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V Bueno

Publications and source records attributed to V Bueno.

At least 19 recordsLinked to original sources
PubMed2004

FTY720 impairs necrosis development after ischemia-reperfusion injury.

Ischemia-reperfusion (IR) injury is a common early feature that contributes to graft damage by impairing resident cell function. Our previous results showed that IR injury impaired renal function, by causing extensive tubular necrosis and increasing MHC class II and ICAM-1 molecule expression by mesangial cells (MC). MCs are likely candidates to come into close contact with immune cells such as monocytes or lymphocytes. It has been suggested that under inflammatory circumstances, there is increased MC expression of MHC class II, of adhesion molecules (such as ICAM-1), of cytokines receptors, and of molecules associated with cellular death (apoptosis). The immunosuppressive properties of FTY720 have been shown in clinical and experimental situations. It has also been shown to be protective against IR injury in rats. We sought to evaluate the role of FTY720 in a murine IR model by measuring renal function, tubular necrosis, and surface molecule expression by cultured mesangial cells. Intravenous administration of FTY720 (1 mg/kg) immediately before IR induction did not improve the short-term (24 hours) outcome of renal function or reduced MHC class II and ICAM-1 surface molecule expression. However, there was a decreased percentage of tubular necrosis in mice treated with FTY720 (51.3% +/- 1.6%) compared with vehicle-treated mice (66% +/- 5.5%). These results suggest a protective role of FTY720 in an IR injury model. More studies are required to identify the mechanisms involved in the protective activity of FTY720 in the IR injury model.

Analysis of Variance↗
PubMed2004

FTY720 treatment prolongs skin graft survival in a completely incompatible strain combination.

FTY720 has shown potent immunomodulatory activity in a variety of animal organ transplant models. However, the in vivo immunosuppressive mechanism of FTY720 is still not fully understood. It has been suggested that the marked decrease in the number of peripheral blood lymphocytes during FTY720 administration could be responsible for its immunosuppressive effects. Our aims were: (1) to study the effects of FTY720 treatment on skin graft survival using a fully mismatched strain combination and (2) to evaluate lymphocyte numbers in different sites at 5 days after skin transplant. C57BL/6 mice and BALB/c mice were the donors and recipients respectively. BALB/c mice received FTY720 (1 mg/kg/d) orally for 4 consecutive days. Drug administration started 1 day before skin transplants. A small segment of tail skin was affixed on the right dorsal side of the mouse via sutures. The administration of FTY720 (4 mg/kg) prolonged skin graft survival from 12.6 +/- 2.2 days (no treatment) to 16.6 +/- 4.2 days. The histologic findings of rejection were similar for all groups. Five days after transplant, lymphocyte numbers were significantly increased in lymph nodes compared with nontransplanted or isogenic graft mice. FTY720 decreased lymphocyte numbers only in the spleen. In conclusion, FTY720 prolonged skin graft survival in a fully mismatched strain combination when administered for 4 days (day -1 to day +2) at a dose of 1 mg/kg/d. The decreased number of lymphocytes in the spleen suggests that the spleen may be a target of FTY720 activity, during the early posttransplant period.

Animals↗
PubMed2004

Microchimerism does not correlate with survival of murine cardiac allografts.

The development of microchimerism was evaluated at different time points after infusion of a mixed population of bone marrow and spleen cells from (BALB/c x C57Bl/6)F1 mice in the presence or absence of a cardiac transplant. Microchimerism was observed in the spleen, bone marrow and thymus of transplanted BALB/c mice even after graft rejection. In the absence of transplantation, donor cells persisted especially in the thymus. The results show that despite augmentation of graft survival after donor cell infusion compared to nontreated controls, the development of microchimerism did not sustain cardiac semihistocompatible grafts. Moreover, the persistence of donor cells in the thymus in both situations suggests a role for this organ in the increased graft survival in our model.

Animals↗
PubMed2004

N-Domain angiotensin I-converting enzyme expression in renal artery of Wistar, Wistar Kyoto, and spontaneously hypertensive rats.

One of the most intriguing features in kidney transplantation is the finding that kidneys from hypertensive rats can transfer arterial hypertension on transplantation into normotensive rats. Some evidence also suggest that, in humans undergoing renal transplantation, the genotype of the donor kidney determines the blood pressure in the recipient. The renin-angiotensin-aldosterone system is the major etiological candidate in hypertension because it plays an important role in the control of cardiovascular homeostasis. Angiotensin-converting enzyme (ACE) cleaves the C-terminal from angiotensin I as well as from bradykinin. Thus, by generating the potent vasoconstrictor angiotensin II and by degrading the vasodepressor bradykinin, ACE is considered to play a role in blood pressure regulation. We have previously described the presence of N-domain ACE in urine of Wistar (W), Wistar Kyoto (WKY), and spontaneously hypertensive rats (SHR), all of which can hydrolyze the vasodilator peptide Angiotensin 1-7 and also the N-Acetyl-Ser-Asp-Lys-Pro, two peptides described as specific for N-domain ACE. These findings suggest that the 90 kd ACE isoform found in urine and in tissues of SHR is a possible genetic marker of hypertension. Based on the fact that the renal artery has an important role in the control of renal blood flow, we evaluated the presence of N-domain ACE in the renal artery of hypertensive and normotensive rats. Using Western blotting techniques on the renal arteries of W and WKY rats, we detected the 190-kd ACE (similar to somatic ACE) and also the 65-kd ACE previously described in urine and renal tissue as N-domain ACE. The 65-kd and 90-kd isoforms of ACE were also detected in renal arteries in SHR rats. Further studies are required to understand the role of 90-kd enzyme described as a possible local marker of hypertension, its contribution in angiotensin catabolism, and whether this abnormal form of the enzyme has any link with the development and transfer of hypertension after transplantation.

Angiotensin I↗
PubMed2003

[Apolipoprotein E polymorphism as a predictor of progression of multiple sclerosis].

INTRODUCTION: During recent years, different studies have proposed that apolipoprotein E e4 can be a predictor of progression in multiple sclerosis. We aim to evaluate these findings in our country. PATIENTS AND METHODS: We studied 42 patients with relapsing remitting or secondary progressive multiple sclerosis, and a disease duration of at least 2 years. We correlated the presence or absence of e4 allele with markers of progression such as age of onset and diagnosis, disease duration, number of relapses, EDSS at 1, 2, 5 and 10 years, progression index and relapse rate. RESULTS: None of the parameters evaluated significantly correlate with e4 allele of the APOE. CONCLUSIONS: In spite of the limitation due to the small number of patients studied, we cannot confirm that APOE e4 allele is a predictor of progression of disability in multiple sclerosis.

Adult↗
PubMed2002

The role of CD8+ T cells during allograft rejection.

Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.

Animals↗
PubMed2000

[Prospective epidemiologic study of headache in ambulatory neurology service in the province of Palencia].

OBJECTIVES: To study demographic data about the first time consultations for headache in our neurologic clinic, its diagnostic distribution, its diagnostic and therapeutic management by the neurologist, its source, and the influence of the primary care doctors formation in their search of neurological consultation and therapeutic management in patients with headache. PATIENTS AND METHODS: A protocol with several demographic clinical and medical care data of the all first time visits for headache in our province was picked up, during 3 consecutive months. RESULTS: Headaches represent 21.5% of the first time consultations. The majority of the patients were women. The primary care doctors sent 93.6% of patients. The two more common diagnoses were tension-type headache (60%) and migraine (25.4%), reflecting their prevalences in the population. The more common treatments were the associations of two drugs. The general doctors sent more patients with headache (3.36 per thousand and year) than family doctors (1.84 per thousand and year). The approximation between initial diagnosis (primary care doctor) and final diagnosis (neurologist) was 26.4%, greater for family doctors (38.1%) than for general doctors (23.9%). CONCLUSIONS: Headaches represent the first cause of neurological consultation. The diagnostic distribution of the patients sent to our province shows the prevalences in the population. The family medicine formation is useful for a better selection of the patients sent to neurologists and a better diagnostic approach.

Adolescent↗
PubMed1996

[Stroke and hematological disorders in young people].

In this work we analyse the information about one group of young patients with cerebrovascular disease, studying the association between haematological pathology and cerebrovascular disease. The objective is to establish a comparison between our results and those previously reported in the medical literature.

Adult↗
PubMedDate not supplied

FTY720 prevents renal T-cell infiltration after ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.

Animals↗
PubMedDate not supplied

Prolonged administration of FTY720 does not cause renal toxicity in mice.

Prevention of allograft rejection without renal toxicity caused by calcineurin-inhibitor immunosuppression is a major goal for transplantation. FTY720 is a synthetic drug that modulates immune responses of transplantation in many animal models. FTY720 modulating mechanisms relate to lymphocyte migration to peripheral lymph nodes instead of inflammatory sites. The drug has no effect on T-cell proliferation or cytokine production, and therefore prevents generalized immunosuppression. However, it is still to be confirmed that FTY720 has no nephrotoxic effects when administered continuously. In the present study FTY720 was administered orally for 21 days to C57BL/6 mice that underwent weekly evaluations. FTY720 (1 mg/kg per day) impaired body weight gain, but had no significant effect on either renal function or structure. Our findings suggest that FTY720 may provide a reasonable add-on therapy in calcineurin-inhibitor-treated transplant recipients.

Animals↗
PubMedDate not supplied

[Semiquantitative evaluation of cranial computerized tomography as diagnostic support in progressive supranuclear palsy].

INTRODUCTION AND OBJECTIVES: Different neuroimaging findings have been described in association with progressive supranuclear palsy (PSP), but their use as diagnostic support in this condition has been the subject of much discussion. PATIENTS AND METHODS: Three radiologists, non-specialists in neuroradiology and with no specific information regarding neuroimaging in Parkinson syndromes, analyzed (without knowing any clinical details) seven cranial CT in five patients diagnosed as probable PSP according to NINDS-SPSS criteria, nine with idiopathic Parkinson's disease, and six persons aged over 55 years who acted as controls. The radiologists were asked to assess 17 variables as absent, moderate or severe. The results were analyzed using the chi squared test for qualitative variables and Fisher's exact test when necessary. RESULTS: The identification of the variables antero-posterior and transversal atrophy of the mid-brain, atrophy of the pons, enlargement of the perimesencephalic cisterns and the quadrigeminal plate and increased size of the third ventricle were considered to be statistically significant in the cases of PSP as compared with other observations. The small number of patients did not permit the establishment of correlation of statistical importance between the radiological parameters and clinical condition. CONCLUSIONS: We present the point of view of non-specialist neuroimaging workers, in these patients. We found that there were six parameters of interest on cranial CT which permitted differentiation of cases of PSP, idiopathic Parkinson's disease and a control population. Four of these parameters did not appear to a severe degree in patients who did not have PSP. These results are partly comparable to those published in the literature.

Aged↗
PubMedDate not supplied

[Pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation].

Pharmacokinetics of cyclosporine shows high inter and intra-individual variability and changes in several parameters are often found after kidney transplantation. PURPOSE--Evaluate serial studies of the pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation. METHODS--The pharmacokinetics of cyclosporine and its metabolites were analyzed in 70 studies performed in 29 patients, 26 before and 44 after kidney transplantation. The blood cyclosporine concentration was determined in 17 samples obtained after is oral or intravenous administration, using radioimmunoassay with specific (RIE-MoSP) and nonspecific (RIE-MoNP) monoclonal antibodies. RESULTS--The values of area-under-the-time-concentration curve (AUC), bioavailability (F), peak concentration (Cmax) and the 12 and 24 trough levels (C12 and C24), determined with RIE-MoSP, were lower than that obtained with RIE-MoNP, and the clearance (CL) and the volume of distribution (Vd) were higher. The elimination half-lives (t1/2) for both methods were not different. The absorption followed a zero order kinetic, demonstrating an inverse correlation between cyclosporine dose (mg/kg) and AUC/dose (r = -0.55, RIE-MoSP and r = -0.42, RIE-MoNP). Bioavailability ranged between 18% and 68% (RIE-MoSP) and were overestimated when calculated using RIE-MoNP (38% to 100%) owing to extensive cyclosporine metabolization during the first passage through the intestine and the liver. The metabolic rate analyzed by the ratio of blood concentrations determined with RIE-MoNP and RIE-MoSP (NP/SP), increased during the first 12 hours after cyclosporine administration, and was higher after oral dosing. The hematocrit and the serum lipoproteins concentrations significantly correlated with several pharmacokinetics parameters, mainly when they were determined with RIE-MoSP. The correlation between one sample obtained at any time after cyclosporine administration and the AUC were unsatisfactory, even the trough levels of 12 and 24 hours. AUCs calculated with 3 selected samples chosen by multiple linear regression correlated with AUC calculated using 17 samples, with a determination coefficient higher than 0.95 (RIE-MoSP, r = 0.975; RIE-MoNP, r = 0.974). CONCLUSION--Among all the parameters calculated, parameters of total exposure to the drug (AUC, AUC/dose, Cssav) showed the best correlation with the dose of cyclosporine, hematocrit and serum lipoproteins concentration. The methodology simplification, reducing the number of samples to calculate AUC, could be a good strategy to apply routinely these parameters in clinical transplantation.

Adolescent↗