Research progress of CYPA in malignant tumors / 国际生物医学工程杂志

Cyclosporin A (CYPA) is an important member of the cyclophilin family, encoded by the peptidyl prolyl isomerase A gene, and has a variety of important biological functions, mainly involved in inflammation, immunity, and other pathophysiological processes. In addition, CYPA plays a regulatory role in tumor cell proliferation, invasion, apoptosis, metastasis, angiogenesis, and epithelial-mesenchymal transition through various molecular mechanisms, among which the specific binding of CYPA to CD147 has received wide attention. In this review, the mechanism of CYPA in various malignant tumors was mainly reviewed, and its regulatory mechanism and potential interventions in malignant tumors were analyzed, with the aim that CYPA will play an important role in the early diagnosis and precise treatment of tumors in the future.

Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia / 中国医学科学院学报

Objective To compare the efficacy and safety of cyclosporin A(CsA)and CsA combined with recombined human erythropoietin(rhEPO)in the treatment of patients with chronic aplastic anemia(CAA).Methods Data of 79 patients with CAA treated at Department of Hematology,PUMC Hospital between January 2016 and June 2018 were collected for retrospective analysis.Forty-five patients were treated with CsA+rhEPO,and the other 34 patients with CsA alone.All the enrolled patients were treated for at least 1.5-2.0 years and followed for at least 1.0 year.The efficacy,side effects,long-term outcomes were compared between the two groups,and factors that may influence the efficacy were analyzed.Results The patients treated with CsA+rhEPO included 14 males and 31 females,with a median age of 43(19,73)years old.The median treatment duration of CsA and rhEPO was 26(12,38)and 4(3,6)months,respectively,and the median followed-up time was 24(12,42)months.The patients treated with CsA alone included 16 males and 18 females,with a median age of 36(16,85)years old.The median CsA treatment duration was 24(12,40)months and the median follow-up time was 25(12,40)months.There was no statistical difference in baseline characteristics between the two groups(all

Role of cyclophilin A during coronavirus replication and the antiviral activities of its inhibitors / 生物工程学报

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.

The protective effects of cyclosporin A on vascular permeability in sepsis rats / 药学学报

The protective effects of cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP), on vascular permeability in sepsis rats were investigated. Cecal ligation and puncture (CLP)-induced sepsis rats were used for in vivo studies, and the effects of CsA (1 and 5 mg·kg-1) on vascular permeability of lung, kidney, and intestine, mitochondrial respiratory control ratio, and the survival of the sepsis rats were observed. Lipopolysaccharide (LPS) was used for stimulating vascular endothelial cells (VECs) in vitro, and the effects of CsA on leakage of microvascular, immunofluorescence of zonula occludes-1 (ZO-1), and transendothelial electrical resistance (TER) were observed. All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of the Army Medical University. Compared with sham-operated group, the vascular permeability of lung, kidney, and intestine in sepsis rats increased significantly (P<0.05). Compared with conventional treatment group, CsA could significantly decrease the vascular permeability of lung, kidney, and intestine (P<0.05 or P<0.01), and prolong the survival period. The results of microcirculation also showed that CsA could significantly reduce the permeability of mesenteric venules in sepsis rats. At the cellular level, LPS stimulation significantly increased the permeability of vascular endothelial cells, including the decrease of transmembrane resistance and protein expression of ZO-1 (P<0.05). CsA can significantly reduce the increase of permeability of vascular endothelial cells induced by LPS stimulation (P<0.01). The function of mitochondria in the kidneys and intestines of sepsis rats was obviously impaired, and the respiratory control ratio of mitochondria was decreased. LPS significantly increased MPTP opening of VECs, while CsA significantly inhibited MPTP opening and improved mitochondrial function. CsA may protect mitochondrial function by inhibiting the opening of MPTP and play a protective role in the vascular permeability of sepsis rats. This study will provide an insight for the treatment of sepsis vascular leakage.

Effect of cyclosporine A combined with glucocorticoid in the treatment of corneal ulcer / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the effect of cyclosporine A combined with glucocorticoid in the treatment of corneal ulcer.<p>METHODS: From May 2015 to May 2018, 200 patients with corneal ulcer were selected and divided into combined group and glucocorticoid group according to different treatment methods, 100 cases each. In the combined group, cyclosporine A was given on the basis of the glucocorticoid group. C-reactive protein(CRP)and interleukin-6(IL-6)were measured to evaluate the quality of life, clinical symptoms, treatment efficiency, recurrence rate and incidence of adverse reactions.<p>RESULTS: After treatment, the levels of CRP and IL-6 in the two groups were lower than that before treatment, and the quality of life was higher than that before treatment(<i>P</i><0.05). The level of CRP and IL-6 in the combined group was lower than that in the glucocorticoid group, and the quality of life was higher than that in the glucocorticoid group(<i>P</i><0.05). The time of conjunctival hyperemia, ophthalmalgia and ulcer healing in the combined group were lower than those in the glucocorticoid group(<i>P</i><0.05). The effective rate of combined group was higher than that of glucocorticoid group, and the recurrence rate of combined group was lower than that of glucocorticoid group(<i>P</i><0.05).<p>CONCLUSION: Cyclosporine a combined with hormone is effective in the treatment of corneal ulcer, which can improve the clinical symptoms, reduce the inflammation, improve the quality of life and reduce the recurrence.

<i>In vitro</i> interactions between antifungals and Cyclosporin A against Fusarium solani / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the<i> in vitro</i> interaction between antifungals and tacrolimus acting alone or in combination against Fusarium solani.<p>METHODS: According to Clinical and Laboratory Standards Institute(CLSI)M27-Ed4 and M38-A3, 22 strains of Fusarium solani were used to perform drug sensitivity tests with chessboard microdilution method by cyclosporin A combined with 4 kinds of antifungal drugs <i>in vitro</i>.<p>RESULTS: The MIC ranges of natamycin, voriconazole, amphotericin B and fluconazole against 22 strains of Fusarium solani were 2-8, 1-8, 1-8 and 8-512μg/mL respectively. When combined with tacrolimus <i>in vitro</i>, the synergistic effects of fluconazole and Amphotericin B were observed in 64% and 41% strains respectively. There were no antagonistic effects observed in all combined drug tests. With the combination, the sensitivity of Fusarium to amphotericin B was significantly increased from 4.5% to 68.2%(<i>P</i><0.001).<p>CONCLUSION: Fusarium solani is sensitive to natamycin <i>in vitro</i> and is partially sensitive to voriconazole. When combined with cyclosporine A, it can produce synergistic effects with fluconazole and amphotericin B, and significantly increase the sensitivity of Fusarium solani to amphotericin B drugs.

Agrandamiento gingival generalizado en un paciente con trasplante renal / Generalized gingival enlargement in a patient with renal transplant

Introducción: El agrandamiento gingival es el aumento exagerado y desfigurante del volumen de la encía. Su aparición se asocia a fármacos, entre los que se encuentran los inmunosupresores y los bloqueadores de los canales de calcio como la ciclosporina A y amlodipino. Objetivo: Describir un caso clínico de agrandamiento gingival asociado a ciclosporina A y amlodipino, con periodontitis crónica subyacente, su tratamiento y prevención de recidiva. Presentación del caso: Paciente masculino, de 50 años de edad, antecedentes de hipertensión arterial, asma bronquial y hepatitis C, además de presentar insuficiencia renal crónica para la cual se le realizó un trasplante renal. Recibe tratamiento con ciclosporina A y amlodipino. Al examen clínico se observaron aumento de volumen generalizado en la encía, que cubría completamente la corona de los dientes, bolsas periodontales de 5 a 8 mm, sangramiento gingival y movilidad dentaria. Principales comentarios: El proceso diagnóstico permitió comprobar que además del agrandamiento gingival generalizado existía una periodontitis crónica generalizada. Conclusiones: La ingestión de un inmunosupresor como la ciclosporina A con el uso de un bloqueador de los canales de calcio, el amlodipino, y la influencia de factores de connotación local, parecen ser los responsables de la aparición combinada del agrandamiento gingival generalizado y la periodontitis crónica concomitante. La fase higiénica contribuyó considerablemente a mejorar el estado periodontal, cuya solución definitiva se alcanzó con la cirugía periodontal convencional. Se corrobora la importancia del examen periodontal en pacientes candidatos a trasplantes de órganos(AU)

Introduction: Gingival enlargement is an exaggerated and disfiguring increase in gum volume, associating its appearance with drugs like immunosuppressants and calcium channel's blockers such as cyclosporine A and Amlodipine. Objective: To describe a clinical case of gingival enlargement associated to cyclosporine A and amlodipine, presenting chronic underlying periodontitis, its treatment and prevention in case of recurrence. Case Presentation: Male patient, 50 years old with a history of arterial hypertension, bronchial asthma and hepatitis C, and presenting chronic renal failure leading renal transplant. The patient was treated with cyclosporine A and amlodipine. In the clinical examination was observed an increased volume in the gum, which completely covered the crown of the teeth, also periodontal bags of 5 to 8 mm, gingival bleeding and dental mobility. Main Comments: The diagnostic process allowed to verify that in addition to the generalized gingival enlargement there was a generalized chronic periodontitis. Conclusions: The ingestion of an immunosuppressant such as Cyclosporin A with the use of a calcium channel's blocker, amlodipine, and the influence of local connotation factors seem to be responsible for the combined appearance of generalized gingival enlargement and concomitant chronic periodontitis. The hygienic phase contributed considerably to improve the periodontal state, whose definitive solution was achieved with conventional periodontal surgery. The importance of periodontal examination in patients who are candidates for organ transplants is corroborated(AU)

Assessment of The Potential Role of Parsley (Petroselinum Crispum) Leaves Extract in Ameliorating Cyclosporin A- Induced Nephrotoxicity in Rats

In this study, a potentiometric titration method by Calvin-Bjerrum and Irwing-Rosotti was used to investigate binarycomplexes of ibandronate sodium, a nitrogen-containing bisphosphonate, with Ca(II), Mg(II) and Sr(II). Dissociationconstants (pKa) of ibandronate sodium were measured and the stability constants of the complexes formed in aqueoussolutions at 22 oC (I = 0.11 M NaClO4) were determined. The stoichiometry of ibandronate sodium/metal complexes wasfound as 1/1 for each metal ion.

Identification of the related substances of cyclosporin A by LC-MS techniques / 中国药科大学学报

@#To identify the related substances of cyclosporin A by LC-MS techniques, the separation of cyclosporin A and its related substances was carried out on a Hypersil BDS C18(100 mm×4. 6 mm, 2. 4 μm)column with isocratic elution by a mixture of acetonitrile-water-MTBE and formic acid(430 ∶520 ∶50 ∶1)as the mobile phase. Cyclosporin A and its 29 related substances(9 process related and 20 degradants)were well separated under the established conditions. Among them, 13 were listed in EP and the rest 16 were unknown products having not been reported before. Electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of parent ions of all the components, and triple quadrupoles tandem mass was employed for the product mass spectra determination. Thence, the structures of all the 29 detected substances were successfully characterized through spectra elucidation and the fragmentation pathways analysis. The established LC-MS method was successfully employed for the separation and identification of the related substances of cyclosporin A and it is useful for its fermentation processes and quality control.

Simvasatin plus cyclosporin A inhibits obliterative bronchiolitis in a murine heterotopic tracheal transplant model / 中华器官移植杂志

Objective@#To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model.@*Methods@#Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients. Transplanted animals received either control chow, chow containing simvastatin, chow containing cyclosporine A, or chow containing simvastatin and cyclosporine A. beginning immediately after transplantation. Epithelial loss and luminal obstruction were analyzed by morphometry. Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts. collagen deposition was studied by picro sirius red staining.Group t test was used to calculate the difference between groups.@*Results@#simvastatin combined with cyclosporin A treatment reduced chemokine(MCP-1, RANTES)release, inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts, resulting in limited bronchial inflammation and diminished epithelial loss. simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells, reduced MMP-2 release and decreased the amounts of type I and III collagen deposition, resulting in preserved luminal patency and inhibited development of OB compared with those of controls.@*Conclusions@#When simvastatin was used in combination with CsA, the development of OB was significantly inhibited.

Simvasatin plus cyclosporin A inhibits obliterative bronchiolitis in a murine heterotopic tracheal transplant model / 中华器官移植杂志

Objective To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model .Methods Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients .Transplanted animals received either control chow ,chow containing simvastatin ,chow containing cyclosporine A ,or chow containing simvastatin and cyclosporine A . beginning immediately after transplantation .Epithelial loss and luminal obstruction were analyzed by morphometry .Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts .collagen deposition was studied by picro sirius red staining .Group t test was used to calculate the difference between groups .Results simvastatin combined with cyclosporin A treatment reduced chemokine (MCP-1 , RANTES ) release , inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts ,resulting in limited bronchial inflammation and diminished epithelial loss .simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells ,reduced M M P-2 release and decreased the amounts of type I and III collagen deposition ,resulting in preserved luminal patency and inhibited development of OB compared with those of controls .Conclusions When simvastatin was used in combination with CsA ,the development of OB was significantly inhibited .

Performance Evaluation of the ARCHITECT i2000 for the Determination of Whole Blood Cyclosporin A and Tacrolimus / 임상검사와정도관리

Maintaining immunosuppressant concentrations within the therapeutic range in organ recipients requires regular monitoring. The blood concentrations of immunosuppressants are routinely measured using one of several automated immunoassays, such as chemiluminescence immunoassays (CLIAs) and liquid chromatography-tandem mass spectrometry (LC-TMS). The ARCHITECT i2000 immunoassay analyzer (Abbott Diagnostics, USA) was developed as an automated CLIA analyzer for the measurement of cyclosporin A and tacrolimus in whole blood. Here, the precision and linearity of the ARCHITECT i2000 analyzer for the detection of cyclosporin A and tacrolimus in whole blood were evaluated according to Clinical and Laboratory Standards Institute guidelines and were compared with those of an LC-TMS detection method. The total coefficient of variation for the two drugs was less than 10%, and they showed linearity values of 0.97 or more, which was within the manufacturer's range. The measurements of both immunosuppressants by the ARCHITECT i2000 were closely correlated with measurements determined by LC-TMS. However, most measurements were lower with LC-TMS than with the ARCHITECT i2000. Measurement of cyclosporin A and tacrolimus in whole blood using the ARCHITECT i2000 showed very satisfactory performance in terms of precision and linearity as well as good correlation with the comparative method.

Molecular Pathway of Psoralidin-Induced Apoptosis in HepG2 Cell Line / 中国结合医学杂志

OBJECTIVE@#To test the role of psoralidin in human liver cancer HepG2 cells in vitro.@*METHODS@#Cell viability was assessed by methylthiazolyldiphenyl-tetrazolum bromide assay and apoptotic cells were labeled by annexin V then sorted by flow cytometry. Protein expressions of caspase-3, caspase-8, caspase-9, Bax, Bid, Bcl-2, Bcl-xL and p53 were examined by western blot while activity of caspase-3, -8 and -9 were also determined.@*RESULTS@#Psoralidin reduces cell viability greatly in a time dependent manner (64%, 40%, 21%, 12% at 2, 6, 24 and 48 h treatment with 64 μmol/L psoralidin respectively) and up-regulates activities of caspase-3, -8 and -9 in a concentration dependent manner (between 4 to 64 μmol/L). Psoralidin also increases the expression of pro-apoptosis genes Bax, Bid and p53 while decreases the expression of pro-survival genes Bcl-2 and Bcl-xL, both in a concentration dependent manner between 4 and 64 μmol/L (P<0.05 at 16 and 64 μmol/L). Caspase-3 inhibitor (Ac-DEVD-CHO at concentrations between 10 to 20 μmol/L), p53 inhibitor (pifithrin-α at 5 μmol/L) and cyclosporin A can attenuate the apoptotic effect of psoralidin.@*CONCLUSION@#The cytotoxic role of psoralidin might work through both intrinsic and extrinsic apoptotic pathway.

The protective effect of Xuebijing on mouse model of immunosuppressed sepsis / 天津医药

@#Objective To observe the effect of Xuebijing on immunosuppressed sepsis of model mice. Methods The 152 mice were randomly divided into control group (Control), immunosuppression group (IM), immunosuppressed sepsis model group (ISM) and Xuebijing treatment group (XT). There were thirty – eight mice for each group. For group IM, cyclosporine A was injected intraperitoneally along the median line of the lower abdomen for immunosuppression, 25 mg/kg， 1 time every other day for a total of 3 times. For group ISM, after immunosuppression, 300 μL escherichia coli 44102 with a concentration of 1×109 CFU/mL was injected intraperitoneally along the midline of the lower abdomen. The 30 minutes after the establishment of the immunosuppressive sepsis model, Xuebijing 4 mL/kg was intraperitoneally injected along the midline of the lower abdomen in the ISM group. After 30 minutes, the same dose of Xuebijing injection was repeated once. Control group was injected intraperitoneally with the same amount of normal saline. (1) After 8 h, 4 mice in each group were taken for blood bacterial culture. (2) After 12 h, 10 mice in each group were taken for detecting CD3+CD4+ and CD3+CD8+ in peripheral blood using flow cytometry. (3) After 12 h, 10 mice in each group were taken for detecting blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). (4) After 12 h, 4 mice in each group were taken for detecting high-mobility group protein (HMGB1) by Western blot assay. (5) After 12 h, 10 mice in each group were taken for detecting alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and serum creatinine (CR) levels by automatic biochemical analyzer. Results Compared with the ISM group, the ratio of CD3+CD4+/CD3+CD8+ was significantly increased, the number of blood bacteria culture decreased obviously in the XT group. Liver and kidney function indicators ALT, AST, CR, BUN and inflammatory factor indicators TNF-α, IL-6 and HMGB1 were also significantly decreased in the XT group. Conclusion Xuebijing can obviously modulate the immunosuppression, against bacteria, inhibit the inflammatory reaction, and protect the vital organs.

Pharmaceutical Care of Hypertension Induced by the Combination of Cyclosporine A and Voriconazole in A Child with Aplastic Anemia / 医药导报

Objective To investigate the pharmacy practice of clinical pharmacists' attendance in the treatment of adverse reactions caused by drug interactions. Methods Analysis was conducted on the causes and treatment of hypertension in one pedinatric patient with aplastic anemia induced by combined use of cyclosporine and voriconazole. Results Cyclosporine A could lead to prolonged hypertension.Cyclosporine A dosage should be adjusted;antihypertensive drugs should be used in necessity.When choosing antihypertensive drugs,drug interaction with cyclosporine A should be considered. Conclusion Clinical pharmacists could manage adverse drug reactions by analyzing drug interactions,and offer suggestions for ADR patients.

The application of HPLC-MS/MS method in the determination of whole blood concentration of Cyclosporine A and AM1 in bone marrow transplant patient / 重庆医学

Objective To develop a HPLC-MS/MS methodfor determination of cyclosporin A(CSA)and AM1 in bone marrow transplant patient,and explore the relationship of CSA and its main metabolite AM1 within individual and between individuals,and provide reliable basis for clinical rational use of monitoring in CSA blood drug concentration.Methods CSD was used as internal standard,and whole blood samples were treated with internal standard methanol precipitated protein.The column was Ultimate XB-C18 with a column temperature of 65 ℃ and the mobile phase was eluted with 0.1％ of formic acid and 2 mmol/L ammonium acetate in water and methanol containing 0.1％ formic acid.The mass spectrometry was detected by electrospray ion trap positive ion mode,MRM scanning,monitoring CSA 1219.9 to 1203.1 m/z,AM1 1236.1 to 1219.1 m/z,CSD 1234.0 to 1217.0 m/z.Results The concentration of CSA was linear in the range of 16 to 1600 ng/mL,Y=0.0143X+0.0213(r=0.9976).The concentration of AM1 was linear in the range of 10～1000 ng/mL,Y=0.00363X-0.00528(r=0.9973).The ratio of CSA to AM1 (AM1/CSA) between individual ranged from 32％ to 356％.The ratio of CSA to AM1 within indiviolual(AM1/CSA) ranged from 27 ％ to 147 ％.Conclusion HPLC-MS/MS method for the simultaneous detection of CSA and AM1 was established.The variation of CSA exists in the bone marrow transplant patient between individuals and within individual;the HPLC-MS/MS method can be used for monitoring of whole blood concentration of CSA in bone marrow transplant patients.

Correlation between Liver and Kidney Toxicity and Cyclosporin A Blood Concentration in 1236 Samples of Patients with Aplastic Anemia / 中国药师

Objective:To analyze the correlation between cyclosporin A blood concentration and drug-induced liver and kidney in-jury in the patients with aplastic anemia, investigate the significance of cyclosporin A concentration in the monitoring of liver and kidney toxicity, and provide theoretical basis for clinical individualized drug use. Methods:A total of 149 patients with aplastic anemia trea-ted with cyclosporin A as the main therapeutic drug were selected, and after 3-day treatment, the blood concentration of cyclosporin A was detected by an HPLC-UV method 10 minutes before the administration and 2 hours after the administration. The liver and kidney function were measured at the same time. The correlation between the different concentration of cyclosporine A and the change of liver and kidney function was analyzed. Results:All the patients were monitored cyclosporine A blood concentration with 1236 samples, and 34 patients (22. 82%) were with drug-induced liver injury and 51 patients (34. 23%) showed drug-induced kidney toxicity. The average C0 of liver injury patients was (297. 92 ± 74. 14) μg·L-1 , and C2 was (944. 47 ± 148. 47) μg·L-1 , while the average C0 of kidney injury patients was (311. 41 ± 52. 80)μg·L-1, and C2 was (926. 25 ± 136. 02) μg·L-1. The function indices of liver (ALT, AST, TBIL) and kidney (SC, BUN, UA) were significantly higher than those in the normal group (P<0. 05), and the blood concentration of cyclosporin A was significantly correlated with the liver,and kidney function. Conclusion:There is a certain correla-tion between cyclosporine A -induced toxicity and its blood concentration and C2 may be a more valuable predictor for drug -induced liver injury.

Intra-articular Xenotransplantation of Adipose-Derived Stromal Cells to Treat Osteoarthritis in a Goat Model

Adipose-derived stromal cells (ASCs) have been investigated as a cell source for tissue regeneration. The purpose of this study was first to confirm if medial meniscectomy induces osteoarthritis (OA) in goats within a relative short period of time, and more importantly, to investigate if systemic treatment with immunosuppressive drugs is necessary in intra-articular ASC xenotransplantation for successful regeneration of articular cartilage and prevention of joint inflammation. Eight Korean native black goats 1–2 years of age underwent medial meniscectomy. To evaluate the gross and histological appearance of articular cartilage, knee joints were re-exposed by a medial parapatellar incision at 8 weeks. After macroscopic scoring of gross appearance, cartilage biopsy specimens 6 mm in diameter were obtained from the femoral condyle in four goats. The goats were injected with single intra-articular dose of 7×10₆ human ASCs (hASCs) 7 days after the second arthrotomy. Four animals were treated with daily injections of cyclosporin A 10 mg/kg for 7 days, followed by a reduced dose of 5 mg/kg for another 7 days, while other 4 animals did not receive immunosuppressive therapy. All animals were sacrificed for analysis 8 weeks after injection of hASCs. OA was successfully induced 8 weeks after medial meniscectomy. Eight weeks after injection of hASCs, various signs of articular cartilage regeneration were observed. There were no significant macroscopic and histological differences between goats treated with cyclosporine and untreated goats. Interleukin-1β and tumor necrosis factor-α level from synovial fluid did not differ between cyclosporine-treated and untreated goats. The results indicate that immunosuppressive therapy did not influence the result of ASC xenotransplantation to treat OA.

Effect of acute and chronic treatment of Cyclosporin A on liver and kidney functions in rats.

Cyclosporin A is a compound widely used as an immunosuppressive drug, particularly, in case of kidney transplantation to prevent rejection of transplanted organ. This study aimed to investigate the bad side effect of acute and chronic treatment with cyclosporin A on liver and kidneys by measuring liver enzymes and kidney function tests in serum. Male rats were used as experimental model in this study. The results of this study concluded that, chronic treatment with cycloosprin A leads to increase in serum urea, creatinine, and uric acid significantly compared to control, also, ALT and Alkaline phosphatase activities in serum were increased by chronic administration of cyclosporine A for four weeks. Decrease of serum albumin and total protein were observed significantly compared to control groups.

Establishment of an allogenetic skin transplant model in mice for evaluating immunosuppressive drugs / 中国药理学通报

Aim To establish an allogenetic mouse skin trans-plant model,in order to provide a research model for immunosup-pressive drugs. Methods Skins from the ears of C57BL/6 mice were transplanted to the back of BALB/c mice and skin isografts ( BALB/c mice to BALB/c mice) were used as control. Cyclos-porin A( CsA) was used as a model compound to test the imm-nosuppresive effect on allogenetic graft rejection. Following the transplation and CsA treatment, the graft rejection score and graft skin survival rate were quantified. Four and nine days after transplantation,serum IL-4,IL-12 and IFN-γ levels were meas-ured using ELISA kits. Twelve days after transplantation, mice were sacrificed. The weight of spleen and thymus was obtained, and CD4 + and CD8 + population of spleenic T cells were ana-lyzed using flow cytometer. Histological features were assessed by hematoxylin-eosin( HE) staining of formalin-fixed, paraffin-em-bedded graft skins. Results After transplantion, the graft rejec-tion score increased and graft skin survival rate decreased gradu-allly. Serum IL-12 and IFN-γ levels of allograft mice increased markedly. Compared with those of isograft mice, mice with skin allograft displayed a significant increase in the percentage of the CD8 + T cell subpopulation. Remarkable inflammation, such as edema, inflammatory cell infiltration were observed in allograft mice. Compared with saline treated mice, CsA significantly re-duced the graft rejection score and improved survival rate of skin grafts. And also, CsA treated mice had smaller spleen and thy-mus. Mice that received high doses of CsA had significantly less CD8 + T cells than those treated with saline. Moreover, allograft skins in mice that received CsA had less inflammation. Conclu-sions Allogenetic mouse skin transplantation exhibits acute graft rejection. CsA can inhibit the rejection in a dose dependent manner.