Stop Lupus Naturally

Natural Lupus Treatment

This book written by Dr. Gary M. Levine discusses the autoimmune disease lupus and just how the writer discovered natural treatments through his own time of hardship. This e-book also features the simple steps regarding how to beat this ailment. With the method that Lupus patients will learn in Natural Lupus Treatment, they will not need pills, injections, and other risky methods to take their lupus away. Patients just need to follow the steps laid out in this system and they can cure their lupus and enjoy a normal life again. Actually there is no cure yet discovered for lupus, however, you will find methods to control and manage its signs and symptoms. The aim of the treatments of lupus generally would be to let the patient experience more comfort and lesser pain. More here...

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Of all books related to the topic, I love reading this e-book because of its well-planned flow of content. Even a beginner like me can easily gain huge amount of knowledge in a short period.

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Mitochondrial Dysfunction in Lupus T Cells

It is presently unclear whether synthesis of GSH or its regeneration from its oxidized form is deficient in lupus patients. GSH is also required for interleukin-2-dependent T-cell proliferation (45) as well as CD2- and CD3-mediated T-cell activation (46). Thus, a low GSH content may also inhibit CD3-induced H2O2 production. Nevertheless, GSH deficiency predisposes cells for ROI-induced cell death (14,24,47). Diminished H2O2-induced apoptosis of cells with low baseline GSH levels indicates a severe dysfunction of redox signaling in patients with SLE. Increased ROI production may lead to skewed expression of redox-sensitive surface receptors and lymphokines. As examples, ROIs regulate gene transcription and release of TNF-a and IL-10 (48), both of which are elevated in sera (49,50) and freshly isolated PBLs of patients with SLE (51,52). Expression of TCR -chain is sensitive to oxidative stress (53), and thus increased ROI levels may explain, at least in part, low TCR -chain expression...

Lupus Prone Mice With Defined Mutations

(Canale-Smith syndrome 239-241), CD95 ligand (242), and caspase-10 (243). These syndromes share in common the development of severe lymphadenopa-thy because of CD3+CD4CD8- T cells and the high incidence of often lupuslike autoimmune disease. CD95 defects alone generally do not convey autoimmunity per se, but rather accelerate and amplify any underlying autoimmune diathesis For example, C57BL 6-lpr animals develop mild inflammatory disease consisting of lymphadenopathy, anti-single-stranded DNA (anti-ssDNA) antibodies, and mild, if any, glomerular disease MRL Mp-lpr animals develop widespread inflammation, including lymphadenopathy, autoantibodies of multiple specificities including anti-dsDNA, antiribonucleoprotein, anticardiolipin, and antiribosomal P, immune complex glomerulonephritis, as well as sialadenitis and hepatitis (see Subheading 1.2. 155-157). Thus, these mutations have often been used in murine lupus to accelerate the in vivo assay. Several other mutant animal models have...

Conclusions The Selection of Murine Lupus Models

The diverse array of inbred and genetically altered mice provides many models for systemic lupus erythematosus, each with particular clinical manifestations and unique pathogenesis (Tables 1-4). Investigators should therefore choose models based on areas or phenomena of interest within the lupus autoimmune spectrum For instance, studies focusing on anti-dsDNA antibody responses, T-cell autoreactivity, or hemolytic anemia may find the best supporting literature and precedence in the NZ systems. In contrast, studies of diversification and diversity of autoantibody repertoires and multisystem autoimmune disease may prefer MRL models. Congenic autoimmune-prone CD95-mutant animals, like MRL Mp-lpr lpr, may provide particularly rapid assay systems, but investigators should beware of possible confounding from the concomitant, severe lymphadenopathic process. Finally, studies with interests Targeted Genes With Lupus-Like Phenotypes in some specific genes might benefit from the lupuslike...

Diagnosis of Murine Lupus

At present, there is no consensus as to the diagnosis of lupus in murine models, but in general, most studies judge experimental interventions based on the presence of antinuclear antibodies, including anti-dsDNA, and immune-deposit-related glomerulonephritis. Thus, minimal analysis includes assessment of the fluorescent antinuclear antibody test and anti-dsDNA antibodies and histo-pathological analysis of kidneys, often including immunofluorescence for IgG. The assessment of other organs, such as salivary glands or joints, has not been broadly studied or codified. In some investigations, serial analysis has been performed for antinuclear antibodies and or specific autoantibodies (Subheading 3.2.), serum creatinine and urea nitrogen, urine proteinuria (Subheading 3.3.), and even kidney biopsies (249) unfortunately, such use remains nonstandardized, and the predictive value of any of these tests is incompletely known (250). Consequently, most experiments are performed as...

Mitochondrial Hyperpolarization and ATP Depletion Predispose Lupus T Cells to Necrosis

In response to treatment with exogenous H2O2, a precursor, or ROI, lupus T cells failed to undergo apoptosis, and cell death preferentially occurred via necrosis. As noted in ref. 24, H2O2 triggered a rapid increase of AWm and ROI production, which was followed by apoptosis of PBLs in healthy subjects. By contrast, H2O2 failed to elevate AWm, ROI production, and apoptosis, but rather elicited necrosis in patients with lupus. Both CD3 CD28-induced H2O2 production and H2O2-induced apoptosis require mitochondrial ROI production. Therefore, diminished CD3 CD28-induced H2O2 production and H2O2-induced apoptosis together with deficient elevation of AWm and ROI levels reveal deviations of key biochemical checkpoints in mitochondria of patients with SLE.

Lupus panniculitis

Tcell And Cell Sle

Patients with lupus erythematosus may rarely present with prominent involvement of the subcutaneous tissues, a condition that has been termed lupus panniculitis or lupus profundus. Lupus panniculitis reveals subcutaneous plaques and indurations, mostly located on the extremities, which can simulate clinically and histopathologically those observed in subcutaneous T-cell lymphoma (see Chapter 5) (Fig. 20.20) 57 . Antinuclear antibodies and other criteria for the diagnosis of systemic lupus erythematosus may be absent in some cases. Histology shows a predominantly lobular pan-niculitis, often with concomitant presence of broadened fibrotic septa. A useful feature for the differentiation of subcutaneous T-cell lymphoma from lupus panniculitis is the presence in the former of so-called 'rimming' of fat cells by pleomorphic atypical T lymphocytes that are positive for proliferation markers. It must be remembered that rimming of fat lobuli by lymphocytes is not a diagnostic feature per se,...

Swapan K Nath Jennifer A Kelly John B Harley and R Hal Scofield Summary

Systemic lupus erythematosus (SLE) is a prototype systemic, autoimmune inflammatory disease that can involve virtually any organ or tissue type. The disease has a strong familial tendency but, like most human illness, has a complex pattern of inheritance that is consistent with multiple susceptibility genes as well as environmental risk factors. Association studies have been performed, especially for the major histocompatibility complex on chromosome 6 and for various complement components. Several large familial studies have begun to report results for genetic linkage. Linkage has been established for many genetic intervals. SLE is a complex clinical illness, and investigation of the genetics of the illness based on clinical manifestations revealed linkages not found without consideration of the phenotype of the disease. Key Words Autoantibodies autoantigens complement genetic association genetic linkage HLA systemic lupus erythematosus

Discussion and Future Directions

Convincing Linkage Results Published (Exceeding Lander-Kruglyak Significance and or Our Ad Hoc Criteria) With Lupus From Oklahoma Pedigree Collection Based on Pedigree Stratification Strategy Convincing Linkage Results Published (Exceeding Lander-Kruglyak Significance and or Our Ad Hoc Criteria) With Lupus From Oklahoma Pedigree Collection Based on Pedigree Stratification Strategy

Pharmacological Targeting of Mitochondrial Dysfunction in SLE

Mitochondrial hyperpolarization predisposes for increased ROI production (38). Oxidative stress affects the activity of transcription factors activation protein (AP-1) and NF-kB (64,65) and, further downstream, may lead to the skewed expression of IL-2, TNF, and IL-10 (48). Increased spontaneous apoptosis of lymphocytes has been linked to increased IL-10 production, release of Fas ligand, and overexpression of Fas receptor in SLE (61). Because increased ROI levels confer sensitivity to H2O2-, NO-, TNF-, and Fas-induced cell death (14,15), elevated baseline AWm, ROI production, and intracellular pH may have key roles in altered activation and death of lupus T cells. Although mitochondrial hyperpolarization was not affected, IL-10 antibody or IL-12 normalized ROI production and intracellular alkalinization in lupus PBLs (37). Therefore, IL-10 antagonists may partially correct signaling dysfunction in lupus. A proapoptotic 1,4-benzodiazepine (Bz-423) has been found to promote...

Measurement of Cytokines in Autoimmune Disease

The immune system alterations that characterize systemic autoimmune diseases, with systemic lupus erythematosus (SLE) the prototype, extend to virtually all components of the innate and adaptive immune responses. A current paradigm suggests that a host microenvironment that favors maturation of antigen-presenting cells can promote activation of autoantigen-specific lymphocytes and result in chronic immune system activation and tissue damage (1-3). This scenario involves dendritic cells, T cells, and B cells, as well as the products of inflammatory cells of the innate immune system, including monocytes and neutrophils. The effector functions implemented by these immune system cells are induced and mediated by cytokines, along with autoantibodies and products of the complement system. SLE is characterized by production of autoantibodies, and abundant data indicate that those autoantibodies are both antigen driven and depend on T-cell help. The T-cell-derived signals that drive B-cell...

Stanford L Peng Summary

Murine models of systemic lupus erythematosus provide fertile research systems for the pathogenesis and therapy of systemic autoimmune disease. Their phenotypes span the broad range of clinical manifestations of human lupus and consist of both spontaneous and experimentally induced disease in both inbred and targeted mutant animals. This chapter contrasts the clinical characteristics of these various models, providing an outline for the use and analysis of these in vivo autoimmune systems. Keywords Arthritis autoantibodies autoimmune diseases glomerulonephritis hemolytic anemia lupus inbred mice knockout mice mutant mice transgenic mice.

Murphys Recombinant LargeMpJ

Of the available lupus-prone strains, MRL Mp and their congenic MRL Mp-lpr lpr strains develop the most systemic and severe form of autoimmunity, involving multiple autoantibody specificities, such as anti-dsDNA, ribo-nucleoprotein (including small nuclear ribonucleoproteins snRNPs , Ro, La, Su), ribosomal, and erythrocyte, as well as rheumatoid factor and cryoglobulins. End-organ disease includes not only varying and severe forms of glomerulonephritis, but also sialoadenitis in about 90-95 and inflammatory arthritis in about 75 , as well as less-often described but often seen inflammatory lesions of the liver, eyes, blood vessels, reproductive organs, and nervous system (7,101,103,104). 1.2.3. Use in the Study of Lupus Pathogenesis

Experimentally Induced Models

Few widely used, experimentally induced models exist for lupus. Graft-vs-host disease models have been sometimes studied because of the concomitant development of lupuslike autoimmunity however, given the importance of allogeneity, its physiology probably represents a mode of pathogenesis distinct from the other lupus models described here (194) (see also Chapter 14). Alternatively, when exposed to bacillus Calmette-Guerin, nonobese diabetic mice have been demonstrated to develop hemolytic anemia, autoantibodies, worsened sialadenitis, and immune complex-mediated glomerulonephritis (195), but The aliphatic hydrocarbon pristane (2,6,10,14-tetramethyl-pentadecane) has long been known to induce plasmacytomas (196-199) and arthritis (200-204) in susceptible BALB c mice. Relatively recently, it was found to induce, in several strains, many different serological autoimmune phenomena, including anti-DNA and antiribonucleoprotein antibodies and glomerulonephritis (205208), through mechanisms...

Application of Linkage to SLE

Thrombocytopenia And Genetic

The strategy of using pedigree stratification as a way to discover linkage effects has only been pursued by our Oklahoma group. We have taken the advantage of a pedigree stratification strategy from our huge collection of pedigrees with relevant clinical and medical information available for each individual, especially for the patients with SLE. Therefore, the extraordinary clinical heterogeneity in lupus is consistent with this phenotype as a treasure trove of genetic linkages based on stratifying pedigrees by clinical or demographic features. The rationale behind the subgrouping of the SLE families with a common clinical feature is to make the SLE families more genetically homogeneous. It was anticipated that, regardless of the actual number of genes involved in SLE, decreasing sample heterogeneity by subgrouping families based on race and common associated traits would increase the likelihood of identifying genes for SLE. Although this approach has many advantages, the major...

Summary

Abnormal expression of key signaling molecules and defective functions of T lymphocytes play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). T-cell receptor (TCR) CD3-mediated stimulation of SLE T cells shows increased protein tyrosine phos-phorylation of cellular proteins, with faster kinetics, heightened calcium response, and decreased interleukin (IL)-2 production. The molecular mechanism of T-cell signaling abnormalities in SLE T cells is complex and cannot be explained fully by the current theories of T-cell signaling. Current research on lymphocyte signaling abnormalities in SLE has been directed toward investigating various factors that contribute to abnormal tyrosine phosphorylation, intracellular calcium response, and cytokine production. Latest developments suggest multiple components, including altered receptor structure, supramolecular assembly, modulation of membrane clustering, aberrant cellular distribution, and precompartmentalization with...

Edited by

TCR -Chain Abnormalities in Human Systemic Lupus Erythematosus A growing number of studies have revealed that the expression of many genes is abnormal in T lymphocytes of patients with systemic lupus erythematosus (SLE). Although aberrant expression of signaling molecules may arise intrinsically or in response to the environment, these abnormalities play a significant role in the pathogenesis of this autoimmune disease. Modern research on lymphocyte signaling abnormalities in SLE has been directed toward identifying defective expression of various signaling molecules, understanding the molecular basis of the deficiency, and dissecting the T-cell signaling abnormalities that result from abnormal gene expression. The developments suggest that interplay of abnormal transcriptional factor, aberrant messenger RNA processing editing, ubiquitination, proteolysis, oxidative stress, and changes in chromatin structure invariably contribute to the abnormal expression of numerous signaling...

New Zealand Strains

The most well-described New Zealand (NZ) lupus strains include the NZ black (NZB) x NZ white (NZW) F1 and NZ mixed (NZM). Their initial origins are somewhat obscure, but NZB appears to have originated in the late 1940s during inbreeding of outbred stocks at the University of Otago School of Medical Sciences, New Zealand, during efforts to develop mouse strains for cancer research (17-19), and NZW was derived separately in 1952 during selective Histopathology of Lupus-Prone Mice Histopathology of Lupus-Prone Mice 1.1.3. Use in the Study of Lupus Pathogenesis

BXSB Animals

Like NZ animals, disease in BXSB consists predominantly of anti-DNA antibodies and glomerulonephritis antierythrocyte antibodies have been described, but are not well characterized. Unlike other lupus models, however, BXSB develops a male-predominant disease because of the Y-linked autoimmune accelerator (Yaa see refs. 158 and 159), inherited from the SB Le parental strain (160), which is solely responsible for conferring disease to susceptible strains (161,162). 1.3.3. Use in the Study of Lupus Pathogenesis Although less well studied than NZ or MRL mice, BXSB animals have also been used in studies of lupus genetics (163-166), and for studies of the T-cell-dependent development of pathogenic anti-DNA antibodies (105,167,168). The roles of some cell lineages, cytokines, and costimulatory molecules have been investigated (169-172), and some transgenic studies have implicated the impor tance of abnormalities of antigen presentation (45,173). Like other lupus models, BXSB animals are...

Indications for aPL Testing

A recent study has suggested that aPL may appear many years prior to the diagnosis of an autoimmune connective tissue disease such as lupus, and aPL-positive patients appeared to be at risk of more severe lupus later in the disease course, suggesting that immune dysregulation leading to autoanti-body production may precede the appearance of symptoms by many years. Amengual O, Atsumi T, Khamashta MA, Koike T, Hughes GRV (1996) Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome. Br J Rheumatol 35(12) 1239-1243 Bertolaccini ML, Hughes GR (2006) Antiphospholipid antibody testing which are most useful for diagnosis Rheum Dis Clin North Am 32(3) 455-463 Bertolaccini ML, Sanna G, Ralhan S, Gennari LC, Merrill JT, Khamashta MA et al (2003) Antibodies directed to protein S in patients with systemic lupus erythematosus prevalence and clinical significance. Thromb Haemost 90(4) 636-641 Bertolaccini ML, Hughes GR, Khamashta MA (2004) Revisiting...

Who gets osteoporosis

Children, adolescents, and young adults can get osteoporosis too, particularly those with genetic or nutritional disorders, and eating disorders such as anorexia nervosa and bulimia, because they do not make hormones or absorb calcium, Vitamin D, and other nutrients and protein required for normal bone development. Those who are treated with medications that interfere with bone development may also get osteoporosis. People who are treated with long-term methotrexate (> 1 month), usually for cancer or arthritis, are more at risk. Long-term use of the gonadotropin-releasing hormone analogs, such as Lupron, for the treatment of endometriosis in young women can contribute to the development of osteoporosis as well. And the most common class of medication to cause osteoporosis or osteopenia at any age is corticosteroids, used for such problems as lupus, arthritis, or asthma. Osteoporosis occurring after taking a glucocorticoid is so common that it has its own name glucocorticoid-induced...

B cells and antibodymediated immune responses in chronic neuroinflammation

A genuine autoimmune humoral response, as in the (NZB x NZW) F1 murine model for systemic lupus erythematodes (SLE), presents with stable and persistent autoantibodies in the serum as a hallmark of its pathology. These serum autoantibodies presumably derive from long-lived plasma cells in the bone marrow and are characteristically present already before onset of the disease (Hoyer et al., 2004). This is not the case for classic MS (Antel and Bar-Or, 2006), but some of these traits can be found in another type of chronic neuroinflammation called neuromyelitis optica (NMO, also Devic's syndrome), a demyelinating CNS disease with distinct clinical, therapeutic, and histopathologic features compared to MS. CNS infiltrates in NMO are marked by extensive eosinophil infiltration, complement activation, and necrotizing demyelination with prominent vascular hyalinization (Lucchinetti et al., 2002). Recent serological studies have identified a serum autoantibody called NMO-IgG, which binds to...

Mortality Morbidity and Damage Associated with aPL

There is an increasing evidence that thrombosis contributes to irreversible organ damage as well as mortality in lupus patients with aPL. Ruiz-Irastorza G, Egurbide MV, Ugalde J, Aguirre C (2004) High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med 164(1) 77-82 Shah NM, Khamashta MA, Atsumi T, Hughes GRV (1998) Outcome of patients with anticardiolipin antibodies a 10 year follow-up of 52 patients. Lupus 7(1) 3-6

Clinical features

Patients are adults of both sexes 1,2,44 . Reports in children exist but phenotypical data in some cases are incomplete 45,46 . A long history of 'benign panniculitis' is often present 22 . Clinically, patients present with solitary or multiple erythematous tumours or plaques, which are usually not ulcerated and are located most commonly on the extremities, especially the lower ones (Figs 5.1 & 5.2) 1,2,44 . Other sites of the body, including the head, may be affected (Fig. 5.3) 22,47 . Skin lesions are non-specific and may simulate erythema nodosum, lupus panniculitis or other panniculitic diseases. One patient with alopecic lesions on the scalp has also been described 48 . Spontaneous resolution of some of the

Bcells in autoimmuneinflammatory disease

Autoimmune and inflammatory diseases remain an area of significant unmet medical need. B-cells are critical regulators of immune responses and are implicated in the pathogenesis of conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and immune thrombocytic purpura (ITP) 1-4 . Principal among

Clinical Box 21 Graft Versus Host Disease

A main reason for the shortage of transplant organs is the fact that the tissues of the donor and the recipient need to match for successful transplantation. Tissues are matched when they have a similar pattern of cell surface proteins. Cell surface proteins are in fact glycoproteins due to the carbohydrates (sugars) attached to their surface. The carbohydrate acts as a flag designating the cell as belonging to the individual. The cellular gly-coprotein pattern may specify an individual within a species or specify a species. If a particular sugar is missing from the surface of a cell, the immune system may recognize this cell as foreign and try to kill it. An attack on self tissue may lead to autoimmune diseases, where the autoimmune reaction can be directed against a specific tissue such as the brain in multiple sclerosis or the digestive tube in Crohn disease. In other cases, the overly active immune system may attack many cells and tissues so that various organs are affected such...

Key advances in preclinical validation

Studies of pre-clinical models of other autoimmune diseases have also been reported recently. In a model of systemic lupus erythematosus, CCR2_ _ mice exhibited prolonged survival and reduced renal disease relative to their WT counterparts 20 . Importantly, reduced macrophage and T-cell accumulation in the renal lesion sites was noted. Overall, these data are consistent with other recent studies on genetic deletion of MCP-1 21 or administration of a peptide antagonist of CCR2 22 in models of lupus. The recent data with experimental autoimmune encephalomyelitis (EAE, a rodent model of human multiple sclerosis) are more complex, in that different outcomes were observed depending on the system studied. Administration of a small molecule antagonist blunted EAE disease progression in C57BL 6 mice 15 . Likewise, genetic deletion of CCR2 in the C57BL 6 background also reduced EAE disease score, particularly in the early stages of disease 23 . However, CCR2_ _ mice on a Balb C background...

New diagnostic approaches

To identify the gene expression signatures induced by various pathogens, Chaussabel et al. examined peripheral blood mononuclear cells (PBMCs) obtained from pediatric patients presenting with various illnesses (2005). Specifically, they examined diseases with distinct immunological components such as systemic lupus erythematosus (SLE), influenza A, Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae. They also examined adult patients who received liver transplants with immuno-suppressive therapy or patients who received bone marrow transplants

Structural features of the TLRs

Since the discovery of the TLRs, a number of exogenous and endogenous ligands have been reported for each of the receptors 25 . Other work done over the past 15 years has focused on the effects of stimulating or ablating TLR signaling in models of disease. Agonists were investigated long before the receptors were known, and this work continues with efforts to use TLR ligands as vaccine adjuvants, as prophylactics against pathogen exposure in the area of biodefense 26 , or as immunostimulators alone or with other drugs 4 , particularly in oncology. Most recently, there is an appreciation that TLRs also respond to endogenous ligands, as in the case of TLR7 and TLR9 activation by autologous single-stranded (ss) RNA (TLR7) and DNA (TLR9) in systemic lupus erythematosus (SLE) 27 . This raises the possibility that antagonists to these two TLRs could be used for this indication. The complex signaling pathways downstream of TLRs have also been investigated and some essential components have...

Therapeutic significance

Numerous studies have demonstrated that FTY720 synergizes with classical immunosuppressants (e.g. cyclosporine A, FK506, RAD001, steroids) in rodent and non-human primate models of solid organ and islet transplantation 24,25,37,42 . The most profound activity of FTY720 monotherapy has been seen in experimental autoimmune encephalomyelitis (EAE) 24,31,43 . Efficacy has also been reported in models of systemic lupus erythematosus, graft versus host disease, type-1 diabetic mice, adjuvant- and collagen-induced arthritis, experimental autoimmune myocarditis, colitis, experimental autoimmune thyroiditis and uveoretinitis 24,25,44-51 .

Fas Mutations and Various Disorders in Experimental Animals and Humans

Soon after the reports of Fas gene mutations in lpr and lprcg experimental mice, several studies identified function-ablating mutations of the Fas gene in patients with a human congenital lupus-like syndrome, designated autoimmune lympho-proliferative syndrome (ALPS) or Canale-Smith syndrome (CSS), which produces symptoms similar to the lpr mouse phenotype. As shown in Table 1, at least 29 distinct Fas gene mutations have been reported in patients with congenital ALPS or CSS disorders. These germline mutations are concentrated in exon 9, which forms the death domain of Fas proteins, and consist mainly of point mutations causing premature termination or missense mutations. More interestingly, it is instructive that some patients with ALPS or CSS develop a lymphoid neoplasm, malignant lymphoma, during their lives. This has encouraged many researchers to study tumor biology related to defective Fas-mediated apoptosis in acquired incurable disorders. In fact, acquired malignancies have...

Further Clinical Opportunities For Hdac Inhibitors

In addition to polyglutamine-induced neurodegeneration, HDAC inhibitors may find application in immunological disorders. Cytokine production is regulated through selective patterns of histone acetylation 69 . The HDAC inhibitor SAHA exhibits anti-inflammatory properties both in vitro and in vivo 70,71 . In a model of lipopolysaccharide induced inflammatory response in mice, SAHA decreases the levels of circulating pro-inflammatory cytokines, such as TNF-a, IL-1-b, IL-6 and IFN-g. Recently, TSA and SAHA have also been shown to antagonize systemic lupus erythematosus in a mouse model 72,73 .

Lips and Perioral Skin

Contact dermatitis of the lips includes lipstick dermatitis, caused by any of several ingredients, topical and dental medications, objects habitually chewed (e.g., metal or plastic in pens and pencils or rubber in pencil erasers) musical instruments (e.g., reeds or wooden instruments, such as recorders or flutes) flavors, or dental braces (which can also be a source of irritation directly or from drooling). Other conditions to be considered include candidal cheilitis, cheilitis glandularis, cheilitis granulomatosia, lichen planus, lupus erythemtosus, and actinic cheilitis, to name a few.

Acquired partial lipodystrophy

Also known as Barraquer-Simmons syndrome, more than 250 patients with acquired partial lipodystrophy (APL) have been reported in the literature (46). APL is characterized by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in a cephalocaudal sequence, sparing the lower extremities. Often, excess fat accumulation is seen over the lower abdomen, gluteal region, thighs, and calves. The onset of fat loss usually occurs during childhood or adolescence, at a median age of 7 yr, whereas the excess fat accumulation is noted to occur at the onset of puberty or with weight gain and glucocorticoid therapy. Fat loss occurs in a gradual process over a period of few months up to 2 yr, and 75 of patients have discernible fat loss before 13 yr of age. Women are reportedly affected four times more often than men (46). Whole-body MRI studies in affected patients confirmed the loss of subcutaneous fat from face, neck,...

Now that I have been diagnosed with MS how do I learn to cope with this disease

System lupus erythematosus (SLE) The first step in dealing with MS is acceptance of the diagnosis (i.e., what does the diagnosis mean ). A diagnosis may be easy for the neurologist, but the affected person may not react positively or may even be suspicious about the seeming ease of establishing the diagnosis. Obviously, the confidence in the physician is a prerequisite in accepting the diagnosis. Although physicians other than neurologists may suspect the diagnosis, the diagnosis of MS must be made by a neurologist. It is also assumed that appropriate clinical neurologic examinations and tests such as MRIs of the brain and spinal cord, cerebrospinal fluid (CSF) examination, and certain blood work will be performed and the results reviewed. These tests are usually needed to eliminate other diseases. Illnesses that can sometimes mimic MS, such as syphilis, system lupus erythematosus (SLE) , and vitamin B12 deficiency, must be eliminated from consideration. Occasionally, patients will...

Obstetric Manifestations

The strongest relationship between aPL and fetal losses has been found after 14 weeks. Lupus anticoagulant (LA) has shown the strongest association with recurrent fetal losses before 24 weeks' gestation, although it has not been possible to analyze the association of LA with early miscarriages (< 13weeks). aCLs are also related with recurrent losses before 24 weeks. IgG aCL is the only one that has been associated with early miscarriages.

Microarray Studies from Blood

And found that the MS patients had expression profiles indicating anti-apoptosis and autoreactive T-cell activation states. Achiron et al. 3 used a 12,000-gene array to compare the gene expression patterns in PBMCs between 26 relapsing-remitting MS patients and 18 healthy controls. Identified differentially expressed genes were also involved in T cell activation and expansion, inflammation, and anti-apoptotic mechanisms. In another study by the same group, Mandel et al. 79 compared the PBMC gene expression profiles of 13 RRMS patients, five systemic lupus erythematosus (SLE) patients, and 18 healthy controls, followed by verification of differentially expressed genes by RT-PCR and ELISA in 15 RRMS patients, eight SLE patients, and ten healthy controls. As in the Maas et al. 77 study (which also included SLE), the MS and SLE patients had a similar gene expression pattern that distinguished them from the healthy controls but also had expression profiles that distinguished the two...

Methodology to Detect EMP

A different approach to measuring EC damage has been circulating ECs (CECs). CECs have been described in patients with cardiovascular disease namely, in myocardial infarction 72 , in unstable angina 73, 74 , and postangioplasty 75 . In addition, CECs have also been found to be elevated in Rickettsia Conorii infection 76 and hematological disorders such as sickle cell disease 77, 78 , TTP 79 , and systemic lupus erythematosus (SLE) 80 .

Acquired thrombophilia

The antiphospholipid syndrome is the most common cause of acquired thrombo-philia. Identified autoantibodies include lupus anticoagulant and anticardiolipin antibodies. However, there is some evidence that other as yet unidentified auto-antibodies may cause thrombosis and fetal loss in pregnancy. The lupus anticoagulant is so called because it causes a prolongation of the activated partial thromboplastin time even when diluted (because the autoantibody Of women with recurrent miscarriage (three or more), 15 have persistently positive results for phospholipid antibodies. If untreated, 90 will have spontaneous abortions or stillbirths in subsequent pregnancies. It is possible that lupus anticoagulant (30 of cases) and anticardiolipin antibodies (70 of cases) are the same autoantibody identified in different assays. Clinical features of the antiphospholipid syndrome are recurrent fetal loss, thrombosis (arterial and venous), thrombocytopenia, haemolytic anaemia, hypertension, pulmonary...

Pathogenesis of Paraneoplastic Nervous System Syndromes

Antibodies directed to antigens that are components of cell surface receptors are often pathogenic in vivo (such as ion channel antibodies and, possibly, mGluR1 antibodies) 95, 182, 183 . The pathogenic relevance of antibodies to intracellular targets is much more controversial, but antinuclear antibodies are reported to be pathogenic in some diseases such as systemic lupus erythematosus 184 .

Proteincoated artificial cells in immunoadsorption

Albumin can bind tightly to the ultrathin collodion membrane of adsorbent artificial cells, and was initially used to increase the blood compatibility of the adsorbent artificial cells for hemoperfusion (Chang, 1969a). This albumin coating has also been applied to synthetic immunosorbents, resulting in blood compatible synthetic blood group immunosorbents (Chang, 1980d). The albumin-coated synthetic adsorbent has been applied clinically for removing blood group antibodies from plasma for bone marrow transplantation (Bensinger et al., 1981). In addition, albumin-coated collodion activated charcoal (ACAC) was found to effectively remove antibodies to albumin in animal studies (Terman et al., 1977). This principle has become a basis of one line of research in which other types of antigens or antibodies are applied to the collodion coating of the activated charcoal to form immunosorbents. Other immonosorbents based on the same principle have also been developed for the treatment of human...

APL and Transplantation

And renal transplantation a risk assessment. Lupus 12(7) 555-559 Wagenknecht DR, Becker DG, LeFor WM, McIntyre JA (1999) Antiphospholipid antibodies are a risk factor for early renal allograft failure. Transplantation 68(2) 241-246 Wagenknecht DR, Fastenau DR, Torry RJ, Becker DG, LeFor WM, Carter CB et al (2000) Risk of early renal allograft failure is increased for patients with antiphospholipid antibodies. Transpl Int 13(Suppl 1) S78-S81

Are there any medications that I should adjust or stop taking while Im being treated for osteoporosis

I have been taking steroids for the treatment of my lupus. Is there any way that I can reduce the dosage so that the steroids do not further weaken my bones Systemic lupus erythematosis (SLE or lupus for short) and other inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel diseases, and asthma, are often treated with steroids for long periods of time, but it does not take long for steroids to weaken bones. In fact, significant bone loss can occur with > 7.5mg daily in as little as 3 months. Courses of treatment for longer than 6 months give you a 50 chance of developing osteoporosis. So, in terms of your bones, it is critical to find ways to reduce your dosage of steroids or to begin medications such as a bisphosphonate and, if appropriate, estrogen therapies, that will help prevent further bone loss. While you may not be able to lower your dose of steroids if your lupus is well controlled on your current dose, you likely can add medications that may make your...

Protein coated artificial cells in immunoadsorption

Albumin can bind tightly to the ultrathin collodion membrane of adsorbent artificial cells (Chang, 1969a). This was initially used to increase the blood compatibility of the adsorbent artificial cells for hemoperfusion (Chang, 1969a). We also applied this albumin coating to synthetic immunosorbents resulting in blood compatible synthetic blood group immunosorbents (Chang, 1980d).This albumin-coated synthetic adsorbent has been applied clinically for removing blood group antibodies from plasma for bone marrow transplantation (Bensinger et al., 1981). In addition, albumin-coated collodion activated charcoal (ACAC) was found to effectively remove antibodies to albumin in animal studies (Terman et al., 1977). This has become the basis of one line of research in which other types of antigens or antibodies are applied to the collodion coating of the activated charcoal to form immunosorbents. Other immonosorbents based on this principle have also been developed for the treatment of human...

Specific Causes Of Obscure Lower Gi Bleeding Vascular Diseases

Systemic vasculitis (polyarteritis nodosa, systemic lupus erythe-matosis, dermatomyositis, Henoch-Schonlein purpura) may affect multiple organs, including the GI tract (30-32). The most common presentation with GI involvement is ischemic bowel disease and perforation, but significant bleeding occurs in some cases. Colonoscopy in these patients may detect multiple petechial or ecchymotic lesions, and biopsies are compatible with evidence of vasculitis.

Surface Properties of Artificial Cell Membranes

Albumin can bind tightly to the ultrathin collodion membrane of adsorbent artificial cells. This is initially used to increase the blood compatibility of the adsorbent artificial cells for hemoperfusion (Chang, 1969a). This albumin coating has also been applied to synthetic immunosorbents, resulting in blood compatible synthetic blood group immunosorbents (Chang, 1980d). In addition, Terman etal. (1977) showed in animal studies that albumin-coated collodion activated charcoal (ACAC) can remove antibodies to albumin. This has become a basis of one line of his research in which other types of antigens or antibodies are applied to the collodion coating of the artificial cells to form immunosorbents. Other immunosorbents based on this principle have also been developed for the treatment of human systemic lupus erythematosus removal of antiHLA antibodies in transplant candidates treatment of familial hypercholesterolemia with monoclonal antibodies to low-density lipoproteins (Terman, 1980

Role of Lselectin in disease

In addition to cell-surface adhesion molecules, the soluble forms of these molecules have been receiving an increasing amount of attention. While soluble adhesion molecules have been used successfully as markers of inflammation or disease activity, their role in physiological processes must also be considered (reviewed in 252 ). Specifically, significantly increased levels of sL-selectin have been reported to be associated with a number of different disease conditions including chronic myeloid and lymphocytic leukemia 253-255 , sepsis 19, 256 , HIV infection 19 , atopic dermatitis 257 , psoriasis 258 , and lupus 259 . As discussed above, since sL-selectin retains functional activity, these increased levels may have important physiological effects on leukocyte migration in these patients. In fact, higher levels of sL-selectin in acute myeloid leukemia patients at the time of diagnosis correlated with decreased probability of achieving complete remission, shorter event-free survival,...

Signaling Milieus At The Effector Sites

Treated with prolactin for four weeks, they develop a lupus-like syndrome, with elevated anti-DNA titers, increased numbers of anti-DNA B cells, and an overall shift of B cells from the transitional compartment to the follicular and marginal zone compartments (103). Therefore, it appears that interactions between prolactin and TGF- take different forms to support mucosal immune function in different tissues.

Conclusions and future challenges

Despite over 20 years of research, much about the regulation and function of L-selectin remains unknown. For example, while many different ligands that can be recognized by L-selectin have been described, definitive evidence demonstrating any of these molecules to be the physiological ligand for L-selectin is lacking. Furthermore, the PSGL-1-independent L-selectin ligands expressed by leukocytes remain to be identified. Important to L-selectin function is the generation of transmembrane signals through L-selectin following ligation. These signals, described following binding of ligands and L-selectin-specific mAbs, result in increased leukocyte effector functions such as enhancement in leukocyte binding activity and subsequent chemotaxis. However, it is unclear how such a short cytoplasmic tail, lacking known binding domains for signaling molecules, mediates such a variety of functions. Much of the differences observed in the migration of lymphocyte subsets can be explained by...

Lymphocytic infiltration of the skin

Lymphocytic infiltration of the skin (Jessner-Kanof) can be confused histopathologically with lesions of B-cell chronic lymphocytic leukaemia (B-CLL). The coexpression of CD20, CD5 and CD43 on the B cells of B-CLL as well as the detection of a monoclonal rearrangement of the JH gene, in contrast to the predominance of polyclonal T lymphocytes in lymphocytic infiltration of the skin, help to distinguish these diseases. It has been recently proposed that lymphocytic infiltration of the skin and lupus erythematosus tumidus represent one and the same disease 95 .

Irreversible inhibitors

Bmx Inhibitors

Flux (IC50 40 nM), but also inhibits Ca flux in T-cells (IC50 466 nM). Since Btk is not expressed in T-cells, this data suggests functionally relevant off-target activity. Acrylamide 1 was efficacious at 3 mg kg in murine passive transfer CIA and MRL lpr lupus models. Not surprisingly, 1 has potent activity (0.1-11 nM) against other kinases containing a cysteine analogous to Btk Cys481, including Blk, Bmx, epidermal growth factor receptor (EGFR), Itk, and Janus kinase 3 (JAK3) 42 . Compound 1 is subject to glutathione conjugation, and analogs with increased substitution on the electrophilic double bond have reduced

Isoelectric Focusing of the CSF

Polyspecific Response Associated with CNS Autoimmune Diseases. The oligoclonal, intrathecally synthesized IgG contains numerous specific antibodies and autoantibodies. Antibodies are frequently found with specificities against measles, the rubella virus and the varicella-zoster virus, but seldom against the herpes simplex virus. The occurrence of one, two, or three of these antibodies is referred to as the MRZ reaction. The corresponding antigens are not present in these cases. The MRZ reaction is typical of multiple sclerosis as well as cerebral lupus erythematosus and is a chronically evolving immune process (F5, K10, S16). An increased IgM index is seen in cerebral lupus erythematosus and in 30-60 of multiple sclerosis patients with a short disease duration (A20, A24, L1). An increase in the IgM index is usually associated with oligoclonal IgM bands on electrophoresis. This indicates an oligoclonal aspect of intrathecally produced IgM. Cerebral IgM production is related to...

Pharmacophorebased Virtual Screens

Inhibitors of mesangial cell proliferation (MCP) are thought to be useful in the treatment of glomerular diseases such as diabetic nephropathy and lupus (22). Kurogi and co-workers (22) discovered a novel series of MCP inhibitors through construction of a pharmacophore from four benzylphosphonate compounds (represented by 6) with significant MCP inhibitory potency. The Catalyst pharmacophore consisted of two aromatic rings, two hydrophobic sites, and three hydrogen-bond acceptor sites. A search of the Maybridge database (23) of 47,045 compounds gave rise to 41 hits. Four of the best fitting compounds were tested for MCP inhibitory activity and demonstrated potency comparable to compounds in the original training set (exemplified by 7). Additionally, the new lead compounds were devoid of the cell toxicity present in the original series of compounds that were used to build the pharmacophore model.

Therapeutic Potential Of Dppiv Inhibition

Nervosa and periodontal disease, but are decreased in systemic lupus, rheumatoid arthritis, pregnancy, depression, and schizophrenia (91-98). HIV-infected patients have normal serum DPP-IV activity but with a decreased number of DPP-IV-positive lymphocytes (99). DPP-IV has been employed as a cell surface marker in the histological evaluation of a wide range of tumor types. Tumors have been described with either increased or decreased expression of CD26 DPP-IV, and this divergent expression has been associated with both an increased and decreased aggressiveness of growth of the tumors in question. Tumors with high cell-surface DPP-IV activity expression include B chronic lymphocytic leukemia, basal cell carcinoma, T cell lymphoma, thyroid carcinoma, breast cancer, hepatocellular carcinoma, and lung tumors, while tumors with reduced or absent DPP-IV activity CD26 expression include squamous cell carcinoma and melanoma (88,100108). Presently, it is unclear whether changes in DPP-IV...

Osteonecrosis Avascular Necrosis or Aseptic Necrosis

Asherson RA, Khamashta MA, Gil A, Vazquez JJ, Chan O, Baguley E, Hughes GR (1989a) Cerebrovascular disease and antiphos-pholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome. Am J Med 86(4) 391-399 Asherson RA, Khamashta MA, Baguley E, Oakley CM, Rowell NR, Hughes GRV (1989b) Myocardial infarction and antiphos-pholipid antibodies in SLE and related disorders. Q J Med 73(272) 1103-1115 Asherson RA, Higenbottam TW, Dinh Xuan AT, Khamashta MA, Hughes GRV (1990) Pulmonary hypertension in a lupus clinic experience with twenty-four patients. J Rheumatol 17(10) 1292-1298 Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa MC, Piette JC et al (2003) Catastrophic antiphospholipid syndrome international consensus statement on classification criteria and treatment guidelines. Lupus 12(7) 530-534 Asherson RA, Frances C, Iaccarino L, Khamashta MA, Malacarne F, Piette JC et al (2006) The antiphospholipid antibody syndrome diagnosis, skin...

Subcutaneous Tcell lymphoma

It seems likely that at least some of the cases diagnosed in the past as lupus panniculitis (lupus erythematosus profundus) or 'benign panniculitis evolving into overt lymphoma' represent examples of subcutaneous T-cell lymphoma with a slow progression 22 . In this context, it has been proposed recently that lupus panniculitis and subcutaneous T-cell lymphoma represent two ends of a spectrum of the same entity 23 . However, we have never observed progres sion from true lupus panniculitis to subcutaneous T-cell lymphoma and strongly believe that these two entities are completely distinct (see also Chapter 20). Cases showing 'progression' were most likely examples of subcutaneous T-cell lymphoma from the outset.

Other Effects Of Thalidomide

In addition to its antiangiogenic activity, other effects of thalidomide have been reported. Thalidomide has been used in the treatment of lepromatous reaction (51-54), graft-versus-host disease (55-60), lupus erythematosis, Behcet's syndrome (61), rheumatoid arthritis (62,63), and Crohn's disease (64,65). Thalidomide has been shown to prolong graft survival in rat cardiac transplants (66,67) and to inhibit HIV replication (68). Macrophages appear to be a cellular target of thalidomide, since the drug has been shown to inhibit lipopolysaccharide-induced tumor necrosis factor-a production (69) by selective degradation of TNF-a mRNA (70), a pleiotropic cytokine that plays a central

Treatment of Venous Sinus Obstruction

Hunt et al. 68 reported two cases of papilloedema secondary to what was reported to be venous sinus thrombosis. In both cases patients developed right sided venous sinus thrombosis. The first patient had systemic lupus erythematosis and the second had undergone a right radical neck dissection. In both cases left sided focal venous obstruction was also demonstrated one patient in the sigmoid sinus and one in the transverse sinus. Thombolysis was not followed by clinical improvement in either case. Therefore the left sided focal stenosis was stented in both cases with good effect and resolution of papilloedema. Detail regarding the anatomical arrangement of the cerebral venous system in these cases was not provided.

Fc Receptor Structure and the Design of Antiinflammatories New Therapeutics for Autoimmune Disease

Introduction - Inflammation caused by immune complexes in the blood vessels (vasculitis), the kidney (glomerulonephritis) and in the joints (arthritis) is a major cause of morbidity in autoimmune diseases. It is also one of the major mechanisms of tissue destruction in diseases including rheumatoid arthritis especially in the extra articular disease, immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE) and Wegner's granulomatosis. Whilst clear that in autoimmune diseases the likely initiation of the autoimmune process is a corruption of T cell regulation, the tissue damage and the perpetuation of disease are due to immune complexes. In the last decade, the role of Fc receptors as major initiators of inflammation caused by immune complexes has become more precisely defined with the use of recombinant Fc receptor (FcR) and gene knock-out or transgenic mice (1-8).

Clinical trials of antagonists of MCP1CCR2

Other clinical trials with CCR2 antagonists are underway 1 , but no reports have been forthcoming. Both MLN-1202, a humanized anti-CCR2 antibody, and MK-0812, a small molecule antagonist, were examined in rheumatoid arthritis (vide supra) and are also being examined in multiple sclerosis. Two additional small molecules - CCX-915 and INCB-8696 - have entered phase 1 trials with multiple sclerosis as a projected phase 2 trial. An intention to study INCB-8696 in systemic lupus erythematosus has also been declared. Finally, phase 2 clinical

Catastrophic Antiphospholipid Syndrome

Laboratory confirmation of the presence of antiphospholipid antibodies (lupus anticoagulant or anticardiolipin antibodies) Lupus anticoagulant (80 ) or and Anticardiolipin antibodies (85 ) Thrombocytopenia (60 ) < 100,000 mm ANA positive (50 ) Hemolytic anemia (25-30 )

Other cutaneous pseudolymphomas

Hemangioma Scalp Infant Histology

Previous paragraphs, the occurrence of other skin conditions simulating clinically and or histopathologically cutaneous lymphomas has been reported sporadically. Cases of inflammatory lesions of vitiligo and of eruption of lymphocyte recovery with histopathological features mimicking those of mycosis fungoides have been observed 99,100 . A condition termed 'annular lichenoid dermatitis of youth' has been reported recently as a simulator of mycosis fungoides, but it may in truth represent a variant of this disease in children 101 . Besides the entities listed in the paragraph on CD30+ cutaneous pseudolymphomas (see p. 163), we have rarely observed the presence of dense lymphoid infiltrates with scattered CD30+ cells in skin lesions of mycotic infections. True B-cell pseudolymphomas have been observed at the site of previous herpes zoster eruptions 102 . However, it must be stressed that only a few cases of clear-cut pseudolymphoma have been documented in association with herpes zoster...

Interference with lymphocyte activation

And those of other groups, in vivo statin treatment prevented and reversed disease progression in murine EAE (Aktas et al., 2003), collagen-induced arthritis (CIA) (Leung et al., 2003), and systemic lupus erythematosus (SLE) (Lawman et al., 2004). Leung and colleagues showed a marked decrease in development of CIA following simvastatin therapy, using doses that were unable to significantly alter cholesterol concentrations in vivo. Together with Youssef et al. (2002), our group has reported that atorvastatin prevents and reverses chronic and relapsing paralysis in murine EAE by targeting Th1 cells. It has been proposed that statins are therapeutically active in EAE by inducing the secretion of Th2 anti-inflammatory cytokines (IL-4, IL-5, and IL-10) and transforming growth factor (TGF)-p, and, conversely, by suppressing Th1 proinflammatory cytokines (IL-2, IL-12, IFN-g, and TNF-a) (Aktas et al., 2003 Nath et al., 2004 Youssef et al., 2002). Additionally, adoptive transfer of induced Th2...

Epidemiology And Risk Factors

Hypercoaguable states can be either inherited or acquired. Deficiencies of protein C, protein S, and antithrombin III can be inherited as autosomal-dominant conditions or acquired via inflammatory states, liver disease, disseminated intravascular coagulation, L-asparaginase therapy, and vitamin K deficiency. Deficiency of one of these anticoagulants is found in 2 to 12 of CVT patients (15,18,19). Activated protein C resistance can be inherited or acquired and is most commonly caused by factor V Leiden mutation (20). Factor V Leiden and prothrombin G20210A mutations are the most common inherited hypercoagulable states associated with CVT (10-20 of CVT patients) (15). Women who take OCs and who have genetic hypercoaguable predisposition, (e.g., factor V Leiden or prothrombin gene mutation) have an increased risk of developing CVT, compared to women of the same age who do not take OCs and do not have the factor V defect (21). An increased risk of CVT has also been reported in pregnant or...

Leptin and the hygieneaffluence hypothesis in autoimmunity

Insulin Resistance Images

Fewer infections and more autoimmunity, observed in affluent countries, lead us to postulate the so-called leptin hypothesis to explain this phenomenon (42). During the past century, in the industrialized world, the incidence of infections has diminished greatly because of improved hygienic conditions, better nutrition, vaccination, and the use of antibiotics (42). Interestingly, in affluent and more-developed societies, epidemio-logical studies have revealed a parallel increase in the incidence of autoimmune diseases, whereas these diseases have become less common in less-developed nations. Thus, susceptibility to infection and autoimmunity appear to be inversely related (42). Several factors other than nutrition might contribute to this relationship, such as the environment, genetic background, other hormones, stress, and exposure to specific pathogens (Fig. 1). Nevertheless, changes in diet and calorie intake and, subsequently, serum leptin concentrations should be taken into...

Mediators of Inflammation

Shown that a variety of other cells and tissues are also capable of producing these cytokines. For instance, endothelial cells, adipose tissue, Kupffer cells, and glial cells are capable of producing them. Endotoxin and other microbial products, immune complexes, physical injury, and a variety of inflammatory stimuli can stimulate TNF-a and IL-1 secretion. They activate endothelial cells, stimulate leukocytes, and fibroblasts, and induce systemic acute-phase reactions. Activation of endothelial cells by TNF-a, IL-6, and IL-1 induces a spectrum of changes, mostly regulated at the level of gene transcription. These induce the synthesis of endothelial adhesion molecules and chemical mediators of inflammation such as other cytokines, chemokines, growth factors, eicosanoids, and NO 35 . These events increase the thrombotic tendency on the surface of the endothelium. TNF-a primes neutrophils, leading to augmented responses of these cells to other mediators, and stimulates neutrophils to...

Relationship between Atherosclerosis and Hyperhomocysteinemia

A number of prospective studies have reported the risk estimates of arterial events or vascular and or total mortality conferred by homocysteine in populations without vascular disease at baseline 4-29 . A careful meta-analy-sis of relevant studies by the Homocysteine Studies Collaboration focused on the association between homocysteine concentration and risk of ischemic heart disease and stroke in populations without existing cardiovascular disease, diabetes mellitus, renal disease or systemic lupus erythematosus 51 . The meta-analysis showed that a 25 lower plasma homocysteine (about 3 mol l) was independently associated with an 11 (95 CI 4-17 ) lower risk of ischemic heart disease, and a 19 (95 CI 5-31 ) lower risk of stroke (fig. 1). Studies that were published after this report do not substantially differ from these results 16, 18, 26-29 . Overall, plasma homocysteine, therefore, seems to be a modest, but significant independent predictor of arterial occlusive disease in...

History

The antiphospholipid syndrome (APS), first described in 1983 by Dr. Graham Hughes and his team at the Hammersmith Hospital, included recurrent arterial and venous thromboses, fetal losses, and thrombocytopenia in the presence of autoan-tibodies, the so-called antiphospholipid antibodies (aPL). Although a wide variety of clinical manifestations have been added over the last 5 years, these major features have stood the test of time. Many patients with APS have clinical and laboratory features common to other autoimmune diseases, particularly systemic lupus erythematosus (SLE). Such patients are defined as having secondary APS to distinguish them from patients with features of APS alone (primary APS-PAPS). There appears to be very few differences, if any, between the clinical complications associated with the primary and the secondary form of the syndrome, and the rates of arterial or venous thrombosis or fetal loss do not appear to be different. Distinguishing between PAPS and APS due...

Epidemiology

In autoimmune diseases, especially SLE, however, the prevalence is much higher. The Euro-Lupus study found a prevalence of 24 for IgG anticardiolipin antibody (aCL), 13 for IgM aCL, and 15 for lupus anticoagulant (LA), respectively, in a cohort of 1,000 patients with SLE. A recent study showed that the prevalence of antiphospholipid syndrome (APS) increases from 10 to 23 after 15-18 years in a large cohort of SLE patients. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P et al (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period a comparison of early and late manifestations in a cohort of 1, 000 patients. Medicine (Baltimore) 82(5) 299-308 Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT et al (2002) Antiphospholipid syndrome clinical and immunologic manifestations and patterns of disease expression in a cohort of 1, 000 patients. Arthritis Rheum 46(4) 1019-1027

Cerebral Ischemia

Cerebral ischemic disease associated with aPL is the most common arterial thrombotic manifestation. Stroke and transient ischemic attacks (TIAs) are considered the second most common clinical manifestations of APS after venous trombosis (Fig. 7.1). Moreover, in the European Working Party on systemic lupus erythematosus (SLE) (which studied a cohort of 1,000 patients with SLE), thromboses were the most common cause of death during follow up and were always

Clinical Examination

The clinical examination of the eyes for signs of ocular allergy begins with the external components that surround the eye and the eye itself. First, one examines the eyelids and eyelashes, focusing on the presence of erythema on the lid margin, as well as telangiectasias, scaling, thickening, swelling (blepharitis, dermatitis), and collarettes of debris at the base of the eyelashes, and evidence of periorbital discoloration, blepharospasm, or ptosis. Next, the conjunctivae are directly examined for chemosis (clear swelling), hyperemia (injection), palpebral and bulbar papillae, and cicatrization (scarring). The discharge from the eye is also noted for increase or discoloration. It is important to differentiate this from the injection associated with inflammation of the sclera (scleritis) that tends to develop over the course of several days. Scleritis is also commonly associated with autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, and Wegener's...

Role in inflammation

Many forms of immune-mediated nephritis in humans, including lupus nephritis, are associated with an expanded population of renal macrophages and increased tubular and glomerular expression of CSF-1. A negative correlation exists between renal CSF-1 and creatinine clearance 33 . Plasma CSF-1 is elevated in patients with systemic lupus 34 , and persistently high levels of CSF-1 in urine after initial remission, is a predictor of renal flares 35 . MRL-Faslpr mice exhibit spontaneous lupus-like disease including nephritis and cutaneous lesions together with increased local and systemic levels of CSF-1. Transgenic overexpression of CSF-1 exacerbates disease, and CSF-1-nullizygous mice demonstrate resistance 36,37 . Because UVB light triggers cutaneous lesions in wild-type but not in CSF-1-deficient MRL-Faslpr mice 37 , FMS inhibitors might find additional application treating the subset of patients with cutaneous disease.

Other Compounds

Experimental models of lupus and diabetes than methimazole 98 . The phenyl analog inhibited TNF-a-induced VCAM-1 mRNA and protein expression in human airway epithelial cells (HAECs), reduced TNF-a-induced monocytic (U937) cell adhesion to HAECs under in vitro flow conditions, inhibited TNF-a-induced interferon regulatory factor-1 (IRF-1) binding to VCAM-1 promoter, and reduced TNF-a-induced IRF-1 expression in HAECs 95 .

Autoimmune disorders

4.2.1 Rheumatoid arthritis (RA), multiple sclerosis (MS) and systemic lupus erythematosus (SLE) SLE is a chronic relapse and remitting autoimmune disease that affects multiple organ systems including the skin, joints, kidneys and nervous system. It initially manifests as fever, malaise, joint pains, myalgias and fatigue, and is virtually always accompanied by the presence of a diverse but characteristic set of autoantibodies 38 . In addition to organ-specific damage mediated by IC-triggered macrophage and neutrophil activation, Syk can potentially affect SLE pathophysiology in several other ways. The genetic contributions to disease susceptibility and severity are complex and involve multiple traits that implicate abnormalities of both the innate and adaptive immune systems 38 . Microarray studies with peripheral blood leukocytes from SLE patients have helped identify ''gene signatures'' typically found as a result of the action of type I interferons (IFNs) 39,40 . Interestingly, ICs...

Chronic hepatitis

Chronic persistent hepatitis is usually unaffected by pregnancy. Chronic active hepatitis is associated with impaired fertility if pregnancy does occur it may be associated with accelerated deterioration in liver function. Treatment includes corticosteroids and antiviral drugs, including interferon. Lupus antibodies may occur in up to 20 of women with chronic active hepatitis. Chronic active hepatitis may be complicated by arthritis, impaired renal function, myocarditis and neuropathies. Diabetes, hypertension and osteoporosis may also occur as a result of long-term steroid therapy.

Tetracyclines

The side effect profile (Table 2) of doxycycline and minocycline also differs, most notably in the incidence of photosensitivity with doxycycline and the occurrence of hypersensitivity reactions with minocycline. Photosensitivity is very common at higher doses of doxycycline. The minocycline hypersensitivity reactions are uncommon and include urticaria, serum sickness-like reactions, and what has been termed a lupus-like reaction that in reality is probably not an activation of systemic lupus erythematosus but a generalized drug-induced reaction that resembles lupus (34).

Heparin

Should include detailed medical and obstetric history, documentation or confirmation of significant levels of aPL, review of medication, information of maternal and obstetric problems' risk and information of possible further treatments, blood tests (renal, blood cell count, liver, urine, ). In those who have systemic lupus erythematosus (SLE), issues related to exacerbation of SLE also should be discussed. All patients should be assessed for evidence of anemia and thrombocytopenia, which occur in association with APS.

Thalbom3de

Thalidomide is a potent teratogen that causes dysmelia (stunted limb growth) in humans. It was marketed as a sedative, but was withdrawn from the European market 30 years ago because of its teratogenic effects. The compound was later discovered to be extremely effective in lepromatous leprosy and has been used routinely for that indication around the world. In addition, trials have recently been initiated in a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency patients, graft-vs-host disease (GVHD), lupus erythematosus, tuberculosis, wasting syndrome associated with HIV infection, and rheumatoid arthritis. Renewed interest in thalidomide has been generated following the publication of in vitro data suggesting it has antiangiogenic properties (6). Based on those data, four solid tumor trials were initiated by the NCI (7). Currently, more than 1000 patients in the United

Side Effects

As discussed above, thalidomide has been used for the treatment of leprosy, graft versus host disease, rheumatoid arthritis, aphthous ulcers associated with AIDS, and various dermatologic disorders. The side effects of thalidomide have been well documented and they include drowsiness, constipation, peripheral sensory neuropathy, swelling of the limbs, erythema of the limbs, hair loss, fever, rash, and amenorrhea. Dizziness and mood changes occurred in 33-100 of all patients. Other frequent adverse effects are xerostomia, increased appetite, loss of libido, nausea, pruritus, and menstruation abnormalities have been occasionally observed. The most serious of these side effects is peripheral neuropathy. Its incidence has been estimated to be approx 1 in patients treated for lepra reactions (81), 12 in rheumatoid arthritis (65), 22 in prurigo nodularis (66), and 25 in patients with discoid lupus erythematosus (67). Based on electrophysiologic studies the incidence was estimated at 21...

Conclusions

Faber-Elmann, A., Sthoeger, Z., Tcherniack, A., Dayan, M., and Mozes, E., Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus. Clin. Exp. Immunol. 127, 393-398 (2002). K9. Kotajima, L., Aotsuka, S., Fujimani, M., Okawa-Takatsuji, M., Kinoshita, M., Sumiya, M., and Obata, K., Increased levels of matrix metalloproteinase-3 in sera from patients with active lupus nephritis. Clin. Exp. Rheumatol. 16, 409-415 (1998). Z12. Zucker, S., Mian, N., Drews, M., et al., Increased serum stromelysin-1 in systemic lupus erythematosus Lack of correlation with disease activity. J. Rheumatol. 26, 78-80 (1999).

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