摘要:

The search for economic alternatives for the production of recombinant immunoprophylactics has resulted in the concept of generating them in plants at relatively low cost. Two basic strategies are employed: the expression of recombinant antigens or antibodies in transgenic plants, or the presentation of small antigen epitopes on the surface of genetically modified plant viruses. Both approaches have resulted in the production of biologically active immunoprophylactics that have been shown in animal studies to protect from the development of disease symptoms. An especially interesting feature of producing vaccines in edible plant parts is the potential to use the transgenic plant as a vehicle for oral delivery. Substantial progress has been made over the past few years, and the first clinical trials have demonstrated the potential of this new technology. Future challenges are to express the immunoprophylactics at controlled, high concentrations in plants that could be grown locally where they are needed, and to develop easy and standardised administration procedures.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Leptin is a circulating hormone that is secreted in proportion to fat mass. It can reduce bodyweight by activating signalling molecules in the brain. Leptin appears to affect bodyweight primarily by decreasing food intake; there is no direct evidence that it significantly influences energy expenditure in humans. Its discovery in 1994 raised the possibility that it may be a useful, satiety-inducing, anti-obesity drug. However, treating obese patients with leptin alone does not induce substantial bodyweight loss because most obese patients are insensitive to leptin and are not leptin deficient. In combination with diet therapy, however, leptin treatment has the potential to eliminate the dramatic fall in circulating leptin levels (and the subsequent increase in hunger) caused by calorie restriction. Used in this manner, leptin may play a very useful role in the maintenance of bodyweight loss. In the future, leptin analogues and the development of compounds that increase leptin sensitivity may also prove to be valuable therapeutic approaches for obesity.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Uveitis, or intraocular inflammation, remains an ongoing challenge to ophthalmologists and patients alike. In most patients, uveitis is limited to the anterior ocular structures and is readily managed with topical steroids. The inflammatory process can extend behind the lens to involve the pars plana, the vitreous cavity, the choroid and the retina. These intermediate and posterior uveitides are relatively rare but contribute disproportionately to visual morbidity and present serious diagnostic and therapeutic difficulties.Systemic steroids constitute the first line of treatment for most sight-threatening uveitides. Their long term use is limited by universal and debilitating adverse effects. Second-line, steroid-sparing agents allow a reduction in steroid dosage. Cyclosporin and azathioprine are the main steroid-sparing agents currently in use. However, these compounds are limited by a narrow therapeutic window and significant adverse effects.This paper offers a brief discussion of some of the immune mechanisms involved in the pathogenesis of uveitis and reviews categories of investigational compounds.Inhibitors of T cell function: tacrolimus (previously FK506), licensed for use in liver transplantation, and sirolimus (rapamycin) are macrolide antibiotics. Sirolimus is a functional cytokine antagonist andin vitrostudies suggest it could be up to 100 times more potent than cyclosporin. Drug synergy between sirolimus and cyclosporin has been demonstrated, resulting in immunosuppression at lower drug doses and with fewer adverse effects.Nucleotide synthesis inhibitors: mycophenolate mofetil (MMF) and leflunomide. Human lymphocytes are only able to synthesise nucleic acidsde novo. Having no alternative or ‘salvage’ pathway, they are exquisitely sensitive to interference with thede novonucleotide synthesis enzymatic pathway. MMF is a purine synthesis inhibitor. Compared to other purine inhibitors, early data suggest that MMF is more efficacious and less toxic than azathioprine. Leflunomide is an inhibitor of pyrimidine synthesis.Monoclonal surface receptor antibodies and immunoadhesins: the IL-2 receptor is essential for clonal expansion of activated T cells; this has led to the development of anti-IL-2 receptor antibodies. Daclizumab is a genetically engineered humanised IgG1 monoclonal antibody. In conjunction with cyclosporin, it significantly reduces renal allograft rejection rates and is also showing promise in the treatment of T cell mediated autoimmune disorders. The mechanism of action of monoclonal antibodies to other pro-inflammatory cytokines such as TNFα and IL-12 and data from animal and human uveitis trials are also discussed. Finally, new avenues of research in immunopharmaco-modulation are mentioned.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Behçet’s disease (BD) is a systemic inflammatory disease of unknown origin that affects various parts of the body. In some patients, the prognosis of the disease appears to be altered by the involvement of the intestine (intestinal BD). In intestinal BD, deep ulcers develop in the gastrointestinal tract, typically in the ileocaecum. Intestinal lesions in patients with BD are much more common in countries in the Far East, especially Japan. The tissue damage occurring in patients with BD is believed to be caused by oxygen radicals, which are promoted by proinflammatory cytokines and arachidonic acid metabolites. New formulations of mesalazine (5-aminosalicylic acid; 5-ASA) are now available for the treatment of intestinal BD. Mesalazine breaks the chain reaction of free radical production. Mesalazine may provide an effective treatment for the promotion of long term healing of mucosal ulceration of the intestine in patients with BD.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Most of the drugs prescribed to treat acute gouty attacks were used before the introduction of modern clinical trials. Thus, there are few well-designed studies available to evaluate these drugs. Nevertheless, worldwide clinical experience supports the use of most nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids in the treatment of acute gout.Colchicine has been widely used but toxicity, especially gastrointestinal adverse effects, are a major concern. Therapeutic regimens involving hourly or 2-hourly administration were based on the short initial half-life of colchicine in plasma. Other therapy schedules, such as early 8-hourly administration, may be equally effective and have fewer adverse effects. Unfortunately, comparative studies to investigate this have not been performed. Colchicine should not be prescribed to patients with either severe renal insufficiency or combined hepatic-renal insufficiency. Doses should be halved in patients with moderate renal function impairment.NSAIDs are the most widely prescribed drugs in the treatment of acute gout. Few comparative data are available, but any of the most potent NSAIDs are probably useful in the control of pain and inflammatory signs of acute gouty arthritis. Pharmacokinetic properties should be taken into account when selecting an NSAID for the treatment of gout, as rapid absorption and a short half-life may help to avoid accumulation in patients with subclinical renal function impairment. Comorbidities should always be kept in mind when prescribing NSAIDs. Patients with previous or recent gastrointestinal bleeding, those receiving anticoagulant therapy or with haemorrhage diathesis, and those with renal insufficiency are at risk of developing severe adverse effects from NSAID administration.Corticosteroids are probably a reasonable choice for patients in whom colchicine and NSAIDs may be hazardous or for those with a history of previous intolerance to these drugs. Few trials using prednisone, prednisolone or triamcinolone acetonide are available, and dosages are prescribed following empirical data. Corticotropin has also been used to treat acute gout. Although it has been proven to be as effective as other corticosteroids or indomethacin, the need for multiple doses, parenteral administration and the high cost are major limitations for its use.Currently, the choice of a drug for the treatment of acute gout will depend on the balance between its efficacy and the potential adverse effects in a particular patient.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease leading to joint destruction. It is the most common cause of potentially treatable disabilities. The outcome of the disease varies from very mild to a refractory, rapidly progressive type with a high mortality rate. In recent years, profound changes in the traditional paradigms of RA therapy have been introduced. Instead of a therapeutically progressive approach, aggressive therapy is recommended for aggressive forms of RA. It has forced us to remodel the traditional treatment pyramid, and to start new strategies such as saw-tooth or step-down-bridge schedules. The last 10 years have seen wide acceptance of immunosuppressive therapy. These agents hold much promise for the further treatment of RA. A few years ago it seemed that we would be unable to influence the long term outcome in RA, but today the development of new drugs and techniques has increased our chances of fighting RA, and prospects for the future are even more promising.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Each year, approximately 210 000 American men are diagnosed with prostate cancer and 41 800 die from the disease − numbers roughly equal to the incidence and mortality for breast cancer in women. Prostate cancer usually shows no symptoms in early stages, when it is most treatable. To detect the disease early, physicians usually recommend that every man 50 years and older have an annual examination consisting of a digital rectal examination and a prostate specific antigen (PSA) blood test. Conventional treatments such as surgical removal of the diseased prostate, external beam radiation, radioactive seed therapy and hormonal and/or chemotherapy treatment regimens are most successful for early stage prostate cancer and have limited effectiveness in advanced stages of the disease. For this reason, accurate staging of primary and recurrent prostate cancer is mandatory for proper therapeutic decisions.Nuclear medicine imaging of prostate cancer using the radiolabelled monoclonal antibody,111In-capromab pendetide, has proven useful in newly diagnosed patients with biopsy-proven prostate cancer in which there is high suspicion of distant metastatic disease and for prostatectomy patients with rising PSA levels and/or suspicion of recurrence or metastatic disease. Although not intended as a screening tool, it is used in conjunction with standard evaluation procedures for improved staging of patients. The monoclonal antibody, designated 7E11-C5, binds the prostate specific membrane antigen (PSMA) expressed on the surface of prostate epithelial cells and up-regulated in tumour cells.The sensitivity and specificity for prostate cancer involved lymph node detection has been reported as 62 to 75% and 72 to 86%, respectively, compared with sensitivities of 4% and 15% for computerised tomography and magnetic resonance imaging.111In-capromab pendetide imaging has proven to be an accurate, non-invasive tool for detecting and staging sites of recurrence in the post-prostatectomy patient as well as metastatic sites in the patient with newly diagnosed prostate cancer.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS