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1.
Transplant Proc ; 48(5): 1708-12, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27496476

RESUMO

INTRODUCTION: Alveolar echinococcosis is a parasitic disease caused by the larval stage of tapeworm Echinococcus multilocularis. It usually involves the liver, but can spread to other organs. The treatment of choice is a surgical resection supported by antiparasitic drugs. In the advanced stages of the disease a liver transplantation is the only option. AIM: This article presents the problems related to care of patients after liver transplantation for advanced alveolar echinococcosis. MATERIAL: Sixty-seven patients with alveolar echinococcosis were hospitalized in our clinic in the years 2000-2015. Liver transplantation has been a therapeutic option for 9 patients. We retrospectively analyzed data of qualification for the liver transplantation and the postoperative treatment. RESULTS: Follow-up time after liver transplantation ranged from 7 months to 155 months (average, 6.4 years). One patient, with a history of advanced disease (P4N1M0), died due to liver failure. One patient was lost to follow-up. After liver transplantation all patients were receiving albendazole treatment. Two patients did not follow the medical recommendations. In 1 patient, who decided to stop therapy after 1 year, the relapse of alveolar echinococcosis in the left lobe of the transplanted liver passing through the diaphragm to the pericardium was detected. In another case we suspected a relapse of alveolar echinococcosis in transplanted liver due to positive serological tests. CONCLUSION: The prognosis of patient after liver transplantation for alveolar echinococcosis is good. The main problem caused by immunosuppressive therapy is a recurrence of disease in the transplanted liver.


Assuntos
Equinococose Hepática/cirurgia , Transplante de Fígado , Adulto , Animais , Equinococose , Equinococose Hepática/mortalidade , Feminino , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
2.
Eur J Clin Microbiol Infect Dis ; 35(5): 847-56, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26946510

RESUMO

The aim of this study was to investigate human invasive isolates of enterococci, obtained through prospective surveillance in Poland. The consecutive enterococcal isolates were collected in 30 hospitals between May 2010 and June 2011, and studied by species identification, antimicrobial susceptibility testing and, for Enterococcus faecium by detection of markers specific for the hospital meroclone, multilocus VNTR analysis (MLVA) and multilocus sequence typing (MLST). Additionally, the genomic difference regions (GDRs) characteristic for lineage 78 were searched by PCR. Among 259 isolates, a nearly equal number of Enterococcus faecalis (n = 140; 54.1 %) and E. faecium (n = 112; 43.2 %) was found. The observed 14-day mortality rate of infected patients reached 18.1 %. All isolates were susceptible to linezolid and daptomycin. High-level aminoglycoside resistance occurred in over 50 % of isolates. Vancomycin resistance mediated by vanA or vanB was detected in 7.1 % of E. faecium; 71.4 % of isolates were multidrug resistant. E. faecium isolates ubiquitously carried molecular markers of hospital-associated meroclone (IS16, esp(Efm), intA of ICEEfm1) and multilocus sequence typing showed the domination of representatives of lineages 78 and 17/18 (52.7 % and 46.4 %, respectively). Isolates of lineage 78 were significantly enriched in all the GDRs studied. The recent spread of E. faecium from this lineage contributed to the observed increase of E. faecium in enterococcal invasive infections in hospitals in Poland.


Assuntos
Enterococcus/classificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Biofilmes , Criança , Pré-Escolar , Infecção Hospitalar , Enterococcus/efeitos dos fármacos , Enterococcus/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Tipagem de Sequências Multilocus , Avaliação de Resultados da Assistência ao Paciente , Polônia/epidemiologia , Vigilância da População , Adulto Jovem
3.
Eur J Clin Microbiol Infect Dis ; 32(9): 1193-203, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23558365

RESUMO

The purpose of this study was to investigate the clonal structure, antimicrobial resistance phenotypes and their determinants among early vancomycin-resistant Enterococcus faecium (VREm) isolates in Poland. Two hundred and eighty-one VREm isolates collected between 1997 and 2005 were studied. VREm isolates were characterised by multilocus sequence typing (MLST). The presence of antimicrobial resistance determinants, transposon-specific genes, IS16 and esp Efm was checked by polymerase chain reaction (PCR). Ciprofloxacin and ampicillin resistance determinants were investigated by sequencing. Two hundred and twenty-two (79 %) and 59 (21 %) VREm isolates were vanA- and vanB-positive, respectively. Among 135 representative isolates, MLST yielded 33 different sequence types (STs), of which 29 were characteristic of hospital-associated E. faecium; 128 (94.8 %) and 123 (91.1 %) isolates harboured the IS16 and esp Efm genes, and all 135 isolates were resistant to ciprofloxacin and ampicillin. Resistance to tetracycline (71.1 % isolates) was mostly associated with tetM (75.0 %) and the concomitant presence of the Tn916 integrase gene. High-level resistance to streptomycin (93.3 % of isolates) and high-level resistance to gentamicin (94.1 % of isolates) were due to ant(6')-Ia and aac(6')-Ie-aph(2″) genes, respectively, the latter of which is known to be located on various Tn4001-type transposons. Fifteen combinations of mutations in the quinolone-determining regions of GyrA and ParC were identified, including changes not previously reported, such as S83F and A84P in GyrA. Twenty-three variants of the penicillin-binding protein PBP5 occurred in the studied group, and novel insertions at amino acid positions 433 and 568 were identified. This analysis revealed the predominance of hospital-associated strains of E. faecium, carrying an abundant and divergent range of resistance determinants among early VREm isolates in Poland.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/genética , Resistência a Vancomicina/genética , Resistência a Ampicilina/genética , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Elementos de DNA Transponíveis/genética , Enterococcus faecium/isolamento & purificação , Gentamicinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Polônia , Estreptomicina/farmacologia , Tetraciclina/farmacologia , Vancomicina/farmacologia
4.
Transplant Proc ; 35(4): 1536-8, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12826214

RESUMO

BACKGROUND: Due to the risk of transmission of hepatitis C virus, the use of hepatitis C seropositive donors in heart transplantation is controversial. The transmission rate of hepatitis C in this patient population is estimated to range from 67% to 80%. Long-term clinical outcomes of heart transplant recipients of hepatitis C-positive donor hearts are not well described. We report the 5-year long-term outcome of seven hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts. METHODS: Retrospective analysis of clinical course, liver biochemistry, serology, and hepatitis C virology data. RESULTS: Seven hearts transplant recipients, six men and one woman were included in our study. After a mean follow-up of 63.3 +/- 20.4 months (range 28.2 to 85.9), four of seven (57.1%) patients are hepatitis C-negative, have normal liver function tests, and no clinical evidence of hepatitis. Three of seven (43%) have been diagnosed with hepatitis C by liver biopsy or the HCV-RNA reverse transcriptase polymerase chain reaction at a mean follow-up of 35.1 months (18.8 months posttransplantation). One had an accelerated course of hepatitis that was ultimately fatal, one was successfully treated with interferon, and the third died from other causes than liver injury. Overall, the 5-year survival was 71.4%. CONCLUSIONS: The 5-year survival of hepatitis C-naïve recipients of hearts from hepatitis C-positive donors is similar to heart transplant recipients with hepatitis-negative donor hearts. Nevertheless, the transmission rate is high and hepatitis C infection in this population can lead to considerable morbidity and accelerated, fatal hepatitis.


Assuntos
Transplante de Coração/fisiologia , Hepacivirus/isolamento & purificação , Hepatite C/transmissão , Doadores de Tecidos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Cadáver , Coração/virologia , Humanos , L-Lactato Desidrogenase/sangue , Reação em Cadeia da Polimerase/métodos , Complicações Pós-Operatórias/virologia , RNA Viral/isolamento & purificação , Estudos Retrospectivos
5.
Acta Crystallogr C ; 57(Pt 5): 513-4, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11353232

RESUMO

The X-ray structure analysis of [Ni(C(5)H(8)N(2))(4)(H(2)O)(2)]Cl(2) was undertaken to elucidate the geometry around the Ni(2+) ion. The molecule lies on a twofold axis which runs through the O-Ni-O atoms. The geometry around the Ni(2+) ion is best described as slightly distorted tetragonal bipyramidal.


Assuntos
Níquel/química , Compostos Organometálicos/química , Pirazóis/química , Cristalografia por Raios X , Estrutura Molecular
9.
Med Sci Monit ; 7 Suppl 1: 114-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-12211704

RESUMO

BACKGROUND: Magnetic resonance cholangiography is a relatively new method, hence it has not gained a proper status yet in the diagnostic algorithm in patients with bile duct diseases. Many authors believe that MRC is an effective method for the visualisation of bile ducts. The aim of the study is to evaluate MRC usefulness in patients with PSC. MATERIAL AND METHODS: The study material consisted of 4 patients with PSC (3 men and 1 woman) aged 23-50 years. Patients were subjected to liver MRI in transverse plane, and T1 and T2-weighted images were obtained. Additionally, magnetic resonance cholangiography was performed with Gyroscan 0.5 T unit and Magnevist contrast medium. RESULTS: The patients manifested cholestasis and hepatitis of different duration (range: 2-14 years). The biochemical analyses revealed FA ranging from 563 to 1114 IU/l, GGTP 157-1270 IU/L, AlAT 56-295 IU/L, AspAT 80-190 IU/L. Three out of four patients displayed significant increase in the level of ANCA antibodies. Histopathological investigation of the liver, conducted in 3 out of 4 patients, showed cholangitis et pericholangitis. ERCP was attempted in all the patients. In one case, irregular, overlapping and narrowed bile ducts were found, while in two cases it was impossible to fill intrahepatic ducts. ERCP was not performed due to technical obstacles encountered in one patient. All the subjects underwent MRC. In three cases, the segmental irregular dilatation of intrahepatic ducts was observed, while in one case intrahepatic ducts were poorly marked. The defect in the filling of initial segment of common bile duct was diagnosed in one patient. Another patient had a lesion adjacent to common bile duct--low signal intensity in T1 and the intensification after the administration of contrast medium indicate the presence of expansive process. CONCLUSIONS: 1. MRC is an accurate examination enabling the visualisation of all bile ducts in their natural size. 2. Simultaneous MRI of the liver allows for the diagnosis of focal lesions. 3. MRC may be used in those cases, where ERCP cannot be performed for technical reasons or when it is objected by the patient.


Assuntos
Colangiografia/métodos , Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Hepatite/diagnóstico , Hepatite/diagnóstico por imagem , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
10.
Med Sci Monit ; 7 Suppl 1: 175-80, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-12211715

RESUMO

BACKGROUND: Hepatotropic viruses HBV and HCV are capable of triggering autoimmune reactions (AIH). The aim of the study was the assessment of clinical course of AIH in patients with HBV and HCV, and the revision of treatment methods employed in these cases. MATERIAL AND METHODS: Among 120 patients with AIH and those qualified for antiviral therapy, 21 (17.5%) subjects were selected, including 16 with HCV (7 men and 9 women) and 5 with HBV (including 2 men and 3 women). AIH diagnosis was based on international criteria taking into account biochemical tests, autoantibodies and morphological picture of the liver. HBV infection was confirmed with the determination of HBV markers and HCV--with the presence of antiHCV and HCV RNA. RESULTS: The duration of infection at AIH diagnosis was difficult to assess in patients with HCV. AIH was diagnosed when patients were qualified for antiviral treatment. Three patients displayed high anti-LKM1, 8--ANA and SMA, two pts--ANA, two pts--SMA, one pt--ANA + pANCA and one--SMA + pANCA. Nine patients did not show hyperproteinaemia, and hypergammaglobulinaemia was not observed in 2 patients. Six patients suffered from other immunity disorders--thrombocytopenia, vasculitis, arthritis, visceral lupus erythematosus. The diagnosis of chronic hepatitis was confirmed by morphological examinations in 15 patients. Ten subjects received adrenocortical hormones, 3 patients were treated with adrenocortical hormones and azathioprine, 4 received interferon and 3 received no treatment. All patients with HBV proved HBeAg(-). In these patients, AIH symptoms developed 5-18 years after the diagnosis of HBV infection. Liver biopsy confirmed the diagnosis in 4 patients. SMA was observed in 2 subjects, ANA and SMA--in the remaining patients. All the subjects manifested typical biochemical changes as well as high IgG values. Extrahepatic exponents of immune process were observed in 3 patients. Three subjects were treated with Encorton (Prednisone), while 2 patients received Encorton and Azathioprine. CONCLUSIONS: Patients with HBV and HCV infections may manifest the features of AIH in the course of the disease, which requires careful attention while selecting treatment.


Assuntos
Doenças Autoimunes/virologia , Hepacivirus/metabolismo , Vírus da Hepatite B/metabolismo , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Viral/metabolismo , Fatores de Tempo
12.
Med Sci Monit ; 7 Suppl 1: 271-6, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-12211735

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) is an important factor responsible for chronic inflammatory conditions of the gastric mucosa. It has been demonstrated in numerous animal studies that some Helicobacter species may cause parenchymatous liver damage. The aim of the study was to investigate whether there is any correlation between the incidence of parenchymatous liver damage, and the incidence and degree of colonization of the gastric mucosa by H. pylori. MATERIAL AND METHODS: The study was carried out in the group of 30 patients (14 females, 16 males) whose mean age was 37 years, hospitalized because of parenchymatous liver damage without clinical symptoms of cirrhosis. All the patients had gastroscopy and urease tests performed, and mucosal biopsies were taken for immunomorphological investigations. The patients were divided into groups, group I comprising those with positive, and group II with negative urease test results. RESULTS: Positive urease tests were obtained in 26/30 patients (group I), 18/26 of whom demonstrated macroscopic changes of the gastric mucosa visible in gastroscopy. Group II with negative urease test results comprised 4/30 patients, 2/4 of whom had detectable changes in the gastric mucosa. The presence of H. pylori antigens was demonstrated by gastric mucosa immunomorphology in all 30 patients. The degree of invasion of H. pylori was visualized by immunofluorescence, which allowed to differentiate deep mucosal invasion of H. pylori (bacterial antigens present in lymph follicles and at the base of muciferous glands) observed in group I in 14/26 and in group II in 1/4 cases and superficial invasion (epithelium and mucosal surface) observed in group I in 12/26, in group II in 3/4. CONCLUSIONS: The obtained results may suggest more frequent H. pylori infections in subjects with parenchymatous liver damage than in the population without liver damage. Immunofluorescence seems to be a highly sensitive method allowing for detection of even small degrees of gastric mucosa colonization by H. pylori.


Assuntos
Mucosa Gástrica/microbiologia , Helicobacter pylori/metabolismo , Fígado/lesões , Fígado/microbiologia , Fígado/patologia , Adulto , Animais , Feminino , Humanos , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Urease/metabolismo
13.
Pol Merkur Lekarski ; 11(64): 340-3, 2001 Oct.
Artigo em Polonês | MEDLINE | ID: mdl-11770315

RESUMO

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Antivirais/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Interferon-alfa/efeitos adversos , Masculino , Polônia/epidemiologia , Ribavirina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
J Heart Lung Transplant ; 18(7): 701-6, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10452347

RESUMO

BACKGROUND: Patients with a PRA >10% are considered to be at greater risk for the development of not only acute cellular and humoral rejection but also increased mortality when compared to nonsensitized patients following transplantation. All patients with a PRA >10% at our institution are treated with plasmapheresis and intravenous immunoglobulin G immediately prior to cardiac transplantation. METHODS: Sixteen (Group 1) of 118 patients awaiting cardiac transplantation were found to be sensitized. These patients underwent plasmapheresis followed by 20 gm of intravenous immunoglobulin G (IVIG) immediately prior to cardiac transplantation. Group 1 was compared to the remaining 102 patients with a PRA <10% (Group 2). RESULTS: Despite more patients in Group 1 having a positive crossmatch, pulmonary hypertension, and requiring mechanical circulatory support, there was no statistically significant difference in length of stay or mortality at a mean follow-up of 21.6+/-15.0 months. There was no difference in the occurrence of mild, moderate or severe cellular rejection or humoral rejection in these sensitized patients when compared to Group 2. CONCLUSIONS: Pretransplant plasmapheresis followed by intravenous immunoglobulin G may be an effective therapy that obviates the need for a prospective crossmatch and allows sensitized patients to undergo cardiac transplantation. There is no increase in the post transplant length of stay, occurrence of rejection or short term mortality. Long term follow up is necessary to evaluate whether there is a difference in the development of late rejection, transplant vasculopathy and survival.


Assuntos
Anticorpos/sangue , Transplante de Coração/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese/métodos , Cuidados Pré-Operatórios/métodos , Adulto , Tipagem e Reações Cruzadas Sanguíneas , Terapia Combinada , Feminino , Rejeição de Enxerto/diagnóstico , Transplante de Coração/mortalidade , Transplante de Coração/estatística & dados numéricos , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/estatística & dados numéricos , Estudos Retrospectivos
16.
Transplant Proc ; 30(8): 4110-2, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9865316

RESUMO

The presented data show the combined sequential use of i.v. G for 14 days followed by PO G for 90 days is a much more effective prophylaxis for CMVD after heart transplantation than use of i.v. G for 14 days followed by PO A for 90 days. A need for hospitalization due to CMVD is significantly reduced by this new strategy. The follow-up in group II is shorter than in group I but is now at least 6 months in group II, without any new cases in the first 6 months after cardiac transplantation. Some currently unknown adverse effect of prolonged PO G, which may be present, is not identified in this analysis.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Coração , Administração Oral , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Esquema de Medicação , Feminino , Ganciclovir/administração & dosagem , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fatores de Tempo
17.
Acta Genet Med Gemellol (Roma) ; 47(3-4): 183-90, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-10916561

RESUMO

The objective of this study was to answer the question whether there is the relation between the uterine capacity, estimated by the total birth weight of fetuses, and the duration of twin gestation. The material for researches contains data received from the books of births and case records concerning the pregnant who gave births to twins in the Institute of Obstetrics and Gynecology of the Medical University in Lódz between 1970-1998. The final analysis concerned only gestations lasting more than 29 weeks, without any complications (excluding prematurity and the growth-discordant twins), and when gestational age was exactly known. The selected group was finally composed of 188 pairs of twins. The analyses considered relations between total birth weight of twins, the sex of newborn babies, parity, and the duration of gestation. The duration of the analyzed twin pregnancies was 35.6 weeks, including primiparous with 35.8 weeks, and multiparous--35.1 weeks. In the group of male-male twin pairs the average duration of pregnancy was 35.7 weeks, in unlike-sexed pairs--35.6 weeks, and in female-female pairs--35.5. In the group of the primiparous having male-male twin pairs the average duration of pregnancy was 35.1 weeks, unlike-sexed pairs--36.4 weeks and female female pairs--36.6 weeks, while in the group of multiparous relatively: 36.4, 35.4, 35.0 weeks. The total birth weight of the specific pairs of twins was from 2270 g to 6900 g (average 4794 g), while in 92% < 5500 g. In the primiparous group it was 4908.1 g. and in the multiparous group--4663.1 g. Analyzing the total twins' weight according to the fetal gender and parity it was found that in primiparous with male-male twins--4715.3, unlike-sexed--5271.6 and female-female--4967.5, whereas in multiparous relatively: 4961.5, 4692.6, 4414.0. The shortening of twin pregnancies was caused by the following factors: total body mass achieved by fetuses was > 5500 g, presence of male sex in twin pregnancies (only in primiparous), and also the multiparity.


Assuntos
Peso ao Nascer , Idade Gestacional , Gravidez Múltipla , Gêmeos , Útero/anatomia & histologia , Útero/fisiologia , Feminino , Humanos , Recém-Nascido , Masculino , Paridade , Gravidez , Caracteres Sexuais , Fatores de Tempo
18.
Breast Dis ; 10(3-4): 197-207, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15687575

RESUMO

We have developed a new X-ray imaging technique, diffraction enhanced imaging (DEI), which can be used to independently visualize the refraction and absorption of an object. The images are almost completely scatter-free, allowing enhanced contrast of objects that develop small angle scattering. The combination of these properties has resulted in images of mammography phantoms and tissues that have dramatically improved contrast over standard imaging techniques. This technique potentially is applicable to mammography and other fields of medical X-ray imaging and to radiology in general, as well as possible use in nondestructive testing and X-ray computed tomography. Images of various tissues and materials are presented to demonstrate the wide applicability of this technique to medical and biological imaging.

19.
Transplantation ; 58(2): 223-32, 1994 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-8042241

RESUMO

We have previously shown that administration of a combination low-dose cyclosporine (CsA) (1.0 mg/kg/day)/methotrexate (MTX) (450 micrograms/kg/wk) treatment significantly increases the survival of rat cardiac allografts, and may therefore potentially serve as an alternative immunosuppressive therapy designed to promote transplant survival while minimizing high-dose CsA side effects. In contrast to high-dose CsA, low-dose CsA/MTX treatment does not appear to alter IL-2 gene expression, since similar patterns of IL-2 gene transcripts were found in both low-dose CsA/MTX-treated and untreated control allografts on days 1 through 8 posttransplantation (post-tx). The mechanism(s) by which low dose CsA/MTX therapy increases the time of allograft survival remains to be elucidated. The aim of the present study was to determine the effects of low-dose CsA/MTX on the expression of the cytotoxic cytokines, TNF alpha, TNF beta, or lymphotoxin (LT), and the serine proteases HF and C11 (granzymes A and B, respectively) in rat cardiac allografts during rejection. RNA blot analysis showed significant suppression of TNF alpha, LT, HF, and C11 gene expression on days 1 through 8 post-tx in cardiac allografts from low-dose CsA/MTX-treated recipients compared with untreated allograft controls. TNF protein levels in cardiac allografts from low-dose CsA/MTX-treated recipients were also found to be significantly reduced on days 1 through 8 post-tx when compared with time-matched untreated allograft controls (P < or = 0.001). We conclude that low-dose CsA/MTX treatment, while effective in prolonging cardiac transplant survival, appears to act at the mRNA level to downregulate cytotoxic cytokine gene expression. Such trials aimed at evaluating low-dose combination therapy may afford new insight into mechanisms underlying improvement in immunosuppressive treatment.


Assuntos
Ciclosporina/uso terapêutico , Citocinas/metabolismo , Citotoxicidade Imunológica/genética , Rejeição de Enxerto/metabolismo , Transplante de Coração , Metotrexato/uso terapêutico , Serina Endopeptidases/metabolismo , Animais , Northern Blotting , Células Cultivadas , Ciclosporina/administração & dosagem , Sondas de DNA , Quimioterapia Combinada , Feminino , Expressão Gênica , Rejeição de Enxerto/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Miocárdio/metabolismo , Gravidez , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Homólogo
20.
Transplantation ; 56(2): 399-404, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8356596

RESUMO

The expression of the cytotoxic cytokines tumor necrosis factor alpha and TNF beta or lymphotoxin (LT) was assessed in rat cardiac transplants during rejection. Newborn rat cardiac grafts placed in adult rat ear pinnae were retrieved on days 1 through 10 posttransplantation; the average time to rejection, assessed by the absence of detectable electrocardiographic activity, was determined to be 7 days. Total cellular RNA and tissue homogenates were prepared from cardiac transplants in order that relative levels of TNF alpha and LT mRNA and TNF protein could be determined. A biphasic pattern of TNF alpha gene expression was consistently seen in cardiac allografts. TNF alpha mRNA transcripts were detected as early as day 2 post-tx, with peak levels appearing on day 3 post-tx. Although transcript levels decreased by day 4, a significant increase appeared again on day 6 post-tx, coincident with the onset of rejection. Similar to TNF alpha gene expression, LT transcripts demonstrated a biphasic pattern of induction. LT mRNA transcripts also reached peak levels on day 3 post-tx, with a second increase in transcript levels coincident with rejection. TNF protein levels in allografts displayed a biphasic pattern, similar to that shown by the cytokine mRNAs. Peak levels of TNF protein were detected on day 3 post-tx, with a second increase again coinciding with rejection. In contrast to TNF expression found in allografts, TNF alpha and LT mRNA transcripts were not detected in isografts on days 1 through 10 post-tx. TNF protein levels in cardiac isografts were consistently at or below the standard limits of detection, and on days 3 through 7 post-tx were significantly reduced (P < or = 0.001) when compared with time-matched allografts. Increased expression of the cytotoxic cytokines TNF alpha and LT, therefore, appears to be allograft-specific and is an early event during rat cardiac allograft rejection. In conclusion, induction of TNF gene expression may be an important early indicator of transplant rejection.


Assuntos
Regulação da Expressão Gênica/imunologia , Rejeição de Enxerto/genética , Transplante de Coração/fisiologia , Linfotoxina-alfa/genética , Fator de Necrose Tumoral alfa/genética , Animais , Biomarcadores/análise , Northern Blotting , Eletrocardiografia , Feminino , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto/imunologia , Linfotoxina-alfa/biossíntese , Masculino , Miocárdio/metabolismo , Valor Preditivo dos Testes , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Homólogo , Fator de Necrose Tumoral alfa/biossíntese
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