Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Humans ; Immunosuppressive Agents ; pharmacology ; Tripterygium ; adverse effects ; chemistry

Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete Nocardia brasiliensis IFM 0406 with highly potent immunosuppressive activity (IC₅₀=0.057 μg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.
Animals ; Mice ; Humans ; Immunosuppressive Agents/chemistry* ; Aminoglycosides/pharmacology* ; Cyclosporine/pharmacology* ; Diterpenes

OBJECTIVETo detect the factors relevant to stenosis of tracheal graft and to find feasible methods to solve this problem.

METHODSSixteen mongrel dogs were divided into groups A and B randomly and equally. Five-ring-length tracheal segments were allotransplanted. All grafts and anastomotic sites were covered with omental pedicles. In group A, no immunosuppressant was given and in group B, the recipients were treated with cyclosporine. The animals were sacrificed 4 weeks after operation, and their postmortem specimens were examined grossly and histologically. All allografts were assessed by percent patency. Epithelial regeneration and morphology of the cartilage were semiquantitatively evaluated.

RESULTSStructural integrity of the allografts were maintained better in group B than in group A. Tracheal stenosis was found to be more serious in group A. The scores of epithelial regeneration and cartilage morphology were higher in group B than in group A, and in each group positive correlation was found between the percent patency and the score of epithelial regeneration or cartilage morphology.

CONCLUSIONSImmunosuppressive drugs are necessary to maintain the structure of allografts. Tracheal stenosis is correlated closely with epithelial regeneration and morphological maintenance of the cartilage.

Animals ; Dogs ; Immunosuppressive Agents ; pharmacology ; Male ; Trachea ; pathology ; transplantation ; Transplantation, Homologous

OBJECTIVETo observe the effects of lipopolysaccharides of Bacterium prodigiosum (BP-LPS) in inhibiting tumor growth and improving immunosuppression in mice.

METHODSIn mice bearing S180 tumor and a mouse model of immunosuppression induced by cyclophosphamide (CTX), the tumor growth, indexes of the immune organs and peripheral white blood cell count were measured after intraperitoneal injection of BP-LPS.

RESULTSInjections of BP-LPS (40 U/kg) for 8 consecutive days resulted in a significant inhibition of the tumor growth in mice bearing S180 tumor (P<0.01), with a dose-dependent increase of the spleen indexes but no obvious changes in the thymus indexes. Intraperitoneal injections of BP-LPS for 7 days inhibited the reduction of peripheral white blood cells and spleen indexes in immunosuppressive mice, but did not produce any significant changes in normal mice.

CONCLUSIONBP-LPS can inhibit the tumor growth in tumor-bearing mice and enhance the immune functions of immunosuppressive mice.

Animals ; Antineoplastic Agents ; pharmacology ; Female ; Immunosuppressive Agents ; pharmacology ; Lipopolysaccharides ; isolation & purification ; pharmacology ; Male ; Mice ; Polysaccharides, Bacterial ; isolation & purification ; pharmacology ; Random Allocation ; Serratia ; chemistry

To further understand triptolide, this paper has introduced the pharmacology, pharmacokinetics, toxicity, the clinic application and semi-synthesis of triptolide on basis of importance and significant contents of reference which have been consulted in the past twenty years. Presently triptolide and Tripterygium wilfordii have been a hot spot of modernization of Chinese traditional medicine. It is very important to develop a new dosage form of high effect and low toxicity by making use of advanced technology according to its characteristics.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antineoplastic Agents, Alkylating ; pharmacology ; Antispermatogenic Agents ; pharmacology ; Diterpenes ; chemical synthesis ; isolation & purification ; pharmacology ; toxicity ; Epoxy Compounds ; Humans ; Immunosuppressive Agents ; pharmacology ; Phenanthrenes ; isolation & purification ; pharmacology ; toxicity ; Tripterygium ; chemistry

In the past 50 years, organ transplantation has developed from an improbable laboratory exercise to a major therapeutic success. The surgical problems of organ grafting have, for the most part, been solved. Rejection of grafts is now partially understood and usually controllable by powerful immunosuppressive drugs. A steady improvement in patient outcome, especially following the introduction of cyclosporin as an immunosuppressive agent has resulted in a worldwide shortage of organs for transplantation. This has provoked serious ethical dilemmas in every country. These matters are summarised in the following text.
Biomedical Research ; Cyclosporine ; pharmacology ; Graft Rejection ; drug therapy ; prevention & control ; Humans ; Immunosuppression ; Immunosuppressive Agents ; pharmacology ; Transplants ; ethics

No abstract available.
Animals ; Cyclophosphamide/*pharmacology ; Immunosuppressive Agents/*pharmacology ; Lung/*drug effects ; Lung Injury/*drug therapy ; Male ; *Paraquat ; Pulmonary Edema/*drug therapy

Calcineurin inhibitors (CNI), including oral cyclosporin A and tacrolimus, are intensive immunosuppressants that are extensively used in the treatment of rheumatic and immunologic diseases in China. CNI selectively inhibit the activation and proliferation of T lymphocytes and the transcription of cytokines [such as tumor necrosis factor-α, interleukin (IL)-6, and IL-17] through inhibiting the activation of calcineurin in cells and reducing the release of IL-2. To standardize the use of CNI in the field of rheumatic and immunologic diseases, this consensus statement was developed by the National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), in conjunction with the Chinese Association of Rheumatology and Immunology Physicians, the Chinese Research Hospital Association, the Rheumatology and Immunology Professional Committee, and the Chinese Association of Rehabilitation Medicine. The 2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence was used to rate the quality of the evidence and the strength of the recommendations, and the RIGHT (Reporting Items for practice Guidelines in HealThcare) checklist was followed to report the consensus. The consensus offers recommendations addressing nine clinical challenges to Chinese clinicians. The primary objective of this consensus is to deliver scientific and detailed guidance on CNI for Chinese clinicians, and to improve the quality of patient-centered medical services.
Humans ; Calcineurin Inhibitors/pharmacology* ; Immunosuppressive Agents/therapeutic use* ; Tacrolimus/pharmacology* ; T-Lymphocytes ; Immune System Diseases ; Rheumatic Diseases/drug therapy*

Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Humans ; Immunosuppressive Agents ; pharmacology ; Research Design ; Tripterygium ; adverse effects ; chemistry

OBJECTIVETo review kidney transplantation in the center and analyze the risk factors affecting long-term allograft survival.

METHODSThirty-two relative variables were analyzed with SAS statistical software. Using Log-rank method, we investigated influence of these variables on short-and long-term survival of grafts. Kaplan-Meier analysis was used to estimate the 1-, 3-, 5-, 10-years graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess and rank the relative risk of potential variables.

RESULTSThe 1-, 3-, 5-, 10-years graft survival rates were 83%, 75%, 66% and 48%. After excluding the patients died with functioning grafts, the 1-, 3-, 5-, 10 years grafts survival rate increased to 89%, 82%, 75% and 69%, respectively. The mean half-life was 8.78 +/- 0.14 and 14.09 +/- 0.20 years, respectively. By Log-rank analysis, factors affecting short- and long-term graft survival were identified as: renal function, duration of graft function became normal, cold-ischemia time, presence of acute rejection, delayed graft function, immunosuppressive regimen, complication, infection, anti-rejection therapy. Cox model multivariate analysis showed that there were 18 factors affecting graft survival.

CONCLUSIONSNew immunosuppressive agents not only significantly increase short-term graft survival, but also have the better long-term outcome tendency. Making assurance to get high quality donor organ and minimizing the death with graft function may be the most feasible way to prolong graft survival at present.

Adult ; Cadaver ; Female ; Graft Survival ; drug effects ; Humans ; Immunosuppressive Agents ; pharmacology ; Kidney Transplantation ; Male ; Multivariate Analysis ; Transplantation, Homologous