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1.
Med Intensiva ; 41(7): 401-410, 2017 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28522141

RESUMO

INTRODUCTION: The way to assess tissue perfusion during the resuscitation of patients with severe sepsis and septic shock is a current subject of research and debate. Venous oxygen saturation and lactate concentration have been the most frequently used criteria, though they involve known limitations. The venous-to-arterial difference of carbon dioxide (pCO2 delta) is a parameter than can be used to indicate tissue perfusion, and its determination therefore may be useful in these patients. METHODS: A qualitative systematic review of the literature was made, comprising studies that assessed pCO2 delta in adult patients with severe sepsis or septic shock, and published between January 1966 and November 2016 in the Medline-PubMed, Embase-Elsevier, Cochrane Library, and LILACS databases. There was no language restriction. The PRISMA statement was followed, and methodological quality was evaluated. RESULTS: Twelve articles were included, all of an observational nature, and including 10 prospective studies (9 published since 2010). Five documented greater mortality among patients with high pCO2 delta values, in 3 cases even when achieving venous oxygen saturation targets. In 4 studies, a high pCO2 delta was related to lower venous oxygen saturation and higher lactate levels, and another 3 documented lesser percentage lactate reductions. CONCLUSION: The parameter pCO2 delta has been more frequently assessed in the management of patients with severe sepsis during the last few years. The studies demonstrate its correlation to mortality and other clinical outcomes, defining pCO2 delta as a useful tool in the management of these patients.


Assuntos
Dióxido de Carbono/sangue , Sepse/sangue , Adulto , Artérias , Débito Cardíaco , Humanos , Hipóxia/sangue , Hipóxia/diagnóstico , Hipóxia/etiologia , Lactatos/sangue , Estudos Observacionais como Assunto , Pressão Parcial , Estudos Prospectivos , Sepse/complicações , Sepse/terapia , Choque Séptico/sangue , Choque Séptico/complicações , Choque Séptico/terapia , Veias
2.
RSC Adv ; 12(28): 17661-17674, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35765323

RESUMO

The effect of two different anionic membranes on manganese deposition was studied in a two-compartment electrochemical reactor with a titanium cathode and a dimensionally stable RuO2|Ti anode. Chronopotentiometry, ICP-OES, SEM, XRD and elemental mapping were used to understand the changes in concentration and characteristics of the metallic deposition at different current densities with the anionic membranes AMI 7001s and Neosepta AMX. The results demonstrate that AMI reduces more manganese than AMX below -100 A m-2, generating more metallic deposition but also more low-solubility manganous by-products, whereas both membranes exhibited similar behaviours above -100 A m-2 reaching the maximum current efficiency (63%) at -200 A m-2. It was also observed that the membranes have a significant effect on sulphate consumption since they are anions.

3.
RSC Adv ; 11(41): 25542-25550, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35478895

RESUMO

Electrochemical reduction of ionic species during manganese deposition from sulphated aqueous solutions has been studied in an electrochemical reactor with two anionic exchange membranes. Thermodynamic analysis, voltammetries, and chronopotentiometries were used to determine the reaction mechanism of the reductions developed, with the results demonstrating that the effect of the elemental selenium on the hydrogen evolution leads to the formation of elemental sulphur by reducing the sulphate ions with both membranes. It was also evident that in the range of -25 to -50 A m-2 the electrodeposition of metallic manganese begins, with minimal interference from parasitic reactions.

4.
J Exp Med ; 187(11): 1735-43, 1998 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9607915

RESUMO

To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vlambda1 light chain genes from naive and memory B cells in DNA repair-deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand-break repair, and AAG-mediated base excision repair.


Assuntos
Linfócitos B/imunologia , Reparo do DNA/fisiologia , Rearranjo Gênico do Linfócito B , Genes de Imunoglobulinas , Memória Imunológica/imunologia , Mutação , Animais , Região Variável de Imunoglobulina/genética , Cadeias lambda de Imunoglobulina/genética , Camundongos , Camundongos Mutantes , Reação em Cadeia da Polimerase
5.
Cir Pediatr ; 23(4): 245-9, 2010 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-21520559

RESUMO

AIM: To analyze the benefits of Split (for adult and for child) in liver transplantation. PATIENT/METHODS: 1) Analysis of the waiting list mortality estimated on 228 inclusions for transplant since January 2004 to December 2008.2) Impact of the variant techniques (living-related donor and split) on the waiting list mortality in our patients. 3) Analysis of the outcome of 33 split livers which allowed to perform 66 transplants (1994-2008). RESULTS: Estimated as number of patients by 1,000 candidates by year of exposure, the waiting list mortality was 110 in children older than 5 year old, 180 in children from 2 to 5 year-old, 90 in children between 1 and 2 year-old and 510 in younger than 1 year (p<0.05 for the last group). 36/66 split grafts were implanted by our group. Five grafts were lost, 3 due to retransplantation and 2 due to death. Overall patient/graft survival alter 10 years of follow-up was 94.5% and 85.1%, respectively. The rest of the grafts (n=30), were used in other hospitals, and 4 were lost in the early postoperative period. Since the beginning of the study, 85.4% of children between 1 and 2 years, received a living-donor or a split graft, as only 59.9% in the younger than 1 year-old group. CONCLUSION: Our results absolutely justify the ethics of split liver transplantation for an adult and a child. Despite other factors, the benefits of the variant techniques in the 1-2 year-old group are obvious. Up to 60% optimization with these techniques in children younger than 1 year would not be yet enough in order to decrease the mortality waiting list down to that of the rest of the groups.


Assuntos
Hepatectomia/métodos , Transplante de Fígado , Obtenção de Tecidos e Órgãos/métodos , Adulto , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos
6.
Cir Pediatr ; 23(3): 177-83, 2010 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-23155666

RESUMO

OBJECTIVE: To analyze the evolution of Small Bowel Transplantation program since the beginning of the program. MATERIAL AND METHODS: [corrected] All children who underwent intestinal transplantation between 1997 and 2009 were retrospectively reviewed: epidemiological data, status before transplant, surgical technique, immunosupression, results, survival and long.term quality of life were analysed. RESULTS: Fifty-two intestinal transplants were performed in 46 children (20 isolated bowel, 20 combined liver and intestine, and 12 multivisceral); median age was 32m (range 7m-19a); weight 12,3 kg (range 3,9-60); 31 had short gut syndrome, 8 dismotility, 5 intractable diarrhea, and two were miscellaneous. Intestinal adaptation was initially attempted in 26 patients, without success, 20 were directly listed for transplant. The modality of transplant was modified in 17 while listed. Baseline immunosupression consisted of tacrolimus and steroids, although 5 required conversion to Sirolimus later. Six died during the first month, due to sepsis/multiorganic failure (poor status at transplant); 13 died during the long-term follow-up. Acute rejection was seen in 20, chronic rejection in 3, PTLD in 8 (6 died) and GVHD in 5 patients (3 died). Overall survival after 5 years of follow-up is 65,2 % (51,7% for the graft). From 2006 to 2008, overall patient/graft survival at 6 m, 1 and 3 years after transplant is 88,7/84,1, 81,2/81,2 and 81,2/71,1%, respectively. After a median follw-up of 39 +/- 29 months, 27 patients are alive (59%), off TPN, (70% had their ostomy taken down), go to school, are scarcely hospitalized and enjoy a good quality of life. CONCLUSIONS: Intestinal transplantation has consolided itself as a good choice for irreversible intestinal failure, being feasible to achieve a normal life. Although overall survival diminishes over time, the center experience has improved the results. These patients need a very close follow-up, once transplant is over, in order to get an early diagnose of immunological complications.


Assuntos
Enteropatias/cirurgia , Intestino Delgado/transplante , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Adulto Jovem
7.
Vet Parasitol ; 281: 109120, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32361525

RESUMO

The histological findings associated to Besnoitia besnoiti infection were exhaustively studied in target tissues from experimentally and chronically infected calves. Calves were inoculated with 106 bradyzoites via intravenous, subcutaneous and intradermal route. Visible pathognomonic sclera cysts were observed in all infected animals. Tissue cysts were more abundant and lesions were more frequent in calves inoculated via intradermal. The most parasitized tissues were skin, including scrotum (40.81% of positive samples), nostril and nasal turbinate. Tissue cysts were already fully developed as the average tissue cyst diameter was 181.20 µm. Microscopic lesions were mainly detected in skin samples, followed by reproductive and upper respiratory tracts. Mild lesions compatible with both acute (thrombus, oedema and inflammation) and chronic besnoitiosis (skin lesions, hyperkeratosis and dilated sweat glands) coexisted. Vascular damage and inflammation were more frequently observed in skin (including scrotum) followed by testicular parenchyma, epididymis and pampiniform plexus. Histological findings evidenced a subclinical chronic besnoitiosis.


Assuntos
Doenças dos Bovinos/patologia , Coccidiose/veterinária , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Doença Crônica , Coccidiose/patologia , Masculino
8.
J Cell Biol ; 154(1): 49-60, 2001 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-11448989

RESUMO

Poly(ADP-ribose) polymerase (PARP)-1, a detector of single-strand breaks, plays a key role in the cellular response to DNA damage. PARP-1-deficient mice are hypersensitive to genotoxic agents and display genomic instability due to a DNA repair defect in the base excision repair pathway. A previous report suggested that PARP-1-deficient mice also had a severe telomeric dysfunction consisting of telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P. Hande, W.-M. Tong, P.M. Lansdorp, Z.-Q. Wang, and S.P. Jackson. 1999. NAT: Genet. 23:76-80). In contrast to that, and using a panoply of techniques, including quantitative telomeric (Q)-FISH, we did not find significant differences in telomere length between wild-type and PARP-1(-/)- littermate mice or PARP-1(-/)- primary cells. Similarly, there were no differences in the length of the G-strand overhang. Q-FISH and spectral karyotyping analyses of primary PARP-1(-/)- cells showed a frequency of 2 end-to-end fusions per 100 metaphases, much lower than that described previously (d'Adda di Fagagna et al., 1999). This low frequency of end-to-end fusions in PARP-1(-/)- primary cells is accordant with the absence of severe proliferative defects in PARP-1(-/)- mice. The results presented here indicate that PARP-1 does not play a major role in regulating telomere length or in telomeric end capping, and the chromosomal instability of PARP-1(-/)- primary cells can be explained by the repair defect associated to PARP-1 deficiency. Finally, no interaction between PARP-1 and the telomerase reverse transcriptase subunit, Tert, was found using the two-hybrid assay.


Assuntos
Cromossomos/química , Cromossomos/ultraestrutura , Poli(ADP-Ribose) Polimerases/genética , RNA , Telômero/química , Telômero/ultraestrutura , Animais , Células da Medula Óssea/metabolismo , Divisão Celular , Células Cultivadas , DNA Complementar/metabolismo , Proteínas de Ligação a DNA , Genótipo , Heterozigoto , Hibridização in Situ Fluorescente , Cariotipagem , Camundongos , Camundongos Transgênicos , Poli(ADP-Ribose) Polimerases/fisiologia , Baço/citologia , Telomerase/metabolismo , Técnicas do Sistema de Duplo-Híbrido
9.
Cir Pediatr ; 22(3): 119-21, 2009 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-19957856

RESUMO

AIM: Even though Spain has the highest donation rate in the world, our needs cannot be satisfied, specially in younger children. Living-related donor transplant is an alternative in those cases. PATIENTS AND METHOD: We performed a retrospective study of 57 living-related donor transplants performed in our hospital between June 1993 and December 2007. Median age and weight were 1.2 years old (0.5-14.8) and 8.5 kg (5-62). Indications for transplant were as follow: biliary atresia in 42 cases (73.7%), hepatic tumor in 8 (14%) and others in 7 patients. Type of graft was: monosegment (n=1), left lateral segment (n=45), extended left lateral segment (n=5), left liver (n=4), right liver (n=2). We studied the following factors: graft and patient survival (Kaplan Meier), perioperative conditions, complications, causes of graft lost, donor complications and technique difficulties. RESULTS: Patient survival at 3 months, 1 year, 5 years and 10 years was 98.2%, 98.2%, 95% and 95% respectively. Three grafts werelost due to arterial thrombosis, two due to rejection, one due to portal thrombosis and three due to other causes. Complications were as follow: biliary fistula in the cut surface (6), biliary anastomosis complications (6), cut surface abcess (1), portal stenosis (2), suprahepatic stenosis (1) and intestinal perforation (2). Most common complication in donors was biliary leak (4). Among the technique difficulties, 8 patients needed major reconstruction of suprahepatic vein; 4 needed complex portal reconstruction, 6 patients had double biliary tract and 4 patients needed multiple arterial anastomosis. Wall closure was delayed (Goretex) in 35% of cases (20). CONCLUSIONS: Despite technical complications, results after living-related donor transplantation are excellent. It is particularly favourable for children with low weight, since Spanish policy for organ allocation does not make easy to find an adecuate donor in short periods of time. Without living-related donor transplantations, mortality pretransplant would be much higher.


Assuntos
Transplante de Fígado , Doadores Vivos , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos , Resultado do Tratamento
10.
Cir Pediatr ; 22(3): 122-4, 2009 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-19957857

RESUMO

AIM: Liver pediatric transplantation finds in the lack of donors its main limitation. An alternative in those cases is split liver grafts from bigger donors. PATIENTS AND METHOD: We performed a retrospective study of 56 hepatic split transplants performed between 1994 and 2007. Twenty-nine children were transplanted with a median age and weight of 1.8 years old (0.3-9) and 9.7 kg (6.2-23). In 16 cases (53.3%) liver transplant was performed in emergency situation. In one patient we performed a combined transplant (liver-kidney) and in another patient it was a second transplant due to primary graft failure after receiving an hepatointestinal allograft. Type of grafts used were: lateral left segment (n=26), extended lateral left segment (n=1) and extended right liver (n=3). Median donor age and weight were 20 years old (8-44) and 60 kg (24-80). We studied patient and graft survival (Kaplan Meier), perioperative factors, complications and net rate of early complications in adults recipients. RESULTS: Patient survival was 96.7% after 6 months, 1 year, 5 years and 10 years. Id for grafs 86.7%. Two grafts were lost due to arterial thrombosis, one due to primary non function and another due to recipient death secondary to a sepsis. Five children had major biliary complications and 2 of them developed multiple intrahepatic stenoses, one of them being on waiting list for retransplant. Early graft lost (retransplant or death before leaving the hospital) occurred in 4 out of the 25 grafts transplanted in other centers (25 adults, 1 kid); all of them occurred in the initial period (1994-2001). CONCLUSIONS: Even though it is clearly documented that benefit of transplant (measured in years of life won) is very good after split transplantation, nowadays criteria for organ allocation in Spain do not allow a more extensive diffusion of this technique and it is confined to urgent transplant. Even in those cases, results after split transplantation are excellent. Without this possibility our pretransplant mortality would be much higher.


Assuntos
Hepatectomia/métodos , Transplante de Fígado/métodos , Criança , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos
11.
Trends Biochem Sci ; 19(4): 172-6, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8016868

RESUMO

Poly(ADP-ribose) polymerase (PARP) participates in the intricate network of systems developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents. Cloning of the PARP gene has allowed the development of genetic and molecular approaches to elucidate the structure and function of this abundant and highly conserved enzyme.


Assuntos
Poli(ADP-Ribose) Polimerases , Animais , Humanos , Poli Adenosina Difosfato Ribose/biossíntese , Poli(ADP-Ribose) Polimerases/química , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Sequências Repetitivas de Ácido Nucleico
12.
Vet Parasitol ; 267: 21-25, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30878080

RESUMO

In a previous attempt, an experimental model of bovine besnoitiosis was established in calves that were intravenously inoculated with different doses of Besnoitia besnoiti tachyzoites. Despite the fact that all infected calves developed the acute stage of disease, only microscopic findings characteristic of chronic besnoitiosis were reported. In the present study, calves were inoculated by subcutaneous and intradermal routes with B. besnoiti tachyzoites with the aim of developing clinical signs and macroscopic lesions characteristic of chronic besnoitiosis. Nine 3-month-old male calves were randomly distributed into three groups of three animals each. Next, 106 tachyzoites were inoculated by either the subcutaneous (G1) or intradermal route (G2). The negative control group (G3) was inoculated with PBS. Daily clinical monitoring and regular blood collection were performed. At 70 days post-infection (pi), animals were euthanized, and tissues were collected to investigate lesions and parasites. Infected animals developed mild-moderate acute besnoitiosis characterized by lymphadenopathy from four days to 47 days pi, and sporadic fever peaks were only observed in one calf from G2. However, other clinical signs and macroscopic lesions characteristic of chronic besnoitiosis were not detected. Only nine tissue samples were B. besnoiti-DNA-positive, eight of which belonged to reproductive and respiratory tracts tissues from G1. Finally, the kinetics of the immune responses were similar in both infected groups. However, delayed and lower cellular and humoral immune responses were observed in G1 followed by G2 and were compared with intravenously inoculated calves. The differences observed among the three inoculation routes could be due to different effector mechanisms of the host early innate immune response against B. besnoiti. Accordingly, the inoculation route of B. besnoiti tachyzoites does not significantly influence the clinical outcome of the infection in calves. Thus, a further refinement of this experimental model of bovine besnoitiosis is needed to reproduce macroscopic lesions characteristic of chronic stage disease.


Assuntos
Doenças dos Bovinos/prevenção & controle , Coccidiose/veterinária , Modelos Animais de Doenças , Animais , Anticorpos Antiprotozoários/sangue , Bovinos , Doenças dos Bovinos/parasitologia , Imunidade Humoral , Imunoglobulina G/sangue , Injeções Intradérmicas , Linfadenopatia/etiologia , Linfadenopatia/parasitologia , Masculino , Sarcocystidae , Absorção Subcutânea
13.
Cell Death Differ ; 14(6): 1149-61, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17347666

RESUMO

Several different autosomal recessive genetic disorders characterized by ataxia with oculomotor apraxia (AOA) have been identified with the unifying feature of defective DNA damage recognition and/or repair. We describe here the characterization of a novel form of AOA showing increased sensitivity to agents that cause single-strand breaks (SSBs) in DNA but having no gross defect in the repair of these breaks. Evidence for the presence of residual SSBs in DNA was provided by dramatically increased levels of poly (ADP-ribose)polymerase (PARP-1) auto-poly (ADP-ribosyl)ation, the detection of increased levels of reactive oxygen/nitrogen species (ROS/RNS) and oxidative damage to DNA in the patient cells. There was also evidence for oxidative damage to proteins and lipids. Although these cells were hypersensitive to DNA damaging agents, the mode of death was not by apoptosis. These cells were also resistant to TRAIL-induced death. Consistent with these observations, failure to observe a decrease in mitochondrial membrane potential, reduced cytochrome c release and defective apoptosis-inducing factor translocation to the nucleus was observed. Apoptosis resistance and PARP-1 hyperactivation were overcome by incubating the patient's cells with antioxidants. These results provide evidence for a novel form of AOA characterized by sensitivity to DNA damaging agents, oxidative stress, PARP-1 hyperactivation but resistance to apoptosis.


Assuntos
Apoptose/fisiologia , Quebras de DNA de Cadeia Simples , Estresse Oxidativo , Poli(ADP-Ribose) Polimerases/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Apraxias/metabolismo , Apraxias/patologia , Apraxias/fisiopatologia , Ataxia/metabolismo , Ataxia/patologia , Ataxia/fisiopatologia , Western Blotting , Camptotecina/farmacologia , Células Cultivadas , Dano ao DNA , Reparo do DNA , Etoposídeo/farmacologia , Feminino , Citometria de Fluxo , Humanos , Peróxido de Hidrogênio/farmacologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Potencial da Membrana Mitocondrial/efeitos da radiação , Metilnitronitrosoguanidina/farmacologia , Mitomicina/farmacologia , Poli(ADP-Ribose) Polimerase-1 , Radiação Ionizante , Espécies Reativas de Nitrogênio/metabolismo
14.
Eur J Pediatr Surg ; 18(6): 372-4, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19039737

RESUMO

INTRODUCTION: Several variant techniques have been developed as alternatives to whole liver transplantation to improve size matching, timing, or simply to increase the pool of donors. The aim of this study was to assess the requirements of these techniques and their outcomes in a pediatric transplant program. PATIENTS AND METHOD: A retrospective analysis of children on the waiting list in the last 4 years was carried out. Data of patients who died while on the waiting list (WL) were recorded. Transplanted patients were divided according to the type of graft: whole liver, split, living donor and reduced liver. The analyzed outcome variables were: age, weight, UNOS status, cause of liver failure, complications and graft and patient survival. Comparisons between types of graft were performed by using Kaplan-Meier, log-rank, chi (2) and Kruskal-Wallis tests. RESULTS: During the period studied, 116 children were listed for liver transplantation. Of these 116 children, nine (7.7 %) died after a mean period of 40.5 (5-175) days waiting for a suitable graft. Their median age at inclusion was 214 (35-1607) days, and median weight was 7.2 (12.3-3.6) kg. The cause of liver failure in this group was: 1 hemochromatosis, 1 hepatoblastoma, 2 biliary atresia, 2 acute liver failure, 2 primary non-function (PNF) and 1 chronic rejection. Liver transplantation was performed in 103 children: 25 (24 %) whole livers, 17 (16.5 %) split, 29 (28 %) living donor, 32 (31 %) reduced and 4 remain on the waiting list. Recipient age and weight were significantly lower in those receiving split and living donor than in those who given whole livers. Patient and graft survival were similar in all groups although there was a trend to lower graft survival in patients receiving whole livers. More than 50 % of patients with UNOS status I received a split graft and 5/6 children with hepatoblastoma underwent living donor transplantation. There were no differences in the rate of acute vascular complications, but long-term biliary complications were more frequent in split and living donor grafts. CONCLUSIONS: As long as the goal of zero mortality for children on the waiting list is not achieved, variant techniques will be necessary in pediatric liver transplantation programs. Split and living donor were employed mostly to treat younger children and particularly those with a higher UNOS status. Children with tumors were treated mainly with living donor grafts. Variant techniques, which are absolutely necessary in a pediatric program, need to be improved in order to avoid long-term biliary complications.


Assuntos
Transplante de Fígado/métodos , Adolescente , Criança , Pré-Escolar , Sobrevivência de Enxerto , Humanos , Lactente , Doadores Vivos , Tamanho do Órgão , Estudos Retrospectivos , Espanha , Análise de Sobrevida , Resultado do Tratamento , Listas de Espera
15.
Mol Cell Biol ; 18(6): 3563-71, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9584196

RESUMO

Poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) is a zinc-finger DNA-binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these breaks, the immediate poly(ADP-ribosyl)ation of nuclear proteins involved in chromatin architecture and DNA metabolism converts DNA damage into intracellular signals that can activate DNA repair programs or cell death options. To have greater insight into the physiological function of this enzyme, we have used the two-hybrid system to find genes encoding proteins putatively interacting with PARP. We have identified a physical association between PARP and the base excision repair (BER) protein XRCC1 (X-ray repair cross-complementing 1) in the Saccharomyces cerevisiae system, which was further confirmed to exist in mammalian cells. XRCC1 interacts with PARP by its central region (amino acids 301 to 402), which contains a BRCT (BRCA1 C terminus) module, a widespread motif in DNA repair and DNA damage-responsive cell cycle checkpoint proteins. Overexpression of XRCC1 in Cos-7 or HeLa cells dramatically decreases PARP activity in vivo, reinforcing the potential protective function of PARP at DNA breaks. Given that XRCC1 is also associated with DNA ligase III via a second BRCT module and with DNA polymerase beta, our results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the detection of DNA interruptions and possibly in the recruitment of XRCC1 and its partners for efficient processing of these breaks in a coordinated manner. The modular organizations of these interactors, associated with small conserved domains, may contribute to increasing the efficiency of the overall pathway.


Assuntos
Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Adenosina Difosfato Ribose/metabolismo , Animais , Células COS , DNA Ligase Dependente de ATP , DNA Ligases/metabolismo , DNA Polimerase beta/metabolismo , Escherichia coli , Células HeLa , Humanos , Proteínas de Ligação a Poli-ADP-Ribose , Ligação Proteica , Saccharomyces cerevisiae , Proteína 1 Complementadora Cruzada de Reparo de Raio-X , Proteínas de Xenopus , Dedos de Zinco
16.
Mol Cell Biol ; 21(5): 1828-32, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11238919

RESUMO

PARP-1 and ATM are both involved in the response to DNA strand breaks, resulting in induction of a signaling network responsible for DNA surveillance, cellular recovery, and cell survival. ATM interacts with double-strand break repair pathways and induces signals resulting in the control of the cell cycle-coupled checkpoints. PARP-1 acts as a DNA break sensor in the base excision repair pathway of DNA. Mice with mutations inactivating either protein show radiosensitivity and high radiation-induced chromosomal aberration frequencies. Embryos carrying double mutations of both PARP-1 and Atm genes were generated. These mutant embryos show apoptosis in the embryo but not in extraembryonic tissues and die at embryonic day 8.0, although extraembryonic tissues appear normal for up to 10.5 days of gestation. These results reveal a functional synergy between PARP-1 and ATM during a period of embryogenesis when cell cycle checkpoints are not active and the embryo is particularly sensitive to DNA damage. These results suggest that ATM and PARP-1 have synergistic phenotypes due to the effects of these proteins on signaling DNA damage and/or on distinct pathways of DNA repair.


Assuntos
Mutação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas/genética , Proteínas/fisiologia , Animais , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia , Ciclo Celular , Proteínas de Ciclo Celular , Morte Celular , Divisão Celular , Sobrevivência Celular , Aberrações Cromossômicas , Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA , Embrião de Mamíferos/metabolismo , Genótipo , Heterozigoto , Camundongos , Microscopia Eletrônica , Modelos Biológicos , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases , Reação em Cadeia da Polimerase , Tolerância a Radiação , Transdução de Sinais , Fatores de Tempo , Proteínas Supressoras de Tumor
17.
Eur J Pediatr Surg ; 17(6): 387-92, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18072021

RESUMO

AIM: Aim of the study was to review our experience in the management of liver tumors in children over the last 15 years. PATIENTS AND METHODS: A cohort of 78 children with liver tumors managed in our institution between 1991 and 2006 was retrospectively reviewed. There were 45 males and 33 females with a mean age of 32 +/- 41 months at diagnosis. Most tumors were malignant (n = 57); the most frequently occurring tumor was hepatoblastoma (n = 47), followed by hepatocarcinoma (n = 5), sarcoma (n = 4), and lymphoma (n = 1). Vascular tumors (n = 12) predominated among the benign tumors followed by mesenchymal hamartoma (n = 4), focal nodular hyperplasia (n = 3), adenoma (n = 1), and inflammatory pseudotumor (n = 1). We reviewed the epidemiologic features, clinical presentation, diagnosis, treatment and outcomes. We employed MRI and angio-CT for SIOPEL PRETEXT staging and selected the management accordingly for malignant tumors. We analyzed the long-term survival using Kaplan-Meier curves. RESULTS: Benign tumors had an excellent outcome with both medical or surgical management. Of the malignant tumors 4 were PRETEXT I and were treated by left lateral segmentectomy with 100 % survival; 20 were PRETEXT II (12 left and 8 right lobe) and were treated by lobectomy of the corresponding side, except for 1 case which required OLT (90 % survival); 9 children had PRETEXT III tumors requiring trisegmentectomy or extended lobectomies with OLT in 1 case (77.7 % survival). Fourteen children had PRETEXT IV tumors: 10 received OLT and 9 of them are still alive (64.2 % survival). Overall survival was 80.8 %, and actuarial survival at 6 years was 82.2 %. Other malignant tumors had variable results. CONCLUSIONS: Outcomes have improved much in the last years. Surgical removal is necessary in most cases. Transplantation is a very useful adjunct. Treatment of these tumors should be concentrated in centers with expertise.


Assuntos
Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
J Sports Med Phys Fitness ; 47(3): 366-74, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17641607

RESUMO

AIM: The aim of this study is the validation in the Spanish context of the Behavioural Regulation in Exercise Questionnaire-2 (BREQ-2) scale, developed by Markland et al., from the point of view of the self-determination theory and to compare the effect of gender, age and exercise duration and mode. METHODS: For the validation of the instrument, two studies were carried out (n=250 and n=311) with a total sample formed of 561 adults in the metropolitan area of the city of Murcia, Spain, who do non-competitive sport and physical activities. They were given the adaptation of the questionnaire BREQ-2 by Markland et al. to fill in. RESULTS: After an exploratory factor analysis and a confirmatory factor analysis, an adaptation of the scale was obtained with 18 items and 5 factors with acceptable reliability coefficients and a total variance explained of 68.8%. The two highest assessed forms of behavioral regulation were intrinsic and identified, with the women showing more intrinsic regulation. Those that exercised for less time were the ones that showed higher levels of amotivation and the older people showed a greater tendency to identified regulation. CONCLUSION: The BREQ-2 scale has all the required conditions, as far as reliability and validity criteria are concerned, to be used in the Spanish context in different areas of physical activity.


Assuntos
Comportamentos Relacionados com a Saúde , Motivação , Aptidão Física , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Atividade Motora , Projetos Piloto , Psicometria , Espanha , Inquéritos e Questionários
19.
Cir Pediatr ; 20(3): 169-74, 2007 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-18018746

RESUMO

BACKGROUND: Esophagocoloplasty is one of the most used procedures for esophageal replacement in children. Considering high life expectancy in these patients, long-term results must be considered when evaluating this technique. The aim of our study is to evaluate quality of life of adult patients who underwent surgery at pediatric age. PATIENTS AND METHODS: We report a retrospective study of 99 patients who underwent esophageal replacement in our institution between 1966 and 2006. Eight of them have died and 63 out of the remaining 91 are over 18 years now and represent our study serie. Long-term results and actual situation of those patients, considering psychological, physic and social aspects, were evaluated through clinical review and telephonic interview. Karnofsky index was applied to mesure functional ability from 0-100% (bad, medium, good-excellent) according to the answers the patients gave to our questions. We also recorded their health personal experience and subjective evaluation of their quality of life. RESULTS: Sixty-three patients were reviewed (43 males and 20 females) with a mean age of 4.3 +/- 3.4 D.S. Mean follow-up time was 29.6 +/-7.7 years. Indications for esophageal replacement were as follows: caustication (n = 32), type III esophageal atresia (n = 15), type I AE (n = 13) and others (n = 3). In 48 patients the graft was placed in retroestenal position and in 15 cases retromediastic location was used. Postoperative period was uneventful in 44% of the patients, being the most frequent early complications in the remaining, cervical leakage and stenosis. Long-term, 56,8% did not have any sequelae, 28.5% required further surgery and the remaining 43.13% presented the following complications: symptomatic graft reflux (22), scoliosis and thoracic asymmetry (12), colonic redundancy or cervical diverticulum (7), food impaction (6) and failure to thrive (5). Only one 38 year old patient does not have intestinal tract continuity nowadays. Thirty-one patients have a Karnofsky index > or = 80-100%, being considered healthy and able to have a normal activity. Eighteen patients are included between 40-80%, being the most frequent limitation the need of medication to avoid reflux, backache and occasional episodes of food impact. Only 2 patients have Karnofsky index inferior to 40%. None of them are under 20%. CONCLUSIONS: Esophagocoloplasty allows restoration of intestinal tract continuity in almost all cases and the mortality of this procedure has decreased over time. Even though some risks are still remarkable, it offers long-term good results with little repercussion on functional ability in adult age. Most of the patients consider themselves healthy and enjoy an acceptable quality of life.


Assuntos
Colo/transplante , Doenças do Esôfago/cirurgia , Qualidade de Vida , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo
20.
Cir Pediatr ; 20(1): 39-43, 2007 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-17489492

RESUMO

BACKGROUND: Postoperative complications of esophageal replacement are potentially severe, and they can even make impossible the digestive continuity. However, several surgical options have been used for such situations. The aim of the study is to assess the early and late results in patients who have been managed or referred to our department for this problem. PATIENTS AND METHODS: We reviewed 8 patients operated between 1975 and 2005, four of them were referred from other hospitals. The ranging in age was from 4 months and 23 years at the moment of the first colonic replacement, and who required a second plasty because of intra or postoperative complications. The esophagocoloplasty was retrosternal in 6 cases and transhiatal in 2, with a left colon graft in 6, ileocolonic in I and right colon in the last one. The initial diagnosis was traqueoesophageal fistula in 6 (type III in 3, type I in 2 and IV in 1), caustic injury in 1 and herpetic esophagitis in 1. Complications requiring reoperation were stricture of the cervical esophagococolic anastomosis because of postoperative dehiscence (n=4), perioperative deficient graft vascularisation (n=2), graft necrosis (n= 1) and symptomatic gastric-colic reflux (n=l). RESULTS: The deficient graft irrigation was detected and managed during the surgical procedure in 2 cases, left colonic graft was remplaced by a gastric tube and the right colon, respectively, with excellent results. Repeated endoscopic dilatations (n=4) as well as surgical revision with resection and reanastomosis of the stenotic segment (n=2), did not suffice in children with severe strictures (100%). A second plasty was tried in 2 patients: a failed microsurgical sigmoid graft in one of them, and a presternal esophagocoloplasty with a left colonic graft in the other one. It was impossible to perform a new plasty in two chidren, because of the severe mediastinal fibrosis. One patient was referred with severe gastro-colic reflux and the cologastric anastomosis and the gastrostomy were refashioned. Another patient with graft necrosis required total resection of the coloplasty and a new esophagostomy and gastrostomy. 50% of the patients recovered digestive continuity, and nowadays three of them eat normally. The fourth one died after several years because of an Guillain Barré syndrome. Four patients are still waiting for future attempts of esophageal substitution. CONCLUSIONS: There are surgical options to reestablish the digestive continuity whenever the initial esophageal replacement fails. Severe postoperative strictures do not dissapear with endoscopic dilatations or stenotic resection and reanastomosis, but they usually require a new graft in another less injured place. Poor vascularisation of the graft can be prevented, giving the best solution for each patient, and at minimal suspicion of ischemia, consider another plasty or access during the operation.


Assuntos
Colonoscopia/métodos , Atresia Esofágica/cirurgia , Estenose Esofágica/cirurgia , Esofagoscopia/métodos , Obstrução Intestinal/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos , Falha de Tratamento
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