Glycosaminoglycan excretion in connective tissue diseases

Abnormal glycosaminoglycan metabolism has been widely studied in cases of mucopolysaccharidoses (MPSD) with increased acid glycosaminoglycan (aGAG) excretion. A disorder in aGAG metabolism can be confirmed in several diseases with known etiology. We have carried out a comparative study on the urinary aGAG output in systemic connective tissue diseases and in childhood cases of MPSD. In children suffering from rheumatoid arthritis or scleroderma, the urinary aGAG output did not surpass 80% of the value excreted in MPSD; furthermore, 20 to 30% was uronic acid. In the case of osteogenesis imperfecta the remarkably high amount of excreted aGAG contained over 60% uronic acid.     

Synthetic glucocorticoid in the treatment of connective tissue diseases

Synthetic glucocorticoids are the most potent anti-inflammatory and immunosuppressive drugs, which have been used for almost 50 years as a core drug for the treatment of connective tissue diseases. The mechanism of action of glucocorticoids as anti-inflammatory or immunosuppressive drug is considered as the repression of inflammatory cytokines, receptors of cytokines, and adhesion molecules. When 60 mg of prednisolone is administered in 3 divided doses, the plasma concentrations are around 20-30 micrograms/dl during the day time, in which condition around 90% of GC receptors are occupied. However, the concentration will decrease almost to 0 microgram/dl in the next early morning. In case of methyl prednisolone pulse therapy, about 40 micrograms/dl of the steroid is present in the next morning. These kinetics are important when we consider the glucocorticoid therapy. In the treatment of connective tissue diseases, the combination of the steroid therapy with the immunosuppressive therapy should always be considered. In diffuse proliferative lupus nephritis, glucocorticoid dosage, started at high level to suppress the clinical activity of SLE, decrease rather rapidly while cytotoxic drugs are administered at least for 2 years. In the treatment of systemic sclerosis, normotensive scleroderma kidney is treated with moderate dose of glucocorticoid and cytotoxic drugs. It is our clinical impression that low dose glucocorticoid is quite effective in the treatment of rheumatoid arthritis. However, low dose glucocorticoid therapy is effective for the patient's sense of well-being, but is scarsely effective for the articular symptoms itself and shows intense rebound phenomenon when glucocorticoid is withdrawn.     

Intestinal microbiocenosis in systemic connective tissue diseases

The purpose of the investigation was to study the quantitative and qualitative composition of colon microflora in system connective tissue diseases and system vasculites. The authors studied colon microflora in patients with systemic lupus erythematosus, systemic scleroderma, nodular polyarteritis, and hemorrhagic vasculitis. The structure of symbiotic interrelations between microorganisms participating in the formation of colon microbiocenosis was determined. Colon microflora was found to be disordered in terms of its qualitative and quantitative composition. The predomination of anaerobic microorganisms was decreased, while the role of conditionally pathogenic bacteria was increased. The number of lactobacteria was significantly lowered; bifidobacteria and bacteroids were found frequently, while their number was substantially lowered as well. Conditionally pathogenic microorganisms and bacteria with hemolytic activity acquired high significance in the forming of the colon microbiocenosis of the patients. The frequency of the isolation and the density of colon colonization with staphylococci and conditionally pathogenic enterobacteria were significantly increased. General trends and peculiarities of changes in the quantitative and qualitative composition of colon microflora in some rheumatic diseases were determined. The data on the peculiarities of the colon microbiocenosis in these patients may be used to substantiate methods of complex therapy including correction of dysbiotic disturbances.     

Immunosuppressive treatment strategy in connective tissue diseases

In this review, we summarized important articles published about immunosuppressive agents in connective tissue diseases. Intravenous cyclophosphamide therapy for lupus nephritis and oral cyclophosphamide therapy for Wegener's granulomatosis are major progress in past one decade. Newer immunosuppressive agents such as cyclosporin, tacrorimus are also introduced in steroid refractory organ involvements. And we discussed also the monitoring and prevention of adverse effects of immunosuppressive agents. This review will focus on immunosuppressive treatment strategy of connective tissue diseases.     

Prostaglandins in the pathogenesis of various systemic diseases of the connective tissue

A study was made of the content of prostaglandins E, A, F2 alpha and malonic dialdehyde (MDA) in the blood plasma and urine of patients with systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis and healthy persons. The levels of plasma and urine prostaglandins and MDA were significantly elevated in systemic lupus erythematosus and rheumatoid arthritis, and in systemic scleroderma they did not differ from those in normal. The ratio of pressor and depressor prostaglandins in systemic lupus erythematosus and rheumatoid arthritis did not change, and in systemic scleroderma there was a strong shift to pressor prostaglandins. Change in the content and ratio of prostaglandins and MDA in systemic diseases of connective tissue was suggestive of differences of pathogenetic effects of these mediators in some diseases of this group.     

Pulmonary hypertension in patients with connective tissue diseases]

Pulmonary hypertension (PH) is said to be frequently associated with connective tissue diseases (CTD). The national surveillance of CTD associated PH (CTD-PH) by the study groups of the Ministry of Health and Welfare (MHW) revealed that mixed connective tissue disease (MCTD) had the highest incidence of PH (5.02%), next to systemic sclerosis (SSc) (2.64%). Patients with CTD-PH could be divided into two groups according to the prognosis: poor prognosis group and fairly good prognosis group. Poor prognosis was associated statistically with polyarthritis and high level of CK. Treatment of CTD-PH was still difficult, but adrenocoticosteroids could be tried in some patients, and drip infusion therapy of prostacyclin seemed very promising, but it has not been accepted by the MHW so far.     

超敏C-反应蛋白在结缔组织疾病诊断中的临床价值

目的了解超敏C-反应蛋白（hs—CRP）在结缔组织病急性期中的变化。方法回顾性分析98例结缔组织病患者急性期血中hs—CRP、白细胞计数、红细胞沉降率（下称血沉）等检测结果,同时与67例感染性疾病比较。结果98例结缔组织病患者hs—CRP升高68例（69．4％）,白细胞同时升高13例（19．1％）,血沉同时升高48例（70．6％）;67例感染性疾病患者hs—CRP升高57例（85．1%）,白细胞同时升高44例（77．2％）,血沉同时升高36例（63．2％）。结论结缔组织病急性期,hs—CRP大多升高,并与血沉增快一致,但白细胞多数正常,与感染性疾病不同。