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ID PMID Title PublicationDate abstract
16507175 B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under sti 2006 B cell-activating factor (BAFF) has a key role in promoting B-lymphocyte activation and survival in primary Sjögren's syndrome (pSS). The cellular origin of BAFF overexpression in salivary glands of patients with pSS is not fully known. We investigated whether salivary gland epithelial cells (SGECs), the main targets of autoimmunity in pSS, could produce and express BAFF. We used quantitative RT-PCR, ELISA and immunocytochemistry in cultured SGECs from eight patients with pSS and eight controls on treatment with IL-10, tumor necrosis factor alpha (TNF-alpha), IFN-alpha and IFN-gamma. At baseline, BAFF expression in SGECs was low in pSS patients and in controls. Treatment with IFN-alpha, IFN-gamma and TNF-alpha + IFN-gamma increased the level of BAFF mRNA in pSS patients (the mean increases were 27-fold, 25-fold and 62-fold, respectively) and in controls (mean increases 19.1-fold, 26.7-fold and 17.7-fold, respectively), with no significant difference between patients and controls. However, in comparison with that at baseline, stimulation with IFN-alpha significantly increased the level of BAFF mRNA in SGECs of pSS patients (p = 0.03) but not in controls (p = 0.2), which suggests that SGECs of patients with pSS are particularly susceptible to expressing BAFF under IFN-alpha stimulation. Secretion of BAFF protein, undetectable at baseline, was significantly increased after IFN-alpha and IFN-gamma stimulation both in pSS patients (40.8 +/- 12.5 (+/- SEM) and 47.4 +/- 18.7 pg/ml, respectively) and controls (24.9 +/- 8.0 and 9.0 +/- 3.9 pg/ml, respectively), with no significant difference between pSS and controls. Immunocytochemistry confirmed the induction of cytoplasmic BAFF expression after stimulation with IFN-alpha and IFN-gamma. This study confirms the importance of resident cells of target organs in inducing or perpetuating autoimmunity. Demonstrating the capacity of SGECs to express and secrete BAFF after IFN stimulation adds further information to the pivotal role of these epithelial cells in the pathogenesis of pSS, possibly after stimulation by innate immunity. Our results suggest that an anti-BAFF therapeutic approach could be particularly interesting in pSS.
15644129 Immunohistochemistry of the B-cell component in lower lip salivary glands of Sjögren's sy 2005 Jan Serial sections of lower lip salivary gland (LSG) biopsies were examined by immunohistochemistry, using a battery of B- and partly T-related antibodies (CD5, CD20, CD21, CD27, CD38, CD45RO, CD79a, Bcl-2 and Bcl-6) in different groups of subjects: healthy controls and clinically verified smoking or nonsmoking cases of primary Sjögren's syndrome (SS). The purpose was to characterize the B-cell pattern of the lymphocytic foci and of the tiny perivascular infiltrates preceding the development of foci. Hyperplastic tonsil was used as stain control. In normal LSG, widely dispersed CD38+ and CD79a+ as well as some CD5+ cells are a normal constituent, with lack of staining with the other antibodies. In SS/LSG, the lymphocytic foci showed staining with all the antibodies, with variable degrees of overlapping or nonoverlapping. In SS/LSG of nonsmokers, CD20+ B cells make up a prominent part of the fully developed periductal lymphocytic foci, not overlapping with CD45RO. Also, CD20+ B cells did not overlap in the infiltrates with colocalized CD27+/CD38+ cells. CD20+ B cells and CD45RO+ T cells also occur as minute infiltrates perivascularly in areas of no foci in SS/LSG as well as in SS smokers lacking the typical foci. Smokers lack foci, but tiny infiltrates express CD20 as well CD45R0. Our findings suggest that CD20+ B cells and CD45RO+ T cells are early immigrants in the LSG of SS of smokers as well as nonsmokers and that another subgroup of CD27+/CD38+ B cells gradually mix with the first two to form the characteristic foci in SS/LSG. The simultaneous demonstration of CD20+ and CD27+ B cells in SS/LSG may constitute a significant diagnostic tool. Further, the findings suggest that the early immigrating lymphocytes may have been primed at a site remote from the glands before arriving via the blood to the gland tissue.
16334882 [Membranous glomerulonephritis during primary Gougerot-Sjögren syndrome]. 2005 Sep 10 INTRODUCTION: Glomerulonephritis, mainly membranoproliferative or membranous (MG), is observed much less often than interstitial involvement in Sjögren's syndrome (SS). CASE: We report a case of MG revealed by thrombosis of the inferior vena cava and of a renal vein in a 40-year-old woman with primary SS, which began with polyarthritis, immune-type lymphadenopathy, and Hashimoto thyroiditis and did not include obvious sicca syndrome. After failure of moderate-dose steroids and then azathioprine, each over separate 9-month periods, the MG responded well within a few weeks to monthly alternation of methylprednisolone and oral cyclophosphamide for 6 months. DISCUSSION: SS may be an underestimated cause of glomerulonephritis, especially membranoproliferative and membranous glomerulonephritis. They should be considered even in the absence of obvious sicca syndrome. Although the prognosis is usually good, renal insufficiency can occur. In cases of MG, if moderate-dose steroids fail, monthly alternation of methylprednisolone and cyclophosphamide for 6 months appears effective and well tolerated, with a low risk of carcinogenicity.
16166103 Th2 cytokine genotypes are associated with a milder form of primary Sjogren's syndrome. 2006 May BACKGROUND: Immunohistological studies on salivary and lacrimal glands have yielded conflicting results on the Th1/Th2 balance in primary Sjögren's syndrome (pSS). OBJECTIVE: To establish whether pSS is a Th1 or Th2 directed autoimmune disease by analysing the polymorphism of the genes encoding for cytokines involved in the regulation of Th1/Th2 differentiation. METHODS: The polymorphisms of the genes encoding for interleukin 4 (IL4) -590 C/T, interleukin 13 (IL13) +2044 G/A, and interferon gamma (IFNG) +874 T/A were analysed in 63 white Finnish patients with pSS (61 female, two male) and in 63 healthy controls. The clinical and immunological data on the pSS patients were analysed in relation to these cytokine gene polymorphisms. RESULTS: There were no significant differences in the genotype or allele frequencies of IL4 -590, IL13 +2044, or IFNG +874 between pSS patients and controls. The erythrocyte sedimentation rate and concentrations of serum IgA and serum beta2 microglobulin were lower in pSS patients carrying the IL4 -590 T allele or the IL13 +2044 A allele than in those not carrying the respective alleles. The IL4 -509 T allele and IL13 +2044 A allele carriers less often had purpura than the corresponding non-carriers. CONCLUSIONS: The frequencies of the cytokine genotypes regulating Th1/Th2 differentiation did not differ between pSS patients and controls. However, the presence of cytokine genotypes with increased susceptibility to atopic and other Th2 diseases was associated with signs of a milder form of pSS. This finding would favour a hypothesis envisaging pSS as primarily a Th1 mediated autoimmune disease.
16142742 Increased acinar damage of salivary glands of patients with Sjögren's syndrome is paralle 2005 Sep OBJECTIVE: Previous findings in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) suggest that increased activity and expression of matrix metalloproteinase 9 (MMP-9) and MMP-3 trigger the destruction of acinar structures in these glands. Tissue inhibitors of matrix metalloproteinases (TIMPs) tightly control MMP activity, and TIMP expression is an important modulator of effects attributed to MMPs. This study was undertaken to investigate the correlation between the balance of MMPs/TIMPs in the LSGs of SS patients and the degree of inflammatory infiltration and acinar structure integrity. METHODS: Three groups of SS patients classified according to focus score and residual tissue were studied. The expression of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 was examined at the messenger RNA and protein levels. The ratio of MMP/TIMP expression (R value) was calculated. Focus score and acinar structure were evaluated by histologic analysis. RESULTS: In SS patients the MMP-3/TIMP-1 ratio was higher than 1 and the MMP-9/TIMP-1 ratio was much higher than 1 whereas the MMP-2/TIMP-2 ratio nearly equaled 1, suggesting elevated proteolytic activity due mainly to MMP-9. R values were independent of the focus score of inflammatory cells, but correlated well with the dramatic changes observed in morphologic integrity of acini, as revealed mainly by the lack of nuclear polarity. Acinar changes were more evident when R values for both MMP-9/TIMP-1 and MMP-3/TIMP-1 were higher. CONCLUSION: This study provides evidence that an altered balance between MMPs and their inhibitors is associated with acinar damage. Since salivary gland acinar cells express both MMPs and TIMPs, these cells may play an important role in extracellular matrix destruction and in the LSG pathophysiology in SS.
15831920 Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relev 2005 May BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.
17112645 Small cell neuroendocrine carcinoma of the sinonasal region. A propose of a case. 2007 Dec We describe a 70-year-old man with rheumatoid arthritis and pulmonary fibrosis who presented with a month's history of pain in the left lateronasal region and inferior eyelid. On examination there was left exophthalmos, difficulty in coordinating eye movements, inflammation, erythema, and pain. Computed tomography showed a 3 cm mass in the left posterior ethmoid region, a biopsy specimen from which showed a small cell neuroendocrine tumour. He refused operation and was treated unsuccessfully with four cycles of cisplatin and etoposide.
17078510 [Adjuvants--essential components of new generation vaccines]. 2006 Adjuvants are essential components of vaccines that augment an immunological reaction of organism. New vaccines based on recombinant proteins and DNA, are more save than traditional vaccines but they are less immunogenic. Therefore, there is an urgent need for the development of new, improved vaccine adjuvants. There are two classes of adjuvants: vaccine delivery systems (e.g. emulsions, microparticles, immune-stimulating complexes ISCOMs, liposomes) and immunostimulatory adjuvants (e.g. lipopolysaccharide, monophosphoryl lipid A, CpG DNA, or muramylpeptides). The discovery of more potent and safer adjuvants may allow to development better prophylactic and therapeutic vaccines against chronic infectious (e.g., HSV, HIV, HCV, HBV, HPV, or Helicobacter pylori) and noninfectious diseases as multiple sclerosis, insulin-dependent diabetes, rheumatoid arthritis, allergy and tumors (e.g., melanoma, breast, or colon cancer).
17060363 Factors masking HMGB1 in human serum and plasma. 2007 Jan High mobility group box 1 protein (HMGB1) is a ubiquitously expressed architectural chromosomal protein. Recently, it has become obvious that HMGB1 can also act as a proinflammatory mediator when actively secreted during cell activation or passively released from necrotic cells. HMGB1 appears to play an important role in the pathogenesis of diseases, including sepsis and rheumatoid arthritis. However, easy, sensitive, and reliable detection systems are required to investigate the clinical significance of HMGB1 in clinical samples for diagnosis and prognosis of diseases. Here, we describe sensitive ELISAs for the detection of HMGB1 in cell culture medium and cell lysates. However, these assays failed to reliably quantitate HMGB1 in serum and plasma when compared with immunoblot analysis. We found that serum/plasma components bind to HMGB1 and interfere with its detection by ELISA systems. In most serum/plasma samples investigated, including those from healthy individuals, we detected IgG antibodies binding to HMGB1. The titers of these antibodies correlated with the capacity of sera to interfere with the detection of recombinant HMGB1 by ELISA. Furthermore, HMGB1 coimmunoprecipitated with several proteins including IgG1, as identified by mass spectrometry. These HMGB1 interacting proteins are currently characterized and may contribute to complex formation, masking, and possibly, modulation of cytokine activity of HMGB1.
17056024 Serum soluble Fas levels in patients with autoimmune rheumatic diseases. 2007 Jan OBJECTIVE: The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases. PATIENTS AND METHODS: We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n=32), rheumatoid arthritis (RA, n=28), Sjögren's syndrome (SS, n=20) systemic sclerosis (SSc, n=21), polymyositis/dermatomyositis (PM/DM, n=15). Patients with osteoarthritis (OA, n=20) and healthy volunteers (n=20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals)+2 SD were considered as elevated. RESULTS: The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found. CONCLUSIONS: The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.
16887405 Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody therapy. 2006 Aug It is well established that anti-tumor necrosis factor-alpha (TNFalpha) antibody is an efficacious disease-modifying drug for rheumatoid arthritis and Crohn's disease. Unfortunately, its long-term use can be associated with ominous pulmonary adverse events, most notably mycobacterial and fungal lung infections. To this end, reactivation of latent tuberculosis infection represents a serious concern of anti-TNFalpha antibody therapy. Given the anticipated increase in the approved indications for these drugs, community-based physicians should be made aware of these events for implementation of better patient selection for anti-TNFalpha antibody therapy and initiation of appropriate measures once these adverse events are observed. This review will address this issue by outlining: 1) the role of TNFalpha in host inflammatory response to injury, particularly during mycobacterial and fungal infections; 2) the salutary effects of anti-TNFalpha antibody therapy in human diseases; and 3) the ominous pulmonary adverse events associated with these drugs.
16887087 [Acute abdomen secondary to spontaneous uterine rupture associated with pyometra]. 2006 Mar A 71-year-old female with rheumatoid arthritis and chronic use of corticosteroids presented to the emergency room with 2 weeks of urinary symptoms, abdominal pain and a mass located in hypo-mesogastrium and both flanks. An X-ray film of the abdomen showed that bowels were displaced by the mass. Laboratory studies showed thrombocytosis (549,000/mm(3)) and leukocytosis (41,800/mm(3)). Several hours after her arrival the patient developed acute abdomen and surgery was indicated. A urinary catheter drained 2100 ml of urine and the abdominal mass was reduced in size but did not disappear. Surgery demonstrated that the urinary bladder covered the fundus and the anterior face of the uterus, where extensive necrosis and a 3-cm perforation were found; 400 ml of foul-smelling pus was drained from the uterine cavity. Due to necrosis, a hysterectomy was performed. The histopathological report indicated necrosis, atrophic cervicitis and endometritis; pus culture developed Escherichia coli and Proteus vulgaris. Despite administration of broad-spectrum antibiotics, the patient developed severe sepsis and died 11 days postoperatively. During a literature review, only one similar case was found. Acute abdomen due to uterine perforation secondary to pyometra and associated with chronic use of corticosteroids is a rare complication.
16857607 Fever of unknown origin in adults: evaluation of 144 cases in a non-university hospital. 2006 The spectrum of diseases found in series of fever of unknown origin shows variation in relation to selection bias; particularly, selection of the most difficult cases in tertiary reference university centres. We present a series of 144 patients presenting to a non-university hospital between 1999 and 2005 (secondary level of the health care system) with a community-acquired fever of unknown origin. In 37 cases (25.7%), the reason for fever could not be explained. Among the 107 patients with a final diagnosis (74.3%), non-infectious inflammatory disorders represented the most prevalent category (35.5%), surpassing infections (30.8%), miscellaneous causes (20.6%) and malignancies (13.5%). 13 entities accounted for over 68% of diagnoses (sinusitis and occult dental infections, Q fever, Epstein-Barr virus and cytomegalovirus infections, lymphoma, colo-rectal adenocarcinoma, adult-onset Still disease, systemic lupus erythematosus, giant cell arteritis and/or polymyalgia rheumatica, rheumatoid arthritis, polyarteritis nodosa, factitious fever and habitual hyperthermia). As demonstrated in other studies, non-infectious inflammatory diseases emerge as the most prevalent diagnostic category. Giant cell arteritis and polymyalgia rheumatica were particularly frequent in the elderly. Epstein-Barr virus and cytomegalovirus infections and habitual hyperthermia were particularly frequent in the youngest patients. There were no major differences in repartition of diagnostic categories between this series and historical university series.
16842190 Novel targets for antiinflammatory and antiarthritic agents. 2006 Inflammation is a complex pathological condition associated with exaggerated human immune system involving various activated immune cells and bio-molecules. Treatment of inflammatory diseases particularly chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease etc. has been a big challenge for scientists as there are no safe drugs available for cure. Current therapeutic approaches to the treatment of inflammatory diseases are centered on cycloxygenase (both COX-1 and 2) proinflammatory enzymes but present available drugs of this category are associated with undesirable gastrointestinal and cardiovascular side effects. Recent scientific advents draw out the secrets of inflammation cache and understanding the involvement of several factors acting as stimulators or inhibitors thus opening new avenues for drug discoveries. Several bio-molecules such as proinflammatory cytokines, components of signal transduction and matrix degrading enzymes resolve inflammatory responses, might be new targets for treatment of chronic inflammatory diseases. This review gathers recent advances in drug research focusing interleukin-1, TNF-alpha, p38 kinase, c-Jun N-terminal kinase MAP kinase, NFkappaB, and matrix metalloproteinases. The biological roles of these inflammatory mediators are clearly understood thus offering new targets for design of novel inhibitors for incurable inflammatory diseases. This also provides an overview of the current nonsteroidal antiinflammatory agents.
16819262 [Relationship between abnormalities of genes involved in DNA damage responses and malignan 2006 Jun The maintenance of genomic stability is an essential cellular function for a variety of well-coordinated regulation of biological activities of organisms, and a failure in its function results in the accumulation of mutations and/or abnormality in the induction of apoptosis, eventually leading to onsets of various diseases, including malignant tumors. DNA damage responses, in particular cell-cycle checkpoint regulation, play important roles in maintaining genomic integrity. In response to DNA damages induced by gamma-irradiation, ultraviolet irradiation, various chemicals, or reactive oxygen species (ROS), intrinsic cell-cycle checkpoint machinery is rapidly activated to arrest cells at particular cell-cycle points, and during cell-cycle checkpoint arrest cells may try to repair damaged DNAs, and then re-start cell-cycle upon the completion of DNA repair. Alternatively, if the extents of DNA damage overwhelm the capacity of the cellular repair machinery, cells may undergo apoptosis to prevent the accumulation of mutations within the organisms. In this article, we will first explain about our current view of DNA damage responses, in particular cell-cycle checkpoint regulation, and summarize our knowledge of the relationships between abnormalities of genes involved in DNA damage responses and malignant tumors, including hematopoietic malignancies. We will also discuss a possible implication of DNA damage responses in autoimmune diseases, such as rheumatoid arthritis.
16819158 The role of Salicornia herbacea in ovariectomy-induced oxidative stress. 2006 Jul Ovarian hormone deficiency increases the generation of reactive oxygen species. Their excess induces oxidative stress, which results in the cell damage or death. It causes the aging diseases-atherosclerosis, rheumatoid arthritis, osteoporosis, etc. Ovariectomized rats are used as oxidative stress models. We verified the effects of ovariectomy-induced oxidative stress on free radical production as evaluated by DPPH elimination, lipoperoxidation evaluated by malondialdehyde levels, and antioxidant activation of superoxide dismutase, catalase, glutathione peroxidase, and estradiol in the liver and sera. Ovariectomized rats were given Salicornia herbacea (SH) intraperitoneally at the dose of 100 mg/kg daily for 2 months. Free radical-scavenging activity of SH was measured in comparison with that of L-ascorbic acid. The histopathology of liver tissue was also investigated. Antioxidative values in the ovariectomized group decreased, but those in the SH-treated group increased due to the free radical-scavenging activity of SH. Moreover, inflammation and cirrhosis in the liver tissue of SH-treated rats decreased significantly. These results suggest that SH may be a potential candidate for an antioxidative reagent.
16817646 Localized pulsed magnetic fields for tendonitis therapy. 2006 Energy medicine has existed for centuries in some parts of the world, but in recent years, western health care practitioners have taken a heightened interest in these therapies. Treatment by use of pulsed magnetic fields (PMF) is currently being explored in both chronic and inflammatory diseases such as cancer, epilepsy, psoriasis, rheumatoid arthritis, and tendinitis. In the U.S., PMFs have already been approved for use in treatment of bone fractures in humans and clinical trials have been conducted for lower back pain. This study presents a summary of the therapeutic potential of a localized PMF treatment for tendinitis using the Softpulse III system. This system has been used to accelerate wound healing and soft tissue swelling. It generates a specific PMF that induces an electrical field within the tendon. This induced electrical field is thought to influence the healing process by affecting the inflammatory cells that line the tendon sheath. In this study, we have used an established model of tendinitis along with a validated method for appraising edema and gait (Achilles' Functional Index), to test the hypothesis that the proposed PMF signal is effective in reducing the indicators of acute tendinitis injury. These experiments were approved by the Institutional Animal Care and Use Committee. Our findings suggest a role for the treatment of soft tissue injury using the Softpulse III therapeutic device. The symbolic stand point of PMF treatments is to push the need for a revolutionary leap, from the more dominant pharmaceutical and surgical interventions, to the advanced applications of non-invasive therapies that would minimize the medicinal risk of side effects, and eliminate the risk of complicated drug interactions.
16805112 The molecular basis of lactose intolerance. 2005 A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.
16789432 Novel N-acyl dehydroalanine derivatives as antioxidants: studies on rat liver lipid peroxi 2006 Apr Oxidative stress has been implicated in the development of many neurodegenerative diseases such as Parkinson and Alzhemier's disease and is also responsible for aging, artherosclerosis, rheumatoid arthritis and carcinogenesis. Olefins such as dehydroalanines have been shown to inactivate free radicals by forming stabilized free radical adducts. Among these molecules N-acyl dehydroalanines react with and scavenge oxygen and hydroxyl radicals. This study describes the synthesis, characterization and in vitro effects on rat liver lipid peroxidation levels, and DPPH free radical scavenging activities of some N-acyl dehydroalanine derivatives. Compounds c, f and j slightly scavenged the level of DPPH radical at 10(-3) M concentration by about 27, 46, and 56%, respectively while compounds a, d, e, f, g, h showed a strong inhibitory effect on lipid peroxidation at 10(-3)M and 10(-4)M concentrations and inhibition was in the range of 76-90%. The possible antioxidant mechanism of the compounds was discussed.
16678033 Serum hyaluronan--a potential marker of cardiac allograft rejection? 2006 May BACKGROUND: The connective tissue component hyaluronan accumulates within the transplanted organ at rejection. Increased tissue content of hyaluronan is seen also in synovial tissue in rheumatoid arthritis and in skin in scleroderma. In these diseases, the elevated hyaluronan levels are reflected by increased concentrations of hyaluronan in serum. The aim of the present study was to study the changes in serum hyaluronan after organ transplantation. METHODS: The experiments were performed in a rat model of heterotopic heart transplantation. Serum hyaluronan was assessed at various times after allogeneic (rejection) and syngeneic (non-rejection) transplantation and correlated with tissue hyaluronan. In addition, serum hyaluronan in animals who had long-term-surviving allogeneic grafts was studied. RESULTS: The hyaluronan concentration in serum was significantly higher in the rejecting than in the non-rejecting group 4 and 6 days after transplantation (p < 0.01). On Day 6, serum hyaluronan had increased by 400% in animals with an allogeneic transplant and by 100% in those with a syngeneic transplant. There was a positive correlation between serum hyaluronan and tissue hyaluronan (p < 0.05). Animals with long-term-surviving grafts displayed normal serum hyaluronan levels. CONCLUSIONS: Rejection of rat heart transplants is associated with strongly increased serum hyaluronan that parallels the hyaluronan accumulation within the transplant.