Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
Add more filters










Publication year range
1.
2.
Front Sociol ; 5: 9, 2020.
Article in English | MEDLINE | ID: mdl-33869418

ABSTRACT

The research in migrant selectivity largely overlooks the broader institutional processes that shape the extent to which migrants from different backgrounds are indeed positively selected. This is particularly true in the case of highly skilled migrants, whose selection may not be conditioned by migration but by education. This paper deals with this limitation by studying individual characteristics, which are often treated as unobserved selectivity, among a specific flow of educational migrants in Europe, namely, Chinese higher education students. To do so, we use a unique representative multi-country dataset of about 8,000 Chinese international students and their native-born counterparts in China, the UK, and Germany. Our evidence rules out positive selection of migrants on individuality traits such as ambition, creativity, or being a risk-taker or independently minded. This supports our argument that the prevalence of agentic models of individuality is embedded in tertiary education on a global level.

3.
Can J Gastroenterol Hepatol ; 2017: 8130596, 2017.
Article in English | MEDLINE | ID: mdl-28656129

ABSTRACT

AIM: The aim of this study is to evaluate the effects of the synbiotic Bifidobacterium lactis B94 plus inulin addition to the standard triple therapy on Helicobacter pylori (H. pylori) infection eradication rates. METHODS: Children aged 6-16 years who had biopsy proven H. pylori infection were randomly classified into two groups. The first group received the standard triple therapy consisting of amoxicillin + clarithromycin + omeprazole. The second group was treated with the standard triple therapy and Bifidobacterium lactis B94 (5 × 109 CFU/dose) plus inulin (900 mg) for 14 days, concurrently. Eradication was determined by 14C-urea breath test 4-6 weeks after therapy discontinuation. RESULTS: From a total of 69 H. pylori infected children (F/M = 36/33; mean ± SD = 11.2 ± 3.0 years), eradication was achieved in 20/34 participants in the standard therapy group and 27/35 participants in the synbiotic group. The eradication rates were not significantly different between the standard therapy and the synbiotic groups [intent-to-treat, 58.8% and 77.1%, resp., p = 0.16; per-protocol, 64.5% and 81.8%, resp., p = 0.19]. There was no difference between the groups in terms of symptom relief (p = 0.193). The reported side effects were ignorable. CONCLUSION: Considering the eradication rates, synbiotic addition to therapy showed no superiority over the standard triple therapy conducted alone. This trial is registered with NCT03165253.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Inulin/administration & dosage , Synbiotics/administration & dosage , Adolescent , Amoxicillin/administration & dosage , Bifidobacterium animalis , Breath Tests , Child , Clarithromycin/administration & dosage , Double-Blind Method , Drug Therapy, Combination , Female , Helicobacter Infections/microbiology , Humans , Intention to Treat Analysis , Male , Omeprazole/administration & dosage , Treatment Outcome
4.
J Korean Neurosurg Soc ; 57(3): 147-51, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25810852

ABSTRACT

OBJECTIVE: Neuroblastoma is one of common childhood tumors. Although its mortality is very high, there is no effective treatment yet. The aim of this project is to evaluate cytotoxic effects of melatonin (MLT) an endogen hormone and 13-cis retinoic acid (13-cis-RA) also named as isotretinoin an analogue of vitamin A on neuroblastoma SH-SY5Y cell line. METHODS: In this study, SH-SY5Y cell line was used. After cell culture, the cells were exposed to different doses of MLT and 13-cis-RA. 24 and 48 hours later. While the viabilities was estimated with MTT cell viability assay test, apoptotic indexes were calculated after staining with TUNEL based apoptosis kit. RESULTS: It was observed that MLT has very effective cytotoxic potential than 13-cis-RA on neuroblastoma cell line. At the same time, when MLT and 13-cis-RA were combined, this effect was potentiated. On the other hand, it was found that the effect of 13-cis-RA individually on neuroblastoma cells was very slight. CONCLUSION: We suggest that in the treatment of patient with neuroblastoma, MLT is very effective and also this effect can be augmented by combination with 13-cis-RA.

5.
World J Clin Oncol ; 3(6): 82-91, 2012 Jun 10.
Article in English | MEDLINE | ID: mdl-22724087

ABSTRACT

AIM: To study the expression of carbonic anhydrase (CA) 9 in human hepatocellular carcinoma (HCC) cells. METHODS: We studied CA9 protein, CA9 mRNA and hypoxia-inducible factor-1 alpha (HIF-1α) protein levels in Hep3B cells exposed in different parallel approaches. In one of these approaches, HCC cells were exposed to extreme in vitro hypoxia (24 h 0.1% O(2)) without or with interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) stimulation for the same hypoxic exposure time or exposed to normoxic oxygenation conditions without or with cytokine stimulation. RESULTS: The tumour cell line analysed showed a strong hypoxic CA9 mRNA expression pattern in response to prolonged severe hypoxia with cell-line specific patterns and a marked induction of CA9 protein in response to severe hypoxia. These results were paralleled by the results for HIF-1α protein under identical oxygenation conditions with a similar expression tendency to that displayed during the CA9 protein expression experimental series. Continuous stimulation with the cytokines, IL-1, IL-6, TNF-α and TGF-ß, under normoxic conditions significantly increased the carbonic anhydrase 9 expression level at both the protein and mRNA level, almost doubling the CA9 mRNA and CA9 and HIF-1α protein expression levels found under hypoxia. The findings from these experiments indicated that hypoxia is a positive regulator of CA9 expression in HCC, and the four signal transduction pathways, IL-1, IL-6, TNF-α and TGF-ß, positively influence CA9 expression under both normoxic and hypoxic conditions. CONCLUSION: These findings may potentially be considered in the design of anti- cancer therapeutic approaches involving hypoxia-induced or cytokine stimulatory effects on expression. In addition, they provide evidence of the stimulatory role of the examined cytokine families resulting in an increase in CA9 expression under different oxygenation conditions in human cancer, especially HCC, and on the role of the CA9 gene as a positive disease regulator in human cancer.

6.
Br J Sociol ; 63(1): 1-21, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22404384

ABSTRACT

As envisioned by T.H. Marshall, social citizenship was a corrective to the injustices caused by the capitalist market. Entitlements and protections guaranteed by the welfare state would prevent social and economic exclusions that civil and political rights, on their own, simply could not. Such protections consequently would ensure social cohesion and solidarity, as well as a productive economy and market. European welfare states successfully followed this formula for the most part of the post-World War II period, however the last couple of decades witnessed significant changes. For one, the very meaning of 'work' and 'worker' on which the welfare state is based has changed - flexibility, risk, and precariousness have become defining elements of working life. The welfare state itself has gone through a transformation as well, increasingly moving away from a system of 'passive benefits' to 'social investment' in human capital. These developments are coupled with an emphasis on education in 'active citizenship', which envisions participatory individuals who are adaptable in an increasingly globalized society, and ready to contribute at local, national and transnational levels. The emergent European social project draws on a re-alignment between these strands: work, social investment, and active participation. In this article, I consider the implications of this project for immigrant populations in Europe in particular and for the conceptions of citizenship and human rights in general. In contrast to the recent commentary on the neoliberal turn and the return of nation-state centered citizenship projects in Europe, I emphasize the broader trends in the post-World War II period that indicate a significant shift in the very foundations of good citizenship and social justice. The new social project transpires a citizenship model that privileges individuality and its transformative capacity as a collective good. Thus, while expanding the boundaries and forms of participation in society, this project at the same time burdens the individual, rather than the state, with the obligation of ensuring social cohesion and solidarity, disadvantaging not only non-European migrants but also the 'lesser' Europeans. The new social project brings into focus the relationship between universalistic individual rights and their effective exercise. I conclude that rather than treating human rights and citizenship as a dichotomy we should pay attention to their entangled practice in order to understand the contingent accomplishments and possible expansions of citizenship in Europe.


Subject(s)
Emigration and Immigration , Individuality , Social Change , Social Justice , Social Welfare/trends , Employment , Europe , Human Rights , Humans , Public Policy
7.
DNA Cell Biol ; 31(5): 820-5, 2012 May.
Article in English | MEDLINE | ID: mdl-22084937

ABSTRACT

In this study, our aim was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on the vitamin B12 therapy response in 95 patients with vitamin B12 deficiency and 92 healthy control subjects using vitamin B12, plasma total homocysteine (tHcy), and folate as the main measure of outcome. MTHFR C677T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism techniques. There were no differences in the distribution of MTHFR genotypes in the cases versus the controls. Mean concentrations of plasma tHcy and B12 vitamin were 18.84 µM and 142.47 pg/mL in patients with TT (10.5%) genotypes. Furthermore, mean concentrations of B12 vitamin after cobalamin therapy were 697.62, 656.64, and 488.76 pg/mL in patients with the CC, CT, and TT genotypes, respectively. The MTHFR 677 TT genotype has decreasing effect in B12 vitamin and increasing effect in tHcy. In comparison with the patients having CC and CT genotypes, patients with the TT genotype had a lower response to vitamin B12 therapy.


Subject(s)
Homocysteine/metabolism , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic/genetics , Vitamin B 12 Deficiency/genetics , Vitamin B 12 Deficiency/therapy , Adult , Case-Control Studies , Female , Folic Acid/blood , Genotype , Humans , Male , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Vitamin B 12/blood , Vitamin B 12 Deficiency/blood
8.
DNA Cell Biol ; 31(3): 323-30, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21790300

ABSTRACT

Age-related macular degeneration (AMD) is a disease with multifactorial etiology characterized by irreversible loss of central visual acuity. The discovery of susceptive single-nucleotide polymorphisms (SNPs) has progressed our understanding of AMD. Complement factor H (CFH) gene Y402H polymorphism and high-temperature requirement A-1 (HTRA1) LOC387715 gene A69S polymorphisms are the most important SNPs reported in the literature. Determination of genetic risk factors and genotype-phenotype relationship in AMD may result in rapid and cost-effective therapeutic applications for young and old population. In this study, we hypothesized a potential association between CFH gene Y402H and HTRA1 LOC387715 gene A69S polymorphism in Turkish AMD patients. In blood samples from a total of 252 individuals, 147 clinically diagnosed as AMD and the others control, polymorphic sites in CFH, Y402H (Tsp509I T/C), and HTRA1, LOC387715 A69S (FnuHI G/T), were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. There was significant difference between CFH genotypes in the AMD group, TT 21.8%, TC 48.3%, and CC 29.9%, and in the control subjects, TT 45% (p=0.003), TC 41% (p=0.0001), and CC 14% (p=0.0001). Further, the A69S polymorphism of LOC387715 was investigated and found to be significantly associated with AMD. LOC387715 genotypes in the AMD group were GG 30.6%, GT 38.1%, and TT 31.3% and in the control subjects were GG 59% (p=0.027), GT 39% (p=0.0001), and TT 2% (p=0.0001), respectively. We also found that Y402H C and A69S T allele were associated with AMD. This is the first study showing that Y402H and LOC387715 are associated with AMD in Turkish population.


Subject(s)
Macular Degeneration/genetics , Polymorphism, Single Nucleotide , Proteins/genetics , Aged , Aged, 80 and over , Alleles , Base Sequence , Complement Factor H/genetics , Female , Genetics, Population , Genotype , Humans , Male , Middle Aged , Turkey
9.
Am J Med Genet A ; 155A(7): 1745-52, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21626680

ABSTRACT

We present a 12-year-old girl with de novo karyotype 46,XX,del(12)(p11.1p12.1). Array CGH revealed in addition to a 10.466 Mb interstitial deletion on 12p11.1→12p12.1 a 0.191 Mb deletion on 2p16.3. The girl presented with mild facial dysmorphism consisting of microcephaly, hypertelorism, downslanting palpebral fissures, strabismus, broad nasal base, bulbous nose, short philtrum, micro/retrognathia, irregular tooth arrangement, phalangeal deformity in distal phalanges of hands, 5th finger camptodactyly, brachydactyly in feet, history of joint hypermobility, and scoliosis. She was considered to have mild to moderate mental retardation and ascertained for an autism spectrum disorder(ASD). Short arm of chromosome 12 interstitial deletions are rarely reported whereas point mutations and deletions of NRXN1, which is located on chromosome 2p16.3, are associated with ASDs. In this article we present and discuss the phenotypic consequences of a patient who was affected by deletions of two different chromosomal regions.


Subject(s)
Autistic Disorder/complications , Autistic Disorder/genetics , Cell Adhesion Molecules, Neuronal/genetics , Gene Deletion , Nerve Tissue Proteins/genetics , Scoliosis/complications , Scoliosis/genetics , Calcium-Binding Proteins , Child , Chromosome Banding , Chromosome Deletion , Chromosomes, Human, Pair 12/genetics , Comparative Genomic Hybridization , Female , Humans , Neural Cell Adhesion Molecules , Phenotype , Radiography , Scoliosis/diagnostic imaging , Spine/pathology
11.
Am J Med Genet A ; 149A(12): 2782-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19921639

ABSTRACT

We present the clinical and molecular findings in a Turkish child with a de novo mosaic ring derived from chromosome 4 with multiple cell-lines; the karyotype was 46,XY,r(4)[83]/45,XY, -4[6]/47,XY,r(4),+r(4)[5]/48,XY,r(4),+r(4),+dic r(4)[1]/46,XY[5]. The patient is a 20-month-old male who was the first pregnancy of nonconsanguineous parents. The baby was delivered at term with a birth weight of 1,700 g (<3rd centile) and a length of 46 cm. The baby had feeding difficulties and vomiting problems. He started walking at age 2 years and delayed language was observed. Facial appearance was normal, but the ears were large with abnormal structure. The hands showed bilateral clinodactyly of the 5th fingers. He had mild mental retardation, and epilepsy. Analysis of chromosomes showed 46,XY,r(4)(::p16.3 --> qter::)[67]/46,XY,r(4;4)(::p16.3 --> qter::p16.3 --> qter::)[2]/46,XY[3] by multicolor banding (MCB) technique. Array CGH delineated the size of the terminal deletion as 900 kb in 4p16.3. The Wolf-Hirschhorn critical region was preserved even though our patient had mild mental and motor retardation. While the mosaicism of the ring 4 could affect the phenotype, the deleted 900 kb distal deletion and clinical features of the patient may provide further insight into characteristic phenotype of the 4p- related syndromes.


Subject(s)
Cerebral Cortex/abnormalities , Chromosomes, Human, Pair 4/genetics , Epilepsy/complications , Hip Dislocation/complications , Mosaicism , Ring Chromosomes , Adult , Chromosome Banding , Comparative Genomic Hybridization , Epilepsy/genetics , Female , Hip Dislocation/genetics , Humans , Infant , Karyotyping , Male , Pregnancy
12.
Genet Test Mol Biomarkers ; 13(4): 547-51, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19604110

ABSTRACT

Cowden syndrome (CS), an autosomal dominant disorder, is associated with germline mutations of the PTEN (phosphatase, tensin homolog, deleted on chromosome TEN) gene. PTEN mutations were linked to several human neoplasms. Clinical diagnosis has been based on Consortium criteria, but detection of mutations in the PTEN gene has importance in accurate diagnosis. This article presents a female patient with classic features of the syndrome and gives the result of first PTEN mutation analysis result in a Turkish CS patient. The patient, who suffered from trichilemmomas, papillomatous lesions, lipomas, thyroid lesions, gastrointestinal hamartomas, and fibrocystic disease of the breast, is consistent with the diagnostic criteria of CS. The exons and intron/exon boundaries of the PTEN gene were analyzed by polymerase chain reaction and direct sequencing. We analyzed the clinical features and DNA in a Turkish patient with CS. We found a single-nucleotide substitution in the splicing acceptor site of intron 5 of the PTEN gene (IVS5-2A > C). It is not clear whether which types of PTEN mutations are responsible for particular phenotypes. This germline PTEN mutation, IVS5-2A --> C, has been reported once before, but the clinical features differ from our patient. Also, this is the first reported PTEN mutation from Turkey.


Subject(s)
Hamartoma Syndrome, Multiple/genetics , Mutation , PTEN Phosphohydrolase/genetics , Adult , Colon/pathology , Female , Hamartoma Syndrome, Multiple/pathology , Humans , Polymerase Chain Reaction , Sequence Analysis, DNA , Skin/pathology , Turkey
13.
Pediatr Int ; 48(3): 284-6, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16732796

ABSTRACT

BACKGROUND: Taurine (2-aminoethane sulphonic acid) is normally present in most mammalian tissues and the most abundant free amino acid in lymphocytes. It participates in various important physiological activities including modulation of the functioning of the central nervous system, cell proliferation, viability and prevention of oxidant-induced injury in many tissues. Its levels in human milk are very high which may be the most important difference from cow's milk. In contrast, an inverse association between breast-feeding and carcinogenesis in childhood or later in life has been suggested by several studies. METHODS: The study group consisted of eight healthy infants. Peripheral blood was collected and lymphocytes were cultured with either Taurine or Mitomycin C (MMC). Sister chromatid exchange in lymphocytes of the infants were calculated. RESULTS: Statistical differences were found between untreated and MMC-treated lymphocytes, untreated and MMC plus taurine-treated lymphocytes, and between MMC and MMC plus taurine-treated lymphocytes (P = 0.012). CONCLUSION: The results indicated that taurine plays a protective role in MMC-induced sister chromatid exchange in human lymphocytes. The authors suggest that the high levels of taurine found in human milk may induce protecting effects from breast-feeding against DNA damage and malignancy.


Subject(s)
Lymphocytes/drug effects , Lymphocytes/physiology , Sister Chromatid Exchange/drug effects , Taurine/pharmacology , Alkylating Agents/pharmacology , Cell Culture Techniques , Female , Humans , Infant , Infant Formula , Male , Mitomycin/pharmacology
14.
Br J Plast Surg ; 58(7): 988-96, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16040019

ABSTRACT

In this study, we aimed to investigate the efficacy of cell based dressing with living allogenic keratinocytes in diabetic foot patients. To address this issue, the cultured keratinocytes were attached to the microcarriers produced from polyethylene and silica. The microcarriers were then applied to the wounds at 3-day intervals. Forty patients with grade II and III diabetic foot ulcers were included into the study. The patients were randomised into two groups (n=20). The treatment and control groups received cell based dressing and microcarriers kept in culture medium overnight, respectively. The wound size was recorded at 3 days intervals. The wounds were also categorised by a specific scoring system considering the wound contraction, granulation tissue formation, epithelisation and discharge from the wounds. The high score indicates better condition. The mean reduction of the wound area was 92% in the treatment group and 32% in the control group at the end of the 30 days treatment (p<0.001). When considered the complete healing, the mean number of dressings was 9.2+/-3.2 in the treatment group whereas it was 16.5+/-2.3 in the control group (p<0.001). The initial mean score of the treatment and control groups were 2.5 and 2.35, respectively. At the end of the 30th day, the mean score of the treatment group was 17.15+/-2.7 and of control group was 9.05+/-3. Allogenic keratinocyte treatment delivered with microcarriers can make significant contributions to wound healing in diabetic foot patients.


Subject(s)
Biological Dressings , Diabetic Foot/therapy , Keratinocytes/transplantation , Capsules , Cell Culture Techniques/methods , Chronic Disease , Diabetic Foot/pathology , Female , Graft Survival , Granulation Tissue/pathology , Humans , Treatment Outcome , Wound Healing
15.
Biomaterials ; 26(25): 5187-97, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15792546

ABSTRACT

Cartilage engineering is a very novel approach to tissue repair through use of implants. Matrices of collagen containing calcium phosphate (CaP-Gelfix), and matrices of poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) were produced to create a cartilage via tissue engineering. The matrices were characterized by scanning electron microscopy (SEM) and electron diffraction spectroscopy (EDS). Porosity and void volume analysis were carried out to characterize the matrices. Chondrocytes were isolated from the proximal humerus of 22 week-old male, adult, local albino rabbits. For cell type characterization, Type II collagen was measured by Western Blot analysis. The foams were seeded with 1x10(6) chondrocytes and histological examinations were carried out to assess cell-matrix interaction. Macroscopic examination showed that PHBV (with or without chondrocytes) maintained its integrity for 21 days, while CaP-Gelfix was deformed and degraded within 15 days. Cell-containing and cell-free matrices were implanted into full thickness cartilage defects (4.5 mm in diameter and 4 mm in depth) at the patellar groove on the right and left knees of eight rabbits, respectively. In vivo results at 8 and 20 weeks with chondrocyte seeded PHBV matrices presented early cartilage formation resembling normal articular cartilage and revealed minimal foreign body reaction. In CaP-Gelfix matrices, fibrocartilage formation and bone invasion was noted in 20 weeks. Cells maintained their phenotype in both matrices. PHBV had better healing response than CaP-Gelfix. Both matrices were effective in cartilage regeneration. These matrices have great potential for use in the repair of joint cartilage defects.


Subject(s)
Cartilage/growth & development , Collagen/pharmacology , Guided Tissue Regeneration/methods , Polyesters/pharmacology , Tissue Engineering/methods , Absorbable Implants , Animals , Calcium Phosphates/chemistry , Cartilage/injuries , Cartilage/pathology , Cell Culture Techniques/methods , Chondrocytes/cytology , Chondrocytes/drug effects , Chondrocytes/metabolism , Collagen/chemistry , Collagen/ultrastructure , Collagen Type II/metabolism , Implants, Experimental , Knee Injuries/pathology , Knee Injuries/therapy , Male , Microscopy, Electron, Scanning , Microscopy, Energy-Filtering Transmission Electron , Polyesters/chemistry , Porosity , Rabbits
16.
Pediatr Int ; 46(4): 415-8, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15310305

ABSTRACT

BACKGROUND: Benzathine penicillin G (BPG) is a widely used antibiotic for treatment or prophylaxis of certain infectious diseases. Previous in vivo studies using sister chromatid exchange (SCE) frequency and comet assay, had showed that long-term administration of benzathine penicillin G may cause some degree of DNA damage in children with rheumatic fever. METHODS: Because DNA damage has also been reported in various connective tissue disorders, to rule out the possible effects of underlying disease on DNA integrity, 3-day-cultured lymphocytes obtained from nine healthy individuals were exposed to BPG at different concentrations (0.002, 0.02 and 0.1 micro g/mL), and sister chromatid exchange frequencies were studied. The mean SCE frequency per metaphase was calculated from 20 selected cells for each individual. RESULTS: The incidence of SCE frequency did not differ when all groups were compared. Comparing between each concentration group, exposure to BPG did not cause a dose-dependent increase in SCE frequency (Student's t-test, P > 0.05). CONCLUSION: Insignificant changes (P > 0.05) in SCE, within the 3-day exposure to BPG, may suggest that DNA damage did not occur. Short-term exposure to BPG does not have toxic effects on DNA. In contrast, this preliminary study should be supported by other genotoxicity assays, expanding the exposure time to longer periods, in order to exclude rapid DNA repair mechanisms. and a possible role of underlying disease on DNA integrity should not be ignored.


Subject(s)
DNA Damage , Lymphocytes/drug effects , Penicillin G Benzathine/pharmacology , Adolescent , Adult , Anti-Bacterial Agents/pharmacology , Dose-Response Relationship, Drug , Female , Humans , Lymphocytes/metabolism , Male , Sister Chromatid Exchange/drug effects
17.
Plast Reconstr Surg ; 111(1): 275-82; discussion 283-5, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12496589

ABSTRACT

Cyclosporine A, one of the most potent immunosuppressive drugs, mediates some of its immunosuppressive and nephrotoxic effects by enhancing transforming growth factor-beta secretion and receptor expression. In this experimental study, the effect of cyclosporine pretreatment of cultured dermal fibroblasts on xenogeneic tissue rejection after microimplantation beneath skin grafts was investigated. The effects of the site-specific immunosuppressive strategy on skin xenograft survival were tested. Because the skin is an immunological indicator of the rejection of composite tissue allografts, it was considered that this strategy could be used as a supportive therapy for composite tissue allotransplantation in the future. In the first stage of the study, fibroblast cultures obtained from skin biopsy samples from five rats were treated with different single doses of cyclosporine (100 to 3000 ng/ml), and transforming growth factor-beta levels were measured in culture supernatants after 72 hours. In the second stage, 60 Sprague-Dawley rats were divided into six groups, as follows. For group I (sham), only the standard grafting procedure was performed. For group II, after the standard grafting procedure, rats were treated with intraperitoneal injections of 30 mg/kg (n = 5) or 10 mg/kg (n = 5) cyclosporine for 10 days. For group III, cultured fibroblasts obtained from skin biopsy samples from rats were treated with 100 or 500 ng/ml cyclosporine, and the cells were collected by light trypsinization and centrifugation after 72 hours. After the standard skin grafting procedure, modified fibroblasts were implanted between the graft and the recipient bed with a Pasteur pipet. For group IV, the same procedures as for group III were performed and then rats were treated with 10 mg/kg cyclosporine, administered intraperitoneally, for 10 days. For group V, in addition to standard grafting, unmodified fibroblasts (not treated with cyclosporine) were implanted between the graft and the recipient bed. For group VI, the same procedures as for group V were performed and then rats were treated with 10 mg/kg cyclosporine, administered intraperitoneally, for 10 days. The rejection process was observed macroscopically, and statistical significance was determined with the Mann-Whitney test (p < 0.01). Graft survival times were significantly prolonged in groups III and IV, compared with groups I, II, V, and VI (p < 0.001). No difference between groups III and IV was observed. The novel finding of this investigation is that xenogeneic skin graft survival times could be prolonged with microimplantation of cyclosporine-treated cultured fibro-blasts.


Subject(s)
Fibroblasts/transplantation , Graft Survival , Skin Transplantation , Transplantation, Heterologous , Animals , Cells, Cultured , Cyclosporine/administration & dosage , DNA/biosynthesis , Fibroblasts/drug effects , Fibroblasts/metabolism , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/administration & dosage , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta/biosynthesis , Transforming Growth Factor beta1
SELECTION OF CITATIONS
SEARCH DETAIL
...