Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor (TNFalpha) is a cytokine with a wide range of diverse and at times paradoxical effects. These include immunoregulatory, lymphoid organogenesis and pro-inflammatory effects. In recent years, TNFalpha has become a focus of interest more for its inflammatory effects in a number of chronic autoimmune diseases. This interest culminated in the successful treatment of patients with rheumatoid arthritis, Crohn's diseases and ankylosing spondylitis with blocking antibodies or soluble TNFalpha receptors. Paradoxically, however, TNFalpha also has immunomodulatory effects in some autoimmune conditions such as lupus in some mouse models of the disease and in diabetes in the none-obese diabetic mouse. The role TNFalpha plays in human systemic lupus erythematosus is, however, controversial. In this article we review some of the studies carried out to elucidate the effects of TNFalpha in lupus disease and likely mechanisms of action. Further, we discuss recent data on the likely effects of blocking TNFalpha on anti-DNA autoantibody production.
Lupus 2002
PMID:Tumour necrosis factor alpha in systemic lupus erythematosus and anti-DNA autoantibody production. 1252 50

Psoriasis is a life-disabling disorder in which 8-10% of patients aged 18-54 actively contemplate suicide because of their disease. Owing to the toxicity and/or inconvenience of current, FDA-approved treatments far moderate-to-severe psoriasis, they are generally used intermittently so that patients experience cycles of remission-flare-remission-flare, etc. The challenge to drug development for moderate-to-severe psoriasis is to provide safe and effective long-term management. Immunobiologics offer the hope for safe, long-term control of psoriasis because they lack targeted organ toxicity. Thus the treatment paradigm may shift from one of intermittent treatment limited by toxicity with resultant flares of disease, to one similar to that seen in diabetes or hypertension in which disease is controlled continuously. Additionally, immunobiologics may alter the natural history of psoriasis. Etanercept, which targets TNF-alpha, controls signs and symptoms and halts joint destruction in patients with psoriatic arthritis. The long-lived remissions observed after cessation of alefacept or infliximab (anti-TNF-alpha monoclonal antibody) treatment lead this author to speculate that these immunobiologics may actually alter the natural history of the cutaneous manifestations of psoriasis.
Lupus 2003
PMID:Clinical research helps elucidate the role of tumor necrosis factor-alpha in the pathogenesis of T1-mediated immune disorders: use of targeted immunotherapeutics as pathogenic probes. 1270 79

We studied the clinical course of 26 systemic lupus erythematosus (SLE) patients who started regular dialysis at our hospital and whose stay exceeded a three-month duration in order to investigate the long-term prognosis in a Chinese cohort. Clinical and serological activities of lupus before and after dialysis were analysed. To compare the long-term survival rate, controls were set using 78 age-matched end-stage renal disease (ESRD) patients who did not have SLE or diabetes mellitus and entered the chronic dialysis program at a similar period with SLE dialysis patients. There was a significant decrease in clinical lupus activity after starting regular dialysis (P < 0.05); however, the serological activity remained the same. The five-and ten-year survival rates were significantly lower in the SLE patients (73 and 38% in the SLE group versus 95 and 88% in the non-SLE group, P < 0.05). SLE patients had a 4.3-times higher risk of death than non-SLE patients (P < 0.05, 95% confidence interval, 1.2-15.2). Also, the deceased SLE patients had persistent lower serum levels of complement 3. SLE patients with ESRD remain clinically quiescent despite persistent serological abnormalities and have a worse prognosis than other uremia patients in the Chinese population.
Lupus 2003
PMID:Poor prognosis of end-stage renal disease in systemic lupus erythematosus: a cohort of Chinese patients. 1466 98

Diabetic retinopathy (DR) is a major cause of blindness in the working population of the Western world and there is no doubt that its prevalence is strongly related to the duration of diabetes and the glycemic control. However, although intensive diabetes management, with the goal of achieving near-normal glycemia, has been shown to prevent and/or delay the onset of DR, there is now ample of evidence that the development of this microangiopathy is a multifactorial process in which genetic, metabolic, haemostatic and growth factors play an important role. Moreover, given the suggestions that immunological mechanisms might have a role in the pathogenesis of diabetic microangiopathy via immune complex deposition, it has been hypothesized that antiphospholipid antibodies (A-Ab) directed against endothelial antigens could be responsible for initiating vascular injury. In particular, not only A-Ab production was found to be increased in patients with overt nephropathy or macroangiopathy but also Lupus Anticoagulant positivity, representing an intersection point between immune and haemostatic alterations, has been highlighted as a potential and additional risk factor in the pathogenesis of microangiopathy in type 1 diabetics. Moreover, given the high levels of activated protein C, endothelin-1 and thrombo-modulin that have been observed in normo-albuminuric and uncomplicated patients, it has been concluded that the vascular endothelium shifts pathologically from an antithrombotic to a prothrombotic state even in the early phases of the disease. This condition was found to be more pronounced in subjects with anticardiolipin positivity and/or high circulating immune complexes concentrations, since they possess the ability not only to induce platelet activation and aggregation but also to activate the complement system via the classical pathway. Therefore, a potential synergism between generation of autoantibodies, haemostatic alterations and endothelial stress has been suggested, a stimulating hypothesis that needs further studies to be clarified in its complexity.
 ...
PMID:Are phospholipid-binding antibodies implicated in the pathogenesis of diabetic microangiopathy? 1523 81

The American College of Rheumatology renal criteria require re-evaluation to incorporate recent advances in the classification of glomerulonephritidies. Renal biopsy is now common and safely performed by experienced nephrologists in community as well as academic settings. The optimal criterion is renal histopathology findings of an immune complex mediated glomerulonephritis as interpreted by an experienced pathologist employing accepted criteria. Renal biopsies should be analysed by routine histopathology, immunofluorescent and electron microscopy. Rating of activity and chronicity should be noted. Secondary criteria for patients unable to undergo renal biopsy includes a combination of findings. These include proteinuria, hypocomplementemia, elevated anti-dsDNA antibodies and an active urine sediment. Proteinuria is a nonspecific finding and, most importantly, can be associated with a number of comorbidities including diabetes, hypertension and atherosclerotic disease. Persistent proteinuria > 0.5 g per day or a spot protein to creatine ratio of > 0.5 should be accompanied by an additional feature supporting active lupus such as positive serologies (hypocomplementemia and/or elevated anti-dsDNA antibodies) and/or active urinary sediment. Similarly, active urinary sediment should be accompanied by the additional criterion of proteinuria to meet renal criteria. Decline in renal function is not a reliable criterion given the numerous medications, comorbidities and other clinical circumstances which may result in this feature.
Lupus 2004
PMID:Review of ACR renal criteria in systemic lupus erythematosus. 1558 Sep 82

The objective of this study was to evaluate the early damage as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in Brazilian systemic lupus erythematosus (SLE) patients with disease duration of 2 and 3 years and to evaluate the possible association between SLICC/ACR DI score and sociodemographic and clinical data. The SLICC/ACR DI was measured in 54 patients with SLE according to the ACR criteria for SLE and a mean (SD) disease duration of 29 (3.8) months. The patients were provided by outpatient clinics and hospitals of the public health network and private clinics in the city of Natal in Brazil. The SLICC/ACR DI scores for each type of organ damage, prevalence of damage within organ systems, and the association with sociodemographic variables were assessed. Disease duration was considered as the time from diagnosis until the study. Organ damage was present in 18 (33%) of the 54 patients while 36 patients (67%) had no damage. The skin (11%), renal (9%), and pulmonary (7.4%) systems were the most frequently involved, followed by the neuropsychiatric and musculoskeletal systems, premature gonadal failure, and diabetes. The most frequent individual items on the SLICC/ACR DI were scarring chronic alopecia and pleural fibrosis. No association was demonstrated between organ damage (SLICC/ACR scores) and sociodemographic and clinical variables. Early organ damage demonstrated in Brazilian patients with SLE was similar to other populations studied in the world, despite a low socioeconomic status. In contrast to reports in other studies, a cutaneous lesion was the most frequent cause of damage in our patients.
 ...
PMID:Skin is the most frequently damaged system in recent-onset systemic lupus erythematosus in a tropical region. 1559 43

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5+/-4.7 years, and mean disease duration, 6.3+/-6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-beta2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.
Lupus 2005
PMID:Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies. 1575 19

Mycofenolate mofetil (MMF-Cellcept) is an immunomodulatory drug utilized extensively in transplant medicine. The efficacy of regimes including Cellcept in preventing allograft rejection, and in the treatment of rejection, is now firmly established. The immunosuppressive actions of this drug enabled the investigation for the beneficial effects in autoimmune diseases. We review the evidence for the contribution of MMF in autoimmunity in animal models of systemic lupus erythematosus (SLE), mercury induced autoimmune glomerulonephritis, diabetes mellitus, experimental autoimmune uveoretinitis, and experimental allergic encephalitis. MMF has an influence on the T and B cell pathways. It is immunosuppressive and anti-inflammatory.
Lupus 2005
PMID:Mycophenolate mofetil in animal models of autoimmune disease. 1580 26

beta2-glycoprotein I (beta2GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with beta2GPI and immunoreactive lymphocytes. oxLDL/beta2GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti-oxLDL/beta2GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/beta2GPI complexes were internalized by macrophages via IgG anti-beta2GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.
Lupus 2005
PMID:Oxidized LDL/beta2-glycoprotein I complexes: new aspects in atherosclerosis. 1621 78

Systemic lupus erythematosus (SLE) patients have increased cardiovascular morbidity and mortality. QT-interval parameters are presumed markers of cardiovascular risk and have not been previously evaluated in SLE. Standard 12-lead ECGs were obtained from 140 female SLE outpatients and 37 age and body mass index-matched controls. QT interval was measured in each lead and heart rate-corrected maximum QT-interval duration (QTcmax) and QT-interval dispersion (QTd) were calculated. Risk factors for cardiovascular disease and lupus clinical features, disease treatment, disease activity and damage index were recorded. SLE patients have increased QT-interval parameters when compared to controls (QTcmax: 427.91 +/- 31.53 ms(1/2) versus 410.05 +/- 15.45 ms(1/2), P < 0.001; QTd: 52.38 +/- 22.21 ms versus 37.12 +/- 12.88 ms, P < 0.001). These differences persisted after excluding those patients with arterial hypertension, diabetes and with ECG abnormalities (QTcmax: 419.90 +/- 28.78 ms(1/2) versus 409.15 +/- 15.85 ms(1/2), P = 0.041; QTd: 54.74 +/- 26.00 ms versus 37.96 +/- 13.05 ms, P = 0.001). Multivariate linear regression for factors associated with QTcmax selected the presence of electrocardiographic left ventricular hypertrophy (ECG-LVH) (P = 0.003), nonspecific ST-T-wave abnormalities (P = 0.022) and left atrial enlargement (P = 0.044). Multivariate associates with QTd were age (P = 0.018), ECG-LVH (P = 0.022) and ST-T abnormalities (P = 0.031). In conclusion, SLE patients have increased QT interval parameters when compared to controls. This prolongation may lead to an increased cardiovascular risk. This finding might be due to subclinical atherosclerotic cardiovascular disease.
Lupus 2005
PMID:QT-interval parameters are increased in systemic lupus erythematosus patients. 1630 81


<< Previous 1 2 3 4 5 6 7 Next >>