3.Effects of different immunodepressants on the sperm parameters of kidney transplant recipients.
Zheng-Guo CAO ; Ji-Hong LIU ; Yu-Ping ZHU ; Si-Wei ZHOU ; Ling QI ; Xiao-Cheng DONG ; Bin WU ; Zheng-Bin LIN
National Journal of Andrology 2006;12(5):405-407
OBJECTIVETo study the effects of different immunodepressants on the sperm parameters of kidney transplant recipients.
METHODSIn 15 healthy fertile men and 37 kidney transplant recipients, ejaculates were aseptically obtained by masturbation. Thirty-seven patients were divided into two groups, 20 patients were treated with Prograf (FK506) combination with mycophenolate mofetil (MMF) and prednisone; 17 patients were treated with cyclosporine (CsA) combination with azathioprine with prednisone. The sperm viability, mobility parameters such as prorsad percentage motility, straight line velocity (VSL), curve line velocity (VCL), velocity of average path (VAP) and morph were estimated with a computer-assisted sperm analyzer (CASA) provided with a multiple-exposure photography system.
RESULTSThere were no significant difference in sperm viability rate [(81.7 +/- 5.7)%, (79.4 +/- 6.8)% and (83.8 +/- 6.0)%], VCL [(24.1 +/- 8.6)%, (23.9 +/- 4.4)%, (24.8 +/- 4.2)% ] and VAP [(19.7 +/- 6.6)%, (18.6 +/- 2.9)%, (21.0 +/- 4.0)%] among groups of FK506, CsA and control, respectively (P > 0.05). The rate of anomaly [(67.8 +/- 5.7)%], the prorsad percentage motility [(46.4 +/- 8.1)%] and VSL [(15.4 +/- 4.6)%] in the group of FK506 were respectively significantly lower and higher than those in the group of CsA [(80.1 +/- 5.6%, (33.3 +/- 6.4)%, (10.2 +/- 2.4)%] (P < 0.05).
CONCLUSIONThe application of FK506 combined with MMF could help recover the mobility and morphology of the sperm in kidney transplantation recipients.
Adolescent ; Adult ; Case-Control Studies ; Cyclosporine ; pharmacology ; Drug Therapy, Combination ; Humans ; Immunosuppressive Agents ; pharmacology ; Kidney Transplantation ; Male ; Mycophenolic Acid ; analogs & derivatives ; pharmacology ; Prednisone ; pharmacology ; Sperm Motility ; drug effects ; Tacrolimus ; pharmacology
4.Effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD(34+) hematopoietic cells in bone marrow of asthmatic mice.
Hui MAO ; Kai-Sheng YIN ; Zeng-Li WANG ; Fu-Yu LI ; Xi-Long ZHANG ; Chun-Tao LIU ; Song LEI
Chinese Medical Journal 2004;117(4):592-597
BACKGROUNDCorticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the production of bone marrow inflammatory cells in asthma. This study observed the effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34+ hematopoietic cells, so as to explore the possible effectiveness of a bone marrow-targeted anti-inflammatory strategy.
METHODSBalb/c mice were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. For two consecutive weeks, asthmatic mice were challenged with OVA while being given either prednisone, montelukast, prednisone plus montelukast, or sterile saline solution. The mice were killed 24 hours after the last challenge with OVA, and bronchoalveolar lavage fluid (BALF), peripheral blood, and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cells in BALF, peripheral blood, and bone marrow were counted. The percentages of CD34+ cells, CD4+ T lymphocytes and CD8+ T lymphocytes among nucleated cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect expression of CD34 and interleukin (IL)-5Ralpha mRNA (CD34+ IL-5Ralpha mRNA+ cells) among bone marrow hematopoietic cells.
RESULTSCompared with the sterile saline solution group, the number of eosinophils in BALF and peripheral blood, CD34+ cells in peripheral blood and bone marrow, and CD34+ IL-5Ralpha mRNA+ cells in bone marrow of mice from the prednisone and prednisone plus montelukast groups were significantly lower (P < 0.01). The number of eosinophils in BALF from the montelukast group was also significantly lower (P < 0.05).
CONCLUSIONSThe results suggest that, in this asthmatic mouse model, prednisone probably inhibits proliferation, differentiation, and migration of CD34+ cells in bone marrow, blocks eosinophilopoiesis in bone marrow, and interferes with eosinophil migration into peripheral blood and subsequent recruitment in the airway. In addition, montelukast may suppress eosinophil infiltration into the lungs of asthmatic mice. However, a significant inhibitory effect of montelukast on the proliferation and migration of CD34+ cells and a cooperating effect with prednisone on bone marrow of asthmatic mice were not observed.
Acetates ; pharmacology ; Animals ; Antigens, CD34 ; analysis ; Asthma ; drug therapy ; Cell Count ; Hematopoietic Stem Cells ; drug effects ; Immunohistochemistry ; In Situ Hybridization ; Interleukin-5 ; biosynthesis ; Male ; Mice ; Mice, Inbred BALB C ; Prednisone ; pharmacology ; Quinolines ; pharmacology
5.Effect of modified sijunzi decoction on the bone metabolism of adriamycin induced nephropathy rats.
Jing ZHENG ; Jia-Lin LIU ; Min-Fang LIN ; Zhen-Fei WANG ; Ci-Yun LIU ; Xin-Hong WU ; Hua-Yang LIN ; Cai-Feng CHEN ; Xue-Min ZHENG ; Xiao-Ying CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2013;33(10):1376-1381
OBJECTIVETo explore the effect of Modified Sijunzi Decoction (MSD) on the bone metabolism of prednisone intervened adriamycin-induced nephropathy rats.
METHODSThe adriamycin-induced nephropathy rat model was prepared. Totally 50 SD rats were randomly divide into five groups, i.e., the model group, the hormone group, the Chinese medicine (CM) group, the CM + hormone group, and the normal control group. The 24-h urine samples were collected on the 7th, 21st, and 35th day after modeling. The 24-h urine protein was measured by biuret colorimetry. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), osteocalcin (BGP), and tartrate-resistant acid phosphatase (TRACP) were determined by ELISA. Expressions of OPG and RANKL in the tibia tissue were detected using real-time quantitative PCR and Western blot.
RESULTS(1) Compared with the normal control group, the 24-h urine protein increased in each group on the 7th, 21st, and 35th day (P < 0.05, P < 0.01). Compared with the model group, the 24-h urinary protein decreased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). The decrement was more obvious along with the treatment time went by (P < 0.05, P < 0.01). There was statistical difference in the reduction of urine protein on the 35th day between the CM group and the model group (P < 0.05). (2) Compared with the 21st-day of the same group, the serum levels of TRACP and RANKL increased (P < 0.05, P < 0.01). Compared with the model group, the serum levels of the TRACP and RANKL increased (P < 0.05, P < 0.01), OPG and BGP decreased (P < 0.05, P < 0.01) in the hormone group. Compared with the CM group at the same period, serum OPG level decreased and the RANKL level increased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). Besides, the serum level of TRACP increased and BGP decreased (P < 0.05, P < 0.01). Compared with the hormone group at the same period, OPG and BGP increased (P < 0.05, P < 0.01), RANKL decreased (P < 0.01) in the CM + hormone group. On the 35th day TRACP decreased (P < 0.01). (3) Compared with the normal group, mRNA expressions of OPG and RANKL on the 21st day increased (P < 0.05, P < 0.01), mRNA expressions of OPG and RANKL on the 35th day decreased in the model group (P < 0.01). Compared with the CM group at the same period, OPG mRNA expression decreased (P < 0.01) and RANKL mRNA expression increased in the hormone group (P < 0.05). OPG mRNA expression decreased in the CM +hormone group (P < 0.05). (4) Compared with the hormone group on the 21st day, the OPG level decreased and the RANKL protein increased (both P < 0.05). RANKL decreased in the CM + hormone group (P < 0.05). Compared with the model group at the same period, OPG decreased and RANKL increased in the hormone group (P < 0.01). Compared with the CM group at the same period, OPG decreased (P < 0.01), RANKL increased (P < 0.01) in the hormone group and the CM + hormone group. Compared with the hormone group at the same period, OPG increased and RANKL decreased in the CM + hormone group (both P < 0.01).
CONCLUSIONSPrednisone could induce osteoporosis through the OPG/RANKL/RANK pathway. MSZ could slow down the formation of prednisone-induced osteoporosis through promoting osteoblast differentiation, and inhibiting osteoclastogenesis.
Acid Phosphatase ; metabolism ; Animals ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Isoenzymes ; metabolism ; Male ; Nephrosis ; chemically induced ; metabolism ; Osteocalcin ; metabolism ; Osteoprotegerin ; metabolism ; Prednisone ; pharmacology ; RANK Ligand ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tartrate-Resistant Acid Phosphatase ; Tibia ; metabolism
6.Relationship between glomerular nephrin expression and oxidative stress reaction in rats with adriamycin-induced nephrosis.
Chinese Journal of Contemporary Pediatrics 2009;11(1):56-60
OBJECTIVEIt has been proposed that nephrotic syndrome is a consequence of an imbalance between oxidant and anti-oxidant activity. Nephrin plays an important role in maintaining glomerular filtration barrier. This study aimed to explore the relationship between the expression of glomerular nephrin and oxidative stress reaction in rats with adriamycin (ADR)-induced nephrosis, and the protection of prednisone and vitamin E against renal injuries.
METHODSNephrosis was induced by single intravenous injection of ADR (5 mg/kg). The prednisone intervention group was administered with prednisone (10 mg/kg daily) between 1 and 4 weeks after ADR injection. The vitamin E intervention group received vitamin E of 20 mg/kg daily from 1 week before ADR injection till to 4 weeks after ADR injection. Control rats were intravenously injected with normal saline. After 7, 14, 21 and 28 days of ADR injection, the indexes of oxidative stress reaction of the renal cortex, malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidative capacity (T-AOC), were measured using the chemical chromatometry. The protein expression of glomerular nephrin was measured by immunohistochemistry.
RESULTSPrednisone or vitamin E treatment reduced urinary protein from 14 days to 28 days after ADR injection. MDA levels of renal cortex increased, while renal activities of SOD and T-AOC as well as nephrin protein contents decreased in untreated nephrosis group from 7 days after ADR injection compared with those in the control rats. Compared with the untreated nephrosis group, prednisone treatment resulted in an increase in nephrin protein contents 28 days after ADR injection; Vitamin E treatment decreased renal MDA levels and increased renal activities of SOD and T-AOC and nephrin protein contents 28 days after ADR injection. Nephrin staining showed a sable linear-like pattern along the capillary loops of glomerulus in the control rats. Nephrin staining presented a light tan discontinuous short linear-like or punctiform pattern along the capillary loops of glomerulus in the untreated ADR group. Prednisone or vitamin E treatment ameliorated abnormal expression of nephrin induced by nephrosis. Glomerular nephrin expression level was negatively correlated with renal MDA level and positively correlated with renal activities of SOD and T-AOC.
CONCLUSIONSA reduction of glomerular nephrin expression is closely related to oxidative stress reaction. Prednisone and vitamin E have protective effects against renal injuries induced by ADR in rats.
Animals ; Doxorubicin ; toxicity ; Kidney Glomerulus ; metabolism ; Male ; Malondialdehyde ; analysis ; Membrane Proteins ; analysis ; Nephrosis ; chemically induced ; metabolism ; prevention & control ; Oxidative Stress ; Prednisone ; pharmacology ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Vitamin E ; pharmacology
7.Effects of qingyang toujie mixture in combination with prednisone tablet on Th1/Th2 cytokines in patients suffering from systemic lupus erythematosus.
Gang-Hua HUANG ; Yin-Huan CHEN ; Honq-Yan DUAN ; Ye LIU ; Xue-Fen LINAG ; Yu-Ping HE ; Xiao-Min WEN ; Qiu-Ying XU ; Zheng-Lun ZENG ; Jia-Xi ZHONG
Chinese Journal of Integrated Traditional and Western Medicine 2013;33(2):172-176
OBJECTIVETo research the effects of Qingyang Toujie Mixture (QTM) in combination with prednisone tablet on the balance of Th1 and Th2 (Th1/Th2) of systemic lupus erythematosus (SLE) patients of yin deficiency syndrome (YDS).
METHODSTotally 42 patients with SLE were recruited from clinics of internal medicine and hospitalization department of First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine from August 2009 to March 2011. They were randomly assigned to the treatment group (22 cases) and the control group (20 cases) according to the random digit table. Another 12 healthy subjects were recruited as the healthy control group from employees of First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine and healthy students in physical examinations. All patients took prednisone tablet. The dosage was adjusted according to the severity of SLE activity index and the condition: 40 -60 mg per day for severe active stage; 20-40 mg per day for moderate active stage; 15 -20 mg per day for light active stage; and less than 15 mg per day for those in the stable stage, respectively. When patients' condition had been stabilized for 1 to 2 weeks, the dosage was gradually reduced according to the method of hormone reduction. In case of the recurrence of symptoms or when complicated with lupus nephritis or lupus encephalitis uncontrollable, standard shock therapy with Cyclophosphamide Injection (0.5-1 g/m2 body surface area, intravenous dripping, once every 4 weeks) was performed. Patients in the treatment group took QTM additionally, one dose daily, taken in two portions, once in the morning and once in the evening. Those in the control group took placebos additionally, one dose daily, taken in two portions, once in the morning and once in the evening. The therapeutic course was 6 months for all. No measure was taken for those in the healthy control group. Venous blood was withdrawal before and after treatment. Th1 cytokines (IFN-gamma, IL-12) and Th2 cytokines (IL-10, IL-4) were detected by ELISA.
RESULTSCompared with the healthy control group, the serum Th1 cytokines such as IL-12 and IFN-gamma, Th2 cytokines such as IL-10 and IL-4 increased, the Th1/Th2 ratios such as IFN-gamma/IL-4 and IL-12/IL-10 decreased in the treatment group and the control group before treatment (P < 0.01). Compared with before treatment in the same group, the serum Th1 cytokines such as IL-12 and IFN-gamma decreased, the serum Th2 cytokines such as IL-10 and IL-4 decreased, the ratios of Th1/Th2 cytokines such as IFN-gamma/IL-4 and IL-12/IL-10 increased in the treatment group (all P < 0.05). Compared with the control group after treatment, IL-4 decreased, and the ratio of IFN-gamma/IL-4 increased in the treatment group (P < 0.05). Fewer patients suffered from adverse reactions in the treatment group than in the control group (P < 0.01).
CONCLUSIONQTM in combination with prednisone tablet was effective to improve the balance of Th1/Th2 cytokines, and alleviate the toxic and adverse reactions of hormone or immune inhibitors.
Adult ; Cytokines ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Humans ; Lupus Erythematosus, Systemic ; drug therapy ; immunology ; Male ; Prednisone ; administration & dosage ; pharmacology ; therapeutic use ; Th1-Th2 Balance ; drug effects ; Young Adult
8.Effects of triptolide on hypothalamic-pituitary-adrenal axis of rats.
Jian-hua ZHU ; Yong-liang HU ; Wu ZHANG ; Wei GUAN ; Guang-zhao HUANG
Journal of Forensic Medicine 2010;26(4):260-265
OBJECTIVE:
To observe the effects of triptolide on the hypothalamic-pituitary-adrenal axis (HPAA) of rats in light of morphological and functional changes.
METHODS:
Thirty Sprague-Dawley (SD) male rats were randomized into 3 groups and given 2% propylene glycol, mixture of propylene glycol and prednisone acetate or compounds of propylene glycol and triptolide by gavage, respectively, for consecutive 7 weeks. Determination in the 3 groups was conducted concerning the contents of blood plasma cortisol (COR), adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) besides measurement of the rats' body weight, coefficient of the adrenal gland and observation of the histopathological changes in fascicular zone of adrenal cortex. Immunohistochemical staining technique was used to detect the expression of ACTH in pituitary in the 3 groups.
RESULTS:
(1) The content of COR in the groups of triptolide and prednisone acetate appeared lower and serum ACTH showed no significant difference, but CRH in the group of triptolide was augmented as compared with the control group (P < 0.05). (2) The rats' weight in the groups of triptolide and prednisone acetate was declined, and yet, the coefficient of the adrenal gland remained no significant change in comparison with the controls. HE staining and electron microscopy examination revealed thinned and constricted zona fasciculata in adrenal gland in the rats of triptolide and prednisone acetate, with hypofunction. ACTH expression in the group of triptolide was higher than that of the control group (P < 0.05).
CONCLUSION
Morphologically and functionally, the findings suggest that long-term use of triptolide may result in atrophied cortex and hypofunction of the adrenal gland, leading to augmented production and secretion of CRH and ACTH from respective hypothalamic and pituitary.
Adrenal Cortex/physiopathology*
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Adrenocorticotropic Hormone/metabolism*
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Animals
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Corticotropin-Releasing Hormone/metabolism*
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Diterpenes/pharmacology*
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Epoxy Compounds/pharmacology*
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Hydrocortisone/blood*
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Hypothalamo-Hypophyseal System/physiopathology*
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Immunohistochemistry
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Male
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Phenanthrenes/pharmacology*
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Pituitary-Adrenal System/physiopathology*
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Prednisone/pharmacology*
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Propylene Glycol/pharmacology*
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Random Allocation
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Rats
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Rats, Sprague-Dawley
9.Effects of prednisone on renal FAK and Pyk2 expressions in rats with adriamycin- induced nephritis.
Xiaoying CHEN ; Juxia WANG ; Jing ZHENG ; Xinhong WU ; Ciyun LIU ; Xiuqin LIN
Journal of Southern Medical University 2014;34(8):1149-1153
OBJECTIVETo investigate the effects of prednisone on the expressions of FAK and Pyk2 in the kidneys of rats with adriamycin-induced nephritis.
METHODSThirty SD rats were randomized into normal control group, adriamycin-induced nephritic model group, and prednisone treatment group (n=10). Prednisone was administered at 10 mg/kg once daily in nephritic rats starting since the 7th day after adriamycin injection. Twenty-four-hour proteinuria was measured in the rats at different time points, and renal tissue histology was examined using transmission electron microscope. The expression levels of Pyk2, FAK and nephrin mRNA in the renal tissue were detected tested by RT-PCR, and the protein expressions of FAK, Pyk2, phosphorylated Pyk2 and phosphorylated FAK-Tyr397 were detected by Western blotting; immunohistochemistry was used for detecting nephrin protein expression in the kidney.
RESULTSCompared with the normal control group, the rats with adriamycin-induced nephritis showed significantly increased proteinuria (P<0.01), which was obviously lowered by prednisone treatment (P<0.01). Transmission electron microscopy revealed extensive fusion of the foot processes of the podocytes in the model group. Prednisone treatment promoted nephrin expression in the kidney (P<0.05). Compared with the control group, the model and prednisone treated groups showed significantly lowered nephrin mRNA expression (P<0.01) but increased FAK mRNA expression (P<0.01), but prednisone-treated group had a higher nephrin mRNA expression than the model group (P<0.05). The model group exhibited significantly increased expressions of FAK total and phosphorylated proteins, P-FAK/FAK, and P-Pyk2/Pyk2 (P<0.01), which were all lowered in the treatment group (P<0.01). Correlation analysis suggested that the expressions of FAK mRNA, FAK, pFAK, Pyk2 mRNA and pPyk2/Pyk2 were positively correlated with proteinuria (r=0.819, 0.750, 0.838, 0.762, 0.934, respectively, P<0.01).
CONCLUSIONSAdriamycin increases phosphorylated FAK and Pyk2 expressions to mediate kidney injury in rats. Prednisone inhibits Pyk2 and FAK activation, decreases proteinuria, and alleviates podocyte lesions to protect the glomerular filtration barrier.
Animals ; Doxorubicin ; Focal Adhesion Kinase 2 ; metabolism ; Kidney ; metabolism ; pathology ; Kidney Glomerulus ; Membrane Proteins ; metabolism ; Nephritis ; chemically induced ; drug therapy ; Podocytes ; pathology ; Prednisone ; pharmacology ; Proteinuria ; drug therapy ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley
10.Short-term Efficacy of Topical Immunosuppressive Agents on the Survival of Cultivated Allo-Conjunctival Equivalents.
Young Joo SHIN ; Mee Kum KIM ; Joo Youn OH ; Won Ryang WEE ; Jin Hak LEE ; Jung Hwa KO ; Hyun Ju LEE ; Jae Lim LEE ; Byung Moo MIN ; Young Suk SOHN
Korean Journal of Ophthalmology 2008;22(2):123-129
PURPOSE: To investigate the short-term efficacy of topical immunosuppressive agents on the survival of cultivated allo-conjunctival equivalents. METHODS: Twenty-five eyes of New Zealand white rabbits were included. Temporal conjunctivae were trephined to a diameter of 7.5 mm, and then cultured allo-conjunctival epithelial cells on amniotic membrane were transplanted onto them. Various immunosuppressants including steroid, cyclosporine, and rapamycin were applied topically four times a day for a week. Epithelial defects and graft edema were graded daily. Numbers of inflammatory cells were measured in H&E. PKH26 and cytokeratin 4 and 7 were immunostained. RESULTS: Earlier epithelialization was observed in 1% steroid-treated eyes and defects persisted significantly in 0.5% CsA applied eyes. In histology, PKH26 positive cells considered as donor cells were only found in 1% steroid or 0.01% rapamycin applied eyes. 1% steroid- or 0.01% rapamycin-applied eyes both showed positive staining for keratin-4 and -7. Inflammatory cells were less found in 1% steroid or 0.01% rapamycin treated eyes. CONCLUSIONS: Topical steroid or rapamycin can help to suppress acute inflammation and enhance the acute survival of transplanted conjunctival cells.
Administration, Topical
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Animals
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Cell Count
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*Cell Transplantation
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Cells, Cultured
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Conjunctiva/*cytology
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Cyclosporine/pharmacology
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Epithelial Cells/metabolism/*transplantation
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Female
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Fluorescent Antibody Technique, Indirect
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Graft Survival/*drug effects
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Immunosuppressive Agents/*pharmacology
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Keratin-4/metabolism
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Keratin-7/metabolism
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Male
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Organic Chemicals/metabolism
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Prednisone/pharmacology
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Rabbits
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Sirolimus/pharmacology
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Transplantation, Homologous