathic chronic pancreatitis were significantly lower than those of the control group. CONCLUSIONS: Salivary gland function was frequently impaired in the course of chronic pancreatitis of various etiologies. Salivary gland dysfunction might be the result of a common pathophysiological effect of alcohol in patients with alcoholic chronic pancreatitis and the aggressive immune mechanism against the pancreatic and the salivary ducts in patients with autoimmune and idiopathic chronic pancreatitis.
15130080 Saliva substitute in xerostomic patients with primary Sjögren's syndrome: a single-blind 2004 May OBJECTIVE: To evaluate the efficacy of oral moisturizing gel (Oral Balance) in xerostomic patients with primary Sjögren's syndrome (SS). METHOD AND MATERIALS: Twenty-one xerostomic patients with primary SS were subjected to a single-blind trial in which the efficacy of Oral Balance gel in reducing xerostomia and xerostomia-related oral symptoms was compared with that of a placebo. Both gels were packaged identically and were indiscernible in appearance and taste. Xerostomia was confirmed for all the patients through measurement of stimulated whole saliva. Patients began using the Oral Balance gel three times a day for 90 days, and were then switched to a gel placebo to be used in the same way for the same length of time. Clinical response was evaluated through the patients' subjective assessment (improved, worsened, or unaltered) of both gels. RESULTS: Neither the Oral Balance gel nor the gel placebo affected the salivary output of the patients. The Oral Balance gel presented a substantial statistically significant advantage in the control of burning mouth, mastication, and swallowing. No statistically significant relief of the isolated sensation of oral dryness was established. CONCLUSION: Oral Balance is a useful tool in the management of dryness-related oral symptoms in primary SS, but there is room for enhancing the overall properties of topical preparations designed to reduce oral complaints in xerostomic patients.
12894386 Therapy of neurological disorders in systemic vasculitis. 2003 Jun Significant progress has been made in our understanding of the underlying cellular and molecular mechanisms associated with vasculitis. Simultaneous involvement of the nervous system and systemic organs points to shared antigenic targets or immune mechanisms operative at both sites. Although specific immunotherapy is not available, the old and new immunomodulatory therapies have been instrumental in providing effective therapy in most of these chronic autoimmune disorders. The treatment of giant cell arteritis, neurosarcoidosis, Wegener's granulomatosis, systemic lupus erythematosus, polyarteritis, Sjögren's syndrome, and Behcet disease will be reviewed.
12879267 Is female predominance in irritable bowel syndrome related to fibromyalgia? 2004 Mar Irritable bowel syndrome (IBS) and fibromyalgia (FM) are common functional diseases in adult women. The aim of this study was to investigate whether female predominance in IBS is related to FM. Fifty patients with IBS and 50 healthy controls were enrolled. All participants answered questionnaires including personal and medical history. In addition, psychiatric interviews were conducted. Patients were divided into two groups according to the coexistence of FM ( IBS+FM or IBS only). The data obtained from patients with or without FM and the control group were compared. There was a significant female predominance in patients with IBS+FM (83.4%, F:M=5:1), but IBS-only patients consisted mainly of males (59.4%, F:M=2:3) ( P<0.01). Comparison of IBS+FM and IBS-only patients showed no significant difference in depression and anxiety status. However, both anxiety and depression scores were found to be higher in female IBS patients than their male counterparts ( P<0.01 and P<0.05, respectively). Our findings suggest that the female predominance in IBS patients may result from coexisting FM.
15453855 The protein kinase C system in focal adenitis of the lacrimal gland in the non-obese diabe 2004 Oct PURPOSE: Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy characterized by hyposecretion of saliva and acinar cell atrophy. As the protein kinase C (PKC) system is involved in the signal transduction pathways associated with primary secretion and acinar cell differentiation and growth, the PKC profile was analysed in NOD mice. METHODS: Lacrimal glands from BALB/c, NOD, NOD scid and transgenic NOD x interferon-gamma (IFN-gamma) mice were analysed for their PKC profiles using antibodies against several conventional (alpha, beta, gamma), novel (delta, epsilon, theta) and atypical (iota, lambda) PKC isoforms using the Streptavidin/HRP (horseradish peroxidase) method. RESULTS: Acinar cells in BALB/c control mice expressed two conventional (alpha, beta) and two atypical (iota, lambda) PKC isoforms. In NOD and transgenic NOD x IFN-gamma mice the same isoforms were more strongly expressed. NOD scid mice lacked all other PKC isoforms except PKC lambda. CONCLUSIONS: Co-expression of several PKC isoforms in single cell type may be necessary for transcriptional activation and agonist-induced secretory responses. Hyposecretion in NOD mice was paradoxically associated with up-regulation of the PKC system. This may be associated with a deranged signal transduction per se rather than with the immune-inflammation, as the transgenic NOD x IFN-gamma mice showed similar PKC profiles. The NOD model does not reproduce lack/consumption of PKC II and PKC as in Sjögren's syndrome. This may be because the receptor autoantibodies in mice are directed against the adrenergic, not muscarinic, receptors. Lack and/or low level PKC expression in NOD scid mouse may explain the excessive acinar cell apoptosis in this model.
15193983 Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteina 2004 Jul BACKGROUND: To investigate the ratio of matrix metalloproteinase (MMP) to tissue inhibitor of metalloproteinase (TIMP) in primary Sjögren's syndrome (PSS), patients and healthy subjects MMP-2, 9 and TIMP-1, 2 levels were measured in saliva. METHODS: Stimulated whole-mixed saliva was collected from 32 patients and 26 healthy subjects. MMP-2, 9 and TIMP-1, 2 levels were measured using enzyme-linked immunosorbent assay (ELISA) and the sandwich enzyme immunoassay (sandwich EIA). Zymography and reverse zymography were used to identify MMPs and TIMPs. RESULTS: MMP-9 (gelatinase-B) level in saliva was significantly increased in the patients. MMP-9 (ng/ml): patients 231.02 +/- 151.77 (mean +/- S.D.), healthy subjects 145.87 +/- 111.65 (p < 0.05). MMP-2 levels were not detected with this system kit in either healthy subjects or patients. The differences in TIMPs were only trends and not statistically significant (p > 0.05). Accordingly, MMP-9/TIMP-1 was greatly increased in the patients (2.60 +/- 1.18) than in the healthy subjects (1.28 +/- 1.11) (p < 0.01). CONCLUSION: This study found that MMP-9/TIMP-1 and MMP-9 levels in the saliva were significantly higher in pSS patients than those in healthy subjects. Our results indicate that the increase in MMP-9/TIMP-1, rather than the increase in MMP-9, in pSS patients' saliva is strongly involved in destruction of glandular and salivary duct tissues.