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J Tovar

Publications and source records attributed to J Tovar.

At least 19 recordsLinked to original sources
PubMed2006

Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity.

Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen- and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 microM). The IC50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 microM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (approximately 40%) in the presence of SNAP (30-150 microM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.

Animals↗
PubMed2005

Intestinal transplantation in children: differences between isolated intestinal and composite grafts.

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.

Adolescent↗
PubMed2004

Characterization of a mitochondrion-like organelle in Cryptosporidium parvum.

Cryptosporidium parvum is a protozoan parasite that causes widespread diarrhoeal disease in humans and other animals and is responsible for large waterborne outbreaks of cryptosporidiosis. Unlike many organisms belonging to the phylum Apicomplexa, such as Plasmodium spp. and Toxoplasma gondii, there is no clinically proven drug treatment against this parasite. Aspects of the basic biology of C. parvum remain poorly understood, including a detailed knowledge of key metabolic pathways, its genome organization and organellar complement. Previous studies have proposed that C. parvum lacks a relic plastid organelle, or 'apicoplast', but that it may possess a mitochondrion. Here we characterize a mitochondrion-like organelle in C. parvum by (i) ultrastructural and morphological description (ii) localization of heterologous mitochondrial chaperonin antibody probes (iii) phylogenetic analysis of genes encoding mitochondrial transport proteins (iv) identification and analysis of mitochondrion-associated gene sequences. Our descriptive morphological analysis was performed by energy-filtering transmission electron microscopy (EFTEM) of C. hominis and C. parvum. The 'mitochondrion-like' organelle was characterized by labelling the structure with a heterologous mitochondrial chaperonin probe (hsp60) both in immunoelectron microscopy (IMEM) and immunofluorescence (IMF). Phylogenetic analysis of the mitochondrial import system and housekeeping components (hsp60 and hsp70-dnaK) suggested that the C. parvum mitochondrion-like organelle is likely to have descended from a common ancestral apicomplexan mitochondrion. We also identified a partial cDNA sequence coding for an alternative oxidase (AOX) gene, a component of the electron transport chain which can act as an alternative to the terminal mitochondrial respiratory complexes III and IV, which has not yet been reported in any other member of this phylum. Degenerate primers developed to identify selected mitochondrial genes failed to identify either cytochrome oxidase subunit I, or cytochrome b. Taken together, our data aim to provide new insights into the characterization of this Cryptosporidium organelle and a logical framework for future functional investigation.

Amino Acid Sequence↗
PubMed2004

[The multifocal hepatic hemangioendothelioma. Is always a benign tumor?].

UNLABELLED: The hepatic multicentric haemangioma is defined by its extension, affecting all the mass of the liver. The high mortality associated with it is mostly related with the complications produced by its enormous size (haemodynamic, platelet trapping, spontaneous rupture and bleeding). There is a general belief that is a benign tumor with possibility of spontaneous regression and cure. AIM: Retrospective analysis of our recent cases of MHH with the purpose of: 1 degrees) To show the evolution and results. 2 degrees) To realize if the "benign character" of the tumor is real or if some cases may be considered as malignant tumors. MATERIAL AND METHODS: 10 cases of MHH treated in the last 10 years. In 9 the age of presentation was less than 6 months and one patient was diagnosed at 3 and half years. The diagnosis was confirmed by image techniques in 7 cases and by biopsy in 3. In 7 patients extrahepatic vascular lesions were associated prior to the treatment. Methylprednisolone was given to all the cases and alpha-2-interferon was administered to the patients that not responded to the steroids. Vincristine was added to 2 patients. In two cases the hepatic artery embolization was tried and one patient had a liver transplant. RESULTS: Four children had at least one episode of congestive cardiac insufficiency, two patients suffered a consumption coagulopathy (Kasabach Merrit syndrome), and one presented acute hepatic failure. In six children it has been complete regression of the tumor, one more is still under treatment and three died. The dead were produced by the malignant behavior of the tumor in one case (tumoral rupture of a MHH recurrence in the transplanted liver), and possibly in other (intracranial haemorrhage and hepatic failure in a liver transplantation candidate without demonstrated extrahepatic extension in the previous studies, but with multiorgan dissemination at autopsy. In both cases it was impossible to discover signs of histologic or biologic malignancy neither in the primitive lesion nor in the metastasis. CONCLUSIONS: 1a) The regression of the MHH, spontaneous or induced by the treatment is frequent. 2a) Some cases of MHH are aggressive and develop local recurrences and distant metastasis. 3a) The discrimination between MHH of "benign" or "malignant" behaviour is not possible. 4a) Despite of the unpredictable biological conduct of the tumor, the liver transplantation must be considered as an option in the symptomatic cases that not respond to the conventional treatment.

Child, Preschool↗
PubMed2004

[Results of an intestinal transplantation program in Spain. Five years later].

BACKGROUND: More than two thirds of all intestinal transplantations (ITx) performed around the world correspondent to recipients younger than 18. OBJECTIVE: To analyze our 5-year experience in pediatric ITx. PATIENTS: We assessed the outcome of the 19 children included in list out of 41 patients considered for ITx from 1997. The main cause of intestinal failure was short bowel syndrome (14) followed by intestinal motility disorders (3) and congenit disorders of intestinal epithelium (CDIE) (2). The median of age, at the moment of including in the list, was 0.9 years (range 0.4-17) and median of weight was 6.4kg (range 0.4-29.3). Ten children were included for liver and small bowel transplantation (LSBTx), 7 to isolated small bowel (SBTx), and 2 for multivisceral transplantation (MVTx). Indications for SBx were hepatic fibrosis/cirrhosis (10), hepatic fibrosis in evolution (5) (to avoid later LSBTx), intractable diarrhoea (1), recurrent line infections (1), lost of central vein access (1), and bad quality of life in one. RESULTS: Five children died in the waiting list, after a median time of 325 days (range 19-581). Seven remain in the waiting list (median 139 days, range 30-778). In 3 of these the indication changed from SBTx to LSBTx because of progression to end stage liver disease. Six children recieved seven grafts (1 MVTx, 4 LSBTx, 2 SBx) after a median time in the waiting list of 352 days (range 66-732). Six out of seven grafts achieved normal function and all survivals reached full digestive autonomy after Tx. We had to rejection episodes, one with good response to medical treatment and one that required removal of intestinal allograft and later LSBTx. Two children died 1 because of problem not related to the procedure (hemorrage following liver biopsy) and one girl died 29 months after transplant due to post-transplantation lymphoproliferative disease. CONCLUSIONS: ITx is a realistic alternative in our country for children with intestinal failure. The main problems are immunologic (rejection, lynphoproliferative and disease) Shortage of small weight donors is a dramatic limitation that prompts the discussion of surgical alternatives.

Adolescent↗
PubMed2003

Pediatric living donor liver transplantation.

AIM: The aim of this study was to analyze the results of living donor in a pediatric liver transplantation program. PATIENTS: Twenty-six living donor liver transplantations were performed in children from 0.5 to 14.8 years of age. The main indication was biliary atresia (72%) followed by tumors (2 hepatoblastomas and 1 hepatocarcinoma). Left lateral segments were used in 23 (1 transformed into a monosegment), 1 left lobe was used in 1, and right lobes were used in 2. Arterial reconstruction employed saphenous venous grafts in the first 3 cases and end-to-end anastomoses with a microsurgical technique in the following 22 cases. RESULTS: There has been no major morbidity in the donors, with a median hospitalization of 6 days. Four grafts have been lost; 2 in the first 3 cases. In only 1 case, the graft loss was related to the procedure saphenous venous graft thrombosis). Early biliary complications were frequent (23%). Six month, 1 year, and 5 year graft and patient survival rates were 91%, 85%, and 85% and 100%, 96%, and 96%, respectively. CONCLUSIONS: Living donor liver transplantation is an excellent option for transplantation in children.

Adolescent↗
PubMed2003

Pediatric intestinal transplantation.

AIM: Analyze the results of a paediatric intestinal transplantation (IT) program in Spain. PATIENTS: During an 5-year period, 18 children were included as candidates for IT. The causes for intestinal failure (IF) were short bowel syndrome (n=13), motility disorders (n=3), and congenital epithelial disorders (n=2). Nine children were admitted for a combined liver-small bowel transplant (LSBT), seven for an isolated intestinal transplantation (IIT) and two for a multivisceral transplantation (MVT). In three of the candidates for IIT the indication had to be changed to LSBT because of progression of the liver damage. RESULTS: Eight candidates are on the waiting list: four for LSBT, two for IIT, and two for MVT. Four children died before transplantation. All were children under 1 year and candidates for LSBT. One child died during an attempted MVT. Five children underwent transplantation. Grafts were IIT in two and LSBT in three. Of these children, two are on a normal diet (respective follow-up times: 40 and 18 months), two died, both with functioning liver and intestinal grafts (hemorrage after liver biopsy and lymphoproliferative disease), and one developed an untreatable rejection that lead to loss of the intestinal graft; currently, she is on the waiting list for LSBT. CONCLUSIONS: The morbidity and mortality of IT are high, but it is the only possible treatment for children in IF who cannot be adequately managed with parenteral nutrition. A severe problem is the the scarcity of suitable donors for the very low weight children who are candidates for LSBT.

Adolescent↗
PubMed2003

[Activity of a pediatric intestinal transplantation program in Spain].

AIM: To analyze the outcome of children with intestinal failure (IF) included as candidates for intestinal transplantation (IT). Patients, Eight out of 23 children with IF assessed since July 1997 met criteria for IT and were included on the waiting list. The causes of IT were Short Bowel Syndrome (SBS) in 6 and Microvillus Inclusion Disease (MID) in 2. The indication of IT were end stage liver disease (ESLD) in 5 (related to total parenteral nutrition administration, TPN), progressive hepatic fibrosis in 2 and loss of venous access in 1. The patients with ESLD were included for combined liver-small bowel transplantation (LSBT) and the remaining for isolated intestinal transplantation (IIT). RESULTS: Two children died waiting for LSBT, 4 patients are on the waiting list, 2 for LSBT and 2 for IIT (length of stay: 4-11 months). Two children were transplanted, one with IIT in a 2.5 years old boy with MID, and one with LSBT in a 22 months girl with SBS and ESLD. Both patients recovered intestinal function after transplantation and are a live (follow-up of 19 and 10 months respectively). The LSBT's patient is under treatment for postransplant lymphoproliferative disease (PTLD). CONCLUSIONS: The lack of suitable donors for the small children candidate to IT explains the long period of stay on the waiting list and the high pretransplant mortality. Two strategies are possible; early referral of children with IF to a transplant center and surgical techniques like ex vivi-hepatic reductions of the LSB graft.

Child↗
PubMed2003

[Prognostic factors in pediatric liver transplantation. Multivariate analysis].

AIM: To analyze independent risk factors associated with poor graft and patient survival in a series of 292 pediatric liver transplants (PLT) performed in 234 children during a 15 years period. MATERIAL AND METHODS. 1. Univariate graft and patient survival analysis in 45 variables related to pretransplant patient status, surgical technique and donor conditions. 2. Variables found with univariate analysis to be associated with outcome were entered into a stepwise backward proportional hazard model (Cox), to determine independent prediction of outcome. RESULTS: 11 variables influence the graft survival: recipient age, z-score recipient height, UNOS status, recipient and donor weight, transplant for immune hepatitis, platelet transfusion during the transplant, blood index > 4 during the surgery, type of arterial reconstruction, retransplantation and era of the transplant (first er: 1986-1990; 2nd. era: 1991-1995; 3rd. era: 1996-2000). Four of those variables are independent in the multivariate analysis: UNOS 1 status (Odds Ratio, OR = 2.82, 95% confidence interval = 1.36-5.85), recipient < 3 years (OR = 3.76, 95% CI = 2.13-6.63), transplants for autoimmune hepatitis and era (OR of first and second versus third era respectively 3.93 and 2.81). The independent variables influencing the patient survival were: children receiving more than one graft children less than 3 years old and transplant era. CONCLUSIONS: Liver transplant in small children is associated with an increased risk of graft loss and patient dead. The experience of the hospital in pediatric liver transplantation improves the results, particularly in small children.

Adolescent↗
PubMed2002

[Mesenteric-cava shunt's results with autologous jugular vein graft in children with pre-sinusoidal portal hypertension].

UNLABELLED: Presinusoidal portal hypertension (PPH) in children evaluates without functional hepatic damage, and with the time, trends to compensate through the creation of spontaneous portosystemic shunts. Nevertheless, some patients suffer episodes of gastrointestinal bleeding (GIB) that because of its frequency or severity, force to propose the change of surgical treatment. AIM: To evaluate the results of the mesocaval shunt (MCS) with autologous jugular vein in children with PPH. MATERIAL AND METHODS: Among the 32 children with PPH treated in our Hospital in the last 7 years, 10 had episodes of GIB that forced to perform a surgical shunt. The types of shunt were distal splenorenal in 3 patients and mesocaval in 7. These 7 cases are the material of this study. The origin of the PPH was a cavernomatosis transformation of the portal vein in 6 cases and a congenital hepatic fibrosis in 1. Before the surgery the average number of episodes of GIB was 9 (range 2-15); all the patients needed transfusion of blood products and variceal sclerosis. In 2 cases a tamponade with the Sengtaken balloon was required and 5 patients were treated with somatostatin and propranolol. The Doppler ultrasounds revealed and intense hepatofugal collateral circulation in all the cases. RESULTS: The initial flow through the shunt was adequate in all the patients except one who required a percutaneous balloon dilatation. Only this patient has suffered an episode of GIB. The hyperesplenism signs disappeared or improved in all the seven cases and the collateral circulation was significantly reduced. The pressure in the splenic territory decreased around 50% in the 4 patients that was measured. There were no cases of encephalopasty and only one child with congenital hepatic fibrosis shows signs of mild hepatic disfunction. The medium follow up post-shunt is 32 months (range 8 m-6 years). CONCLUSIONS: The MCS prevents the GIB in the PPH not responsive to the conservative treatment; its effectiveness is related with an adequate permeability though the graft and at least in the cases with portal cavernomatosis (the most frequent in children) doesn't produce hepatic dysfunction. Doppler ultrasounds give a very precise information about the post-surgical situation and are an excellent method of follow up.

Child↗
PubMed2001

[Intestinal transplantation. First experience in Spain].

UNLABELLED: We present the first case of intestinal transplant (IT) performed in Spacin. CASE REPORT: 28 months old boy with secretory diarrhea since the first month of life, diagnosed of microvillous inclusion disease (MID). He is on total parenteral nutrition (TPN) and had suffered of multiple episodes of catheter related sepsis with lost of standard venous access. An isolated small bowel transplant from a cadaveric donor was performed at the age of 3 years. The native ileocaecal valve and colon were not removed. RESULTS: Enteral feeding was started in the 2nd. week after the IT. On the 25th day he was off TPN. Since the 77th day, he eats regular foods by mouth. At the 6th month post IT the ileostomy was closed. Among the complications, he suffered a rotavirus infection on the 38th post IT day and an episode of mild rejection responsive to methil-prednisolone bolus. CONCLUSIONS: The IT is a therapeutic option that can be already offered with possibilities of success in our country. Although the colonic enterocytes express MVD, the recipient ileocaecal valve and colon can be preserved.

Child, Preschool↗
PubMed2001

[Prognosis in children with biliary atresia successfully treated with Kasai's operation].

BACKGROUND: The Kasai procedure, portoenteroanastomosis (PEA) didn't reach international spreading until the seventy's decade, making difficult to find long-term results from children with ABE successfully treated with this technique. At our institution in the last fifteen years all the therapeutics procedures for these patients can be offered, including the liver transplant. AIM: To show the evolution of our patients with ABE treated with the PEA and that survive long-term without being transplanted. METHODS: The clinical course of 22 patients that survive more than 10 years after the PEA with their own liver is reviewed. The hepatic survival indexes of (success, death or transplant) are beyond the tenth year. The problems raised during the follow-up are analysed. RESULTS: From 99 patients with ABE treated primarily in our center, 22 reached the 10 year-old age after the PEA without a liver transplant. In the follow-up, seven if the these finally needed the transplant. Their median age was 12.2 year-old (range: 10.5-13.8) for a progressive hepatocellular damage in 5 cases associated to syndrome hepatopulmonar in two cases. The other fifteen patients have a compensated hepatopathy. Five of them do not have hyperesplenisme and the serum bilirrubine levels are lower than 1.3 mg/dL. The medium age of these patients at the end of the follow-up was 14.8 years. CONCLUSIONS: In spite of the reestablishment of the biliary flow with the PEA, few are the patients with ABE that preserve their hepatic function lapsed long periods of time. Nevertheless the prognosis of these patients is excellent.

Adolescent↗
PubMed2001

[Liver transplantation in infants younger than one year of age].

BACKGROUND: The development of the surgical techniques of hepatic division has maken that the young age (less than one year old) is no longer considered a risk factor in the pediatric liver transplant (TH). AIM: To show our experience with the TH in children younger than one year, comparing these results with the rest of the series and in second place to analyze if a bigger experience improves the results of the TH in this group of patients. METHODS: 44 patients that received a TH with less than a year of age are reviewed. Among them, 27 were in the last five years. The survival indexes of the graft and the patient are determined at 1, 5 and 10 years comparing them with three rest of the series. RESULTS: The grafts and patients survival was slightly inferior in the less than one year old, although in the last five years it improved 71.4% vs 82.1% at one year follow-up, and 61.9 in front of 74.5% at five years. The clinical situation of the patients that were transplanted before the year of life was worse: 43% (UNOS III, IV) in front of 13.1% in the same stadiums in the rest of the serie. In the younger patients, 54% of the grafts were reduced, versus 21% in the older. There were not a higher rate of complications in the young group. CONCLUSIONS: In spite of the difficulties of the TH in children younger than one year of age, the results are not very different from those obtained in the rest of the patients. In these results the experience of the transplant center have a great influence.

Humans↗
PubMed2001

[Pre-hepatic portal hypertension as a late complication of liver transplantation in children].

UNLABELLED: In the long-term after liver transplantation (LT), some children develop prehepatic portal hypertension (PPH) and raise problems not very well known yet; many of the lessons learned with the management of these patients may be useful outside the LT. AIM: 1. To analyze the incidence and risk factors of PPH after LT. 2. To evaluate the results with the different treatments used. METHODS: Retrospective study over 164 children surviving more than 1 year after LT. Univariant analysis of possible risk factors associated and multivariant (logistic regression), for those that had significance in the univariant analysis. Other factors associated are analyzed as well as the indications and results of two types of treatment: percutaneous pneumatic dilatation and surgical shunt (splenorenal and Rex shunt). RESULTS: 9 children developed symptomatic PPH (hemorrhage in 8, ascites in 1), associated to lymphoproliferative post-LT disease in 2, and to anastomotic biliary stricture in 1. The age at first LT (children under 1 year old), weight (below 10 kg), and need of retransplantation (reLT) were in the univariant analysis the associated variables with increased risk of PPH. The diagnosis (biliary atresia) and the emergency status of the LT were almost significative. In the multivariant analysis, the need of reLT is the only independent variable that increases the risk (relative risk: 4.5, confidence interval 95%: 1.29-18.87). At diagnosis 3 cases showed portal estenosis, and 5 showed absence of permeability with cavernomatous transformation. The PPH was caused in one case because of the esplenic vein disconnection (treatment not required at the moment); the three cases of portal estenosis were dilated percutaneously with success, and 2 of the 5 cases with portal thrombosis have been surgically shunted: one by an splenorenal shunt and the other by a Rex shunt (first case done in Spain); the other 3 cases are stable waiting for a surgical solution. The hepatic function is normal in the 9 cases. CONCLUSIONS: The PPH can complicate the prognostic of the pediatric LT in the long term. The treatment depends on the permeability of the portal trunk. Whenever possible, percutaneous dilatation should be attempted; should surgery be required, the Rex shunt is the best option.

Child↗