摘要:

Plant extracts with a high content of proteolytic enzymes have been used in traditional medicine for a long time. Besides herbal proteinases, ‘modern’ enzyme therapy includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is empirically based, but is also supported by scientific studies. This review provides an overview of preclinical and clinical trials of systemic enzyme therapy in rheumatic disorders. Studies of the use of proteolytic enzymes in rheumatic disorders have mostly been carried out on enzyme preparations consisting of combinations of bromelain, papain, trypsin and chymotrypsin. The precise mechanism of action of systemic enzyme therapy remains unresolved. The ratio of proteinases to antiproteinases, which is affected by rheumatic diseases, appears to be influenced by the oral administration of proteolytic enzymes, probably via induction of the synthesis of antiproteinases or a signal transduction of the proteinase-antiproteinase complex via specific receptors. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes resulting from immunomodulatory effects, which might be an indication of the efficacy of enzyme therapy.The results of various studies (placebo-controlled and comparisons with nonsteroidal anti-inflammatory drugs) in patients with rheumatic diseases suggest that oral therapy with proteolytic enzymes produces certain analgesic and anti-inflammatory effects. However, the results are often inconsistent. Nevertheless, in the light of preclinical and experimental data as well as therapeutic experience, the application of enzyme therapy seems plausible in carefully chosen patients with rheumatic disorders.

ISSN:1173-8804    

出版商:ADIS    

年代:2001

数据来源: ADIS

摘要:

Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC.

ISSN:1173-8804    

出版商:ADIS    

年代:2001

数据来源: ADIS

摘要:

Primary pulmonary hypertension (PPH) is a rare disorder of the lung vasculature characterised by an increase in pulmonary artery pressure. Although the aetiology of this disease remains unknown, knowledge of the pathophysiology of the disease has advanced considerably. Diagnosis of PPH is largely by exclusion. The clinical symptoms associated with PPH are aspecific and similar to those seen in other cardiovascular and pulmonary diseases. Electrocardiography, echocardiography, pulmonary function tests, and a lung perfusion scan are necessary to exclude secondary forms of pulmonary hypertension and also help to confirm the diagnosis of PPH. A definite diagnosis of PPH is established by right-heart catheterisation which gives a precise measure of the blood pressure in the right side of the heart and the pulmonary artery, right ventricular function and cardiac output. Once a diagnosis of PPH is established, treatment involving drug therapy or surgery is commenced on the basis of the New York Heart Association functional class. Conventional treatment consists of lifetime administration of anticoagulants, oxygen, diuretics, and digoxin. Vasodilator therapy with calcium channel antagonists is indicated in patients who are ‘vasoreactive’ to acute vasodilator challenge as assessed by right-heart catheterisation. Promising results are obtained by continuous intravenous administration of epoprostenol (prostacyclin). Newer therapies for PPH include prostacyclin analogues, endothelin receptor antagonists, nitric oxide, phosphodiesterase-5 inhibitors, elastase inhibitors, and gene therapy. Surgical treatment consists of atrial septostomy, thromboendarterectomy, and lung or heart-lung transplantation.

ISSN:1173-8804    

出版商:ADIS    

年代:2001

数据来源: ADIS

摘要:

The identification of tumour-associated antigens has opened up new approaches to cancer immunotherapy. While past research focused on CD8+ cytotoxic T-cell responses, accumulating evidence suggests that CD4+ T cells also play an important role in orchestrating the host immune response against cancer. In this article, we summarise new strategies for the identification of major histocompatibility complex (MHC) class II-associated tumour antigens and discuss the importance of engaging both CD4+ and CD8+ T cells in cancer immunotherapy. The cloning of MHC class I- or class II-associated antigens has made it possible to develop synthetic and recombinant cancer vaccines that express specific tumour antigens. There are three major types of synthetic and recombinant cancer vaccines: recombinant viral and bacterial vaccines; naked DNA or RNA vaccines; and recombinant protein and peptide vaccines. In this article, we also discuss a new generation of recombinant cancer vaccines, ‘self-replicating’ DNA and RNA vaccines. Studies on the mechanisms of ‘self-replicating’ nucleic acid vaccines revealed that the enhanced immunogenicity was not due to an enhanced antigen expression, suggesting that the quantitative difference may not be as important as the qualitative difference in antigen presentation. The presence of the RNA replicase in the ‘self-replicating’ nucleic acid vaccines mimics alphavirus infection, which triggers the innate antiviral pathways of the host cells. Studies on how viral and cellular modulators of the innate antiviral pathways affect vaccine function should provide molecular insights crucial to future vaccine design.

ISSN:1173-8804    

出版商:ADIS    

年代:2001

数据来源: ADIS

摘要:

Prevention of immunological rejection of transplanted tissues is of crucial importance in transplantation medicine. Current procedures primarily use pharmacological agents such as cyclosporin, which, while effective, must be typically administered for the life of the individual. Furthermore, the drug-induced global immunosuppression of the patient predisposes the individual to infection and enhances their risk of developing certain forms of cancer. Hence, additional methods are needed to both enhance tissue engraftment and diminish the adverse effects of current immunosuppressive therapy. Studies from blood transfusion (i.e. a specialised form of cellular transplantation) suggest that covalent modification of cells and tissues with methoxypoly(ethylene glycol) [mPEG] can significantly diminish rejection episodes and may further enhance the induction of tolerance to donor tissues. The mechanisms underlying mPEG-mediated immunocamouflage are the loss of antigen recognition, impaired cell-cell interaction, and an inability of endogenous antibodies (e.g. immunoglobulin G) to effectively recognise and bind foreign epitopes. As a consequence of the global camouflage imparted by mPEG, the weak co-stimulation of alloreactive T cells may subsequently induce apoptosis, thus leading to tolerance. Initial studies on the transplantation of pegylated isogeneic rat pancreatic islets demonstrates that mPEG-derivatisation does not impairin vivocellular signalling and function. Thus, in contrast to the pharmacological inhibition of the recipient's immune response, the mPEG-mediated immunocamouflage directly addresses the inherent antigenicity and immunogenicity of the donor tissue itself while leaving the recipient a fully competent immune system.

ISSN:1173-8804    

出版商:ADIS    

年代:2001

数据来源: ADIS