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J Segovia

Publications and source records attributed to J Segovia.

At least 19 recordsLinked to original sources
PubMed2005

Modification of dopaminergic markers expression in the striatum by neonatal exposure to glutamate during development.

Monosodium l-glutamate (MSG) was administered subcutaneously to male neonatal rats, and the effect on developmental profile of tyrosine hydroxylase (TH), D1, D2 receptors, and dopamine (DA) transporter expression in the striatum was examined using Western blot. In addition, TH-immunopositive neurons at substantia nigra (SN) were also examined. MSG treatment (4mg/g of body weight, administered on postnatal days 1, 3, 5, and 7) resulted in a reduction of D1 and D2 receptor expression from 30 days of age and persisted to adulthood (120 days of age), while DA transporter expression was significantly reduced from 14 days of age to adulthood. TH immunopositive neurons at SN showed a significant reduction, as well as TH expression on postnatal days 10, 30, 60, and 120 at striatum was reduced. No changes of TH were observed at 14 days of age. Results indicate that an over-stimulation of the glutamatergic system by neonatal exposure to a high glutamate concentration induces a partial loss in TH-positive neurons in the SN and an important reduction in dopaminergic markers expression in the striatum, suggesting that early excitotoxicity could contribute to developmental alterations in the nigrostriatal pathway, which may be associated with various disorders of the basal ganglia.

Aging↗
PubMed2003

Differential characteristics of heart transplantation in patients older than 60 years.

BACKGROUND: The effect of advanced age on the results of heart transplantation (HTx) is still controversial. The few articles addressing this issue have not been conclusive, due to either short follow-up periods or small numbers of patients. METHODS: We present a retrospective study of 560 HTx which were divided into group A, including patients of 60 or less years at HTx (n=465, 83%), and group B, of 95 recipients older than 60 years. A subgroup of the latter, named B1, includes 24 patients older than 65. More than 100 recipient, donor and surgical procedure variables were analyzed for their impact on actuarial survival and incidence of common causes of posttransplant morbidity and mortality during a follow-up period longer than 10 years. RESULTS: Group B showed a lower number of acute rejection episodes than group A, (1.53+/-1.87 versus 1.96+/-1.81, P<.04). Both groups showed a similar incidence of infection episodes, malignancies or graft vasculopathy, but older patients experienced fewer viral infections than younger ones (9% in group A versus 18% in group B, P<.05). Log-rank test showed a trend to shorter survival in group B (P=.08), a disadvantage that reached significance (P=.01) among patients older than 65 years. CONCLUSIONS: Patients who were older than 60 at HTx displayed a lower incidence of acute rejection episodes and viral infections, but a trend toward shorter long-term survival. This disadvantage in prognosis was statistically significant among recipients older than 65 years.

Actuarial Analysis↗
PubMed2003

Pulmonary nocardiosis in heart transplant recipients: treatment and outcome.

BACKGROUND: Nocardial infections typically affect patients receiving immunosuppressants, occurring early after surgery in 3% to 40% of heart transplant (HTx) recipients. The emergence of antibiotic resistance and occurrence of disease recurrences in AIDS population has engendered controversy about the treatment for immunodepressed HTx patients. METHODS: We present a retrospective study of the diagnosis, treatment and outcome of 560 HTx recipients between 1984 and 2002. RESULTS: Among the five cases of Nocardia infection (0.9%), three cases developed late after HTx (between 3.1 and 11 years follow-up). All patients had pulmonary disease and one in addition had subcutaneous nodules. Microbiological diagnosis required open lung biopsy in one case. All patients were treated primarily with trimethoprim-sulphamethoxazole, but evidence of resistance to sulfonamides led us to change the antimicrobial combination in two cases. Four patients who received one year of antibiogram-guided therapy showed complete healing without recidivism. Three patients died, all due to non-related causes, at follow-ups between 1 and 5 years. In one case a cutaneous recurrence of disease was attributed to noncompliance. CONCLUSIONS: Nocardiosis in current HTx is less common than previously reported. Its incidence seems to be delayed in time with modern immunosuppressants. Given the high incidence of sulfamide resistance, treatment must be guided by antibiotic sensitivity. We believe that maintenance therapy for a whole year is the appropriate option in order to avoid recidivism in this population.

Anti-Bacterial Agents↗
PubMed2003

Current induction immunosuppression and post-heart transplant lymphoproliferative disorders.

BACKGROUND: The use of high-dose OKT3 has been reported to be associated with a high incidence of posttransplant lymphoproliferative disorders (PTLD) in heart transplantation (HTx) recipients. The incidence and characteristics of PTLD with current induction protocols remain largely unknown. The aim of our study was to analyze the incidence and characteristics of PTLD in a large series of HTx recipients treated with low-dose OKT3 induction. METHODS: From 1984 to 2002, a retrospective review of diagnosis, treatment, and evolution of PTLD cases was performed on the 560 patients who underwent HTx in our center. RESULTS: The incidence of PTLD was 1% (6/560). The disease occurred early after HTx in two cases and between 13 and 121 months in the other four. Molecular studies showed evidence of Epstein-Barr virus (EBV) infection in four patients. B-cell proliferation was observed in five cases, and T-cell proliferation in the other one. Various therapies were employed for each patient. Ganciclovir and reduction in immunosuppression were the most common measures. Interestingly, OKT3 was used as a specific anti-T-cell proliferation agent with some success in the one case of T-cell PTLD. Complete remission was achieved in just two patients, whereas the other four (67%) died, mostly due to other conditions. CONCLUSIONS: The use of low-dose OKT3 as induction therapy did not increase the incidence of PTLD in our series. Late appearance of disease prevailed among our patients. Despite a multidisciplinary approach to therapy, including the use of OKT3 against T-cell proliferation, the mortality rate was high (67%).

Adult↗
PubMed2003

High incidence of severe infections in heart transplant recipients receiving tacrolimus.

BACKGROUND: Tacrolimus (FK) is being increasingly used as an alternative to cyclosporine (CyA) in heart transplantation (HTx). It is believed to engender slightly more powerful protection against acute rejection. However, the increased immunosuppression could result in an excess of infectious complications. METHODS: Our study compared the incidence of major infections (MInf), defined as life-threatening infectious episodes requiring admission and intravenous (IV) antimicrobial therapy, among a series of HTx recipients treated with either FK (n=30) or CyA (n=84). RESULTS: A total of 21 patients received FK in an elective protocol and 9 patients initially treated with CyA were converted to FK. Tacrolimus was combined with azathioprine and prednisone in 21 cases, and with mycophenolate mofetil and steroids in 8 recipients. After a follow-up between 6 and 37 months, 11 patients (37%) in the FK group developed 13 episodes of MInf, most (85%) occurring during the first posttransplant year. Conversely, CyA patients (n=84), a group with similar characteristics and follow-up, showed a MInf incidence of 12% (P<.05). Among the FK group, the most common site of MInf was pulmonary (69%). A variety of opportunistic agents caused MInf in 54% of cases, whereas the remaining ones were attributed to nosocomial bacteria. There were three deaths (27% of all MInf), all in azathioprine-treated patients with initial FK therapy. CONCLUSIONS: Tacrolimus therapy seems to be associated with an increased incidence of severe infections in HTx recipients. We recommend aggressive diagnostic and therapeutic approaches for patients on FK who develop signs or symptoms of infection in the first year after HTx.

Aged↗
PubMed2003

Rapamycin in lung transplantation: preliminary results.

INTRODUCTION: Rapamycin is a potent immunosuppressive agent with a different mechanism of action and different adverse effects from those of calcineurin inhibitors (CNIs). OBJECTIVE: To analyze our experience with rapamycin in patients undergoing lung transplantation and heart-lung transplantation in our center. PATIENTS AND METHODS: Patients were treated with rapamycin when showing chronic rejection and/or toxicity associated with the CNI after lung transplantation or heartlung transplantation. Patients with chronic rejection were administered rapamycin in combination with CNIs, whereas the CNIs were eliminated in patients with toxicity. RESULTS: Since October 2001, 7 patients (4 women), of mean age 45+/-15 years, received treatment with rapamycin (heart-lung transplantation, 2 cases; lung transplantation, 5 cases). The indications were chronic rejection in 4 patients and CMIs toxicity in 3 patients (kidney failure in 2 cases and optic neuropathy in 1 case). Pulmonary function stabilization was observed in 3 of 4 patients receiving rapamycin for chronic rejection. In the 3 patients with CNIs toxicity elimination of these drugs did not result in pulmonary functional deterioration. Patients with kidney failure showed an improvement in creatinine levels; visual acuity improved in the patient with optic neuropathy. We observed 2 infectious complications (pneumococcal pneumonia and pulmonary aspergillosis), which resolved with treatment. CONCLUSION: Rapamycin is an alternative for lung-transplant recipients who develop chronic rejection and/or CNIs toxicity.

Adult↗
PubMed2003

Left atrial thrombosis after heart transplantation.

Left atrial thrombosis in the absence of rheumatic heart disease and atrial fibrillation is a rare occurrence. We report two cases of left atrial pedunculated thrombus formation after orthotopic heart transplantation. Despite an uneventful post-operative course, sinus rhythm and normal contractility of the heart, large thrombi could be found several months following transplantation. Surgical thrombectomy was performed under cardiopulmonary bypass. Operative technique is proposed as one of the main factors that can contribute to left atrial thrombosis after heart transplantation.

Cardiomyopathy, Dilated↗
PubMed2001

Comparative analysis of superoxide dismutase activity between acute pharmacological models and a transgenic mouse model of Huntington's disease.

We examined the activity of striatal superoxide dismutase (SOD) in two acute pharmacological models of Huntington's disease (HD), and compared it with SOD activity in the striata of mice transgenic for the HD mutation. Total SOD, and Cu/ZnSOD activities increased in young transgenic mice, but decreased in older (35 week) mice. We consider that the increased enzyme activity represents a compensatory mechanism to protect cells from free radical-induced damage, but the system becomes insufficient in older animals. Major decreases in SOD activity were also observed both after quinolinic acid and 3-nitropropionic acid intrastriatal injections. The present results indicate that in both types of HD models striatal oxidative damage occurs, and that it is associated with alterations in the cellular antioxidant system.

Animals↗
PubMed2000

Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington's disease.

We examined the degree of oxidative damage to the brain of mice transgenic for the mutation responsible for Huntington's disease. We found that there is a progressive increase in striatal lipid peroxidation (LP), that parallels the worsening of the neurological phenotype. We consider that these transgenic mice may provide an interesting system to test treatments aimed at protecting cells from damage induced by free radicals.

Animals↗
PubMed2000

Primary astrocytes retrovirally transduced with a tyrosine hydroxylase transgene driven by a glial-specific promoter elicit behavioral recovery in experimental parkinsonism.

We used a retroviral-mediated gene transfer system to transduce primary rat astrocytes with a transgene in which the activity of a tyrosine hydroxylase (TH) cDNA is under the transcriptional control of a human promoter of the glial fibrillary acidic protein (GFAP). The engineered cells were tested for their therapeutic efficacy in a rodent model of Parkinson's disease (PD). The method is based both on the properties of astrocytes, as well as on those of the promoter. Astrocytes are an integral part of the neural tissue, have a long life span, are more resistant to oxidative stress than neurons, and possess an efficient secretory system. The GFAP promoter is active throughout postnatal life, and its activity is up-regulated by many insults to the brain, including PD. Transduced astrocytes were implanted into the striata of rats lesioned with 6-hydroxydopamine (6-OHDA), and the efficacy of grafted cells tested. Implanted astrocytes induced a significant reduction in the turning behavior that occurs in response to apomorphine for at least 4 weeks after grafting, and transgenic mRNA and protein could be detected in implanted brains. These results indicate that the gFa2-TH construct can be readily adapted to be used with a retroviral gene transfer system to obtain nontumorigenic cells that sustain a sufficient level of transgene activity to enable therapeutic effectiveness for prolonged periods. These results further endorse the use of astrocytes for gene therapy in the central nervous system.

Animals↗
PubMed1999

Gene therapy in a rodent model of Parkinson's disease using differentiated C6 cells expressing a GFAP-tyrosine hydroxylase transgene.

Cells expressing a tyrosine hydroxylase (TH) cDNA under control of the promoter of the human glial fibrillary acidic protein (GFAP) gene were tested for therapeutic efficacy in a rat model of Parkinson's disease. The GFAP gene encodes an intermediate filament protein found almost exclusively in astrocytes. Its promoter is of interest for gene therapy as it is expressed in astrocytes throughout postnatal life and is upregulated in response to almost any damage to the central nervous system, including Parkinson's disease. We previously showed that a line of C6 rat glioma cells that expresses a GFAP-TH transgene, C6-THA, displays increased transgene activity when differentiated by forskolin treatment. Accordingly, the effects were investigated of implantation of both undifferentiated and differentiated C6-THA cells into the striatum of rats that had been lesioned with 6-hydroxydopamine. Implantation of either cell type produced significant behavioral recovery one week after transplantation, as judged by the turning response to apomorphine. At two and three weeks after transplantation, the behavioral effect of the undifferentiated cells was no longer statistically significant, whereas that for the forskolin-differentiated cells remained robust. Transgenic TH mRNA and protein could be detected in implants of both cell types, and in agreement with the behavioral results, levels were higher for the differentiated C6-THA cells than for the undifferentiated cells. These results indicate that the GFAP promoter is sufficiently active to enable production of therapeutic levels of dopamine from a GFAP-TH transgene, and suggest the use of astrocytes for gene therapy for Parkinson's disease. They also show that beneficial modifications of cells produced by treatment while in culture may be maintained following implantation.

Animals↗