Intestinal mucosal permeability in inflammatory rheumatic diseases. I. Role of antiinflammatory drugs

Using the 51Cr-EDTA resorption test, gut permeability was measured in 129 patients with inflammatory joint diseases and in 97 control patients (42 patients with no inflammatory rheumatic disorders taking antiinflammatory medication and 55 healthy controls). Thirty-two patients (30 arthritis and 2 control patients) taking nonsteroidal antiinflammatory drugs (NSAID) as well as corticosteroids were excluded from statistical analysis. The intake of NSAID significantly increased gut permeability in controls but not in the arthritis groups. The same applied to corticosteroid intake. This could be due to the restricted number of arthritis patients who had never taken antiinflammatory drugs or to a disease related increased permeability. There was no statistically significant difference in altered gut permeability between patients taking NSAID and patients taking corticosteroids. Our findings suggest that drug induced alteration of gut permeability may not only be accounted for by an inhibition of mucosal cyclooxygenase activity, but that other enzymatic pathways in the arachidonic cascade might be implicated.     

Cardiovascular disease in inflammatory rheumatic diseases

Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.     

Prednisone effect on microvascular permeability in patients with inflammatory rheumatic diseases.

The transcapillary escape rate of albumin was measured in 27 consecutive patients with inflammatory rheumatic diseases before and after 1 and 7 days of prednisone treatment in doses of 45 mg/day. The transcapillary escape rate decreased from 7.33%/h (range 5.11-9.55) before prednisone treatment to 3.11%/h (0.04-6.18) (p less than 0.05) after 1 day of treatment and 5.80%/h (4.36-7.24) after 7 days of treatment. It is concluded that prednisone inhibits vascular permeability in patients with inflammatory rheumatic diseases.     

肠黏膜屏障与炎症性肠病

炎症性肠病（Innammatory bowel disease，IBD）是一组病因不明的慢性肠道炎症性疾病，主要包含两个独立的疾病，溃疡性结肠炎（Ulcerative colitis，UC）和克罗恩病（Crohn’s disease，CD）。近年研究发现，肠黏膜屏障功能异常在IBD发病机制中发挥重要作用。更好地了解正常及疾病状态下肠黏膜屏障的结构和功能可以为IBD的治疗提供新的思路。     

Role of mucosal dendritic cells in inflammatory bowel disease

The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells （DCs） are assumed to play key roles in regulating immune responses in the antigenrich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate （innate and adaptive） immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease （IBD）, Crohn＇s disease （CD） and ulcerative colitis （UC）. This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.     

Chronic inflammatory rheumatic diseases in black Zimbabweans.

The pattern of chronic inflammatory rheumatic diseases seen in 52 black Zimbabweans was determined. These diseases constituted 2% of all treatable chronic endemic medical diseases registered around Gweru City. Rheumatoid arthritis (RA) and gout were the commonest, 38.8% and 28.8% of the total respectively. Systemic lupus erythematosus (SLE), polymyositis, progressive systemic sclerosis, mixed connective tissue disease, ankylosing spondylitis, and Reiter's diseases were seen less frequently. While the rarity of ankylosing spondylitis was not surprising, that of SLE was striking. RA seen in Zimbabwe was as severe as in East Africa, with a mean age of onset of 43.6 (SD 9.6) years, mean ESR 67 (SD 33) mm/h, seropositivity 78%, subcutaneous nodules 10%, and overall deformities in 35% of all cases. Gout was as seen elsewhere, with a mean age of onset 41.5 (SD 7.95) years, M:F ratio 6.5:1, mean male serum uric acid 10.8 (SD 2.69) mg/dl (0.64 +/- 0.16 mmol/l). Alcohol as a precipitating and aggravating factor was supported by a high mean drunkenness score of 10.3 (SD 3.89) out of a maximum of 17. Unawareness and underdiagnosis of these diseases are still likely problems in this part of the world.     

炎症性肠病肠黏膜组织内淋巴细胞激活和效应应答

肠黏膜淋巴细胞的异常激活,导致对正常肠黏膜组织的损伤免疫应答,是炎症性肠病(IBD)发生的关键病理特征.在IBD肠道黏膜免疫反应中,固有层成为黏膜免疫应答的主要效应场所,上皮内淋巴细胞和固有层淋巴细胞发挥着重要作用,分泌淋巴细胞因子和产生免疫球蛋白.针对不同抗原,B、T淋巴细胞的激活和效应应答各异,B淋巴细胞产生多种损伤性抗体.T淋巴细胞有Th1和Th17淋巴细胞的过度反应、调节性T淋巴细胞的缺陷等,本文在此进行了相关的综合评价.     

The definition and measurement of disease modification in inflammatory rheumatic diseases

This article focuses on measures that are used to evaluate disease activity, damage, and function in three major inflammatory musculoskeletal disorders. The instruments used in rheumatoid arthritis, where most of the methodologic work has been done, are extensively discussed and instruments for the respective domains in psoriatic arthritis and ankylosing spondylitis are likewise presented.     

Metabolic syndrome in inflammatory rheumatic diseases

Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.     

Anti-ribonucleoprotein antibodies in inflammatory rheumatic diseases

Of 472 consecutive patients with inflammatory rheumatic diseases attending a unit responsible for the treatment of rheumatoid diseases, only 12 patients were found to have anti-ribonucleoprotein (RNP) antibodies. Of these, 5 patients fulfilled the criteria for the diagnosis of systemic lupus erythematosus (SLE) and 7 those of rheumatoid arthritis. Joint symptoms were the predominant clinical features and caused severe deformities requiring operations in most cases. One anti-RNP-positive SLE patient died of chronic active hepatitis.     

Lung involvement in inflammatory rheumatic diseases

This chapter describes the involvement of the lung in systemic inflammatory joint disease (IJD) with a particular focus on rheumatoid arthritis, although the topics of pulmonary involvement in ankylosing spondylitis and psoriatic arthritis are also addressed. Interstitial lung disease is the most lethal pulmonary complication of IJD and the chapter describes recent advances in both our understanding of this complication and the therapeutic options that offer real hope for improved outcomes. Although less well recognised, airways disease is just as common and its association with IJD is described in some detail, with a section devoted to the recent surge in interest in bronchiectasis. Acute pulmonary infection is common in IJD and its management is reviewed in some detail. Although pleural disease is less common than it once was, its treatment is explored. We conclude by reviewing the relationship between the drug therapies employed in IJD and their effects on the lung.     

Physical therapy in inflammatory rheumatic diseases

The physiotherapy of inflammatory rheumatic diseases is interpreted at the instance of the clinical pictures of rheumatoid arthritis, ankylosing spondylitis and progressive sclerodermia. Issuing from the clinical picture in each case the aim of therapy and the application of physiotherapy are described. For practice it is particularly referred to the significance of the temporary phases of the disease with regard to therapeutic purpose and planning of physiotherapy.     

Intestinal permeability and liver disease.

Increased intestinal permeability has for many years been implicated as a possible contributory factor in the development of encephalopathy and spontaneous bacterial peritonitis (SBP) seen in patients with cirrhosis. The majority of studies indicate that there is an increase in small intestinal permeability in cirrhotic patients and there is also evidence of an increase in patients with acute liver failure. The cause of these changes is unknown and whether they are related to the development of SBP and encephalopathy is unclear.     

Using cyclophosphamide in inflammatory rheumatic diseases

Cyclophosphamide (CYC), primarily introduced into clinical practice as an anti-cancer substance, is a potent immunosuppressive drug. Today, it is used in a number of organ- or life -threatening autoimmune diseases such as systemic vasculitides or connective tissue diseases. While being effective, CYC has a small therapeutic index and is associated with significant toxicity. CYC has been used in oncology in a variety of diseases and a lot of data has been derived from this area. This knowledge is often extrapolated to the rheumatologic settings. However, besides some similarities substantial differences between these two specialties considering the underlying diseases as well as the kind of application of the drug exist. The aim of the present review is to describe the general characteristics of the use of CYC from the rheumatologist's point of view, including pharmacologic and pharmacokinetic properties, drug interactions, toxicity and possible preventive and/or therapeutic measures; all of which are important to consider when using this particular drug in the treatment of inflammatory rheumatic diseases.     

Accelerated atherosclerosis in inflammatory rheumatic diseases

Over recent years it has become clear that patients with inflammatory rheumatic diseases are at increased risk of developing atherosclerosis. The exact causes for this are probably related in part to a general adverse effect of inflammation on atherogenesis, and in part to immune mechanisms specific to individual rheumatic diseases. This review discusses proposed mechanisms of accelerated atherosclerosis, including abnormal lipid and lipoprotein profiles, oxidative stress, enhanced apoptosis, thrombophilia, immune complexes, and increased mononuclear cell infiltration of atherosclerotic lesions, and local generation of cytokines.     

Serum immunoreactive prolyl hydroxylase in inflammatory rheumatic diseases.

Serum immunoreactive prolyl hydroxylase protein (S-IRPH) was measured in 56 patients with inflammatory rheumatic diseases, and the values were compared with those in 32 control subjects. S-IRPH was above the 95% confidence limit of the controls in about 70% of the patients with active systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Reiter's syndrome, Sjögren's syndrome, polyarteritis nodosa, or polymyositis. Raised values were observed in about half of the patients with an erythrocyte sedimentation rate (ESR) of 21-50 and in about 90% of those with ESR of over 50, whereas only about 10% of the patients with an inactive disease had an S-IRPH concentration exceeding this limit. Only 1 out of 8 patients with active ankylosing spondylitis had a raised S-IRPH value. The results support previous data indicating that significant changes in collagen metabolism occur in active connective tissue diseases. Assays of S-IRPH might be of some value in assessing the activity of these diseases and in monitoring the treatment provided.