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Biomedical subjects

C Baamonde

Publications and source records attributed to C Baamonde.

At least 19 recordsLinked to original sources
PubMed2006

Brain G protein-dependent signaling pathways in Down syndrome and Alzheimer's disease.

Premature aging and neuropathological features of Alzheimer's disease (AD) are commonly observed in Down syndrome (DS). Based on previous findings in a DS mouse model, the function of signaling pathways associated with adenylyl cyclase (AC) and phospholipase C (PLC) was assessed in cerebral cortex and cerebellum of age-matched adults with DS, AD, and controls. Basal production of cAMP was reduced in DS but not in AD cortex, and in both, DS and AD cerebellum. Responses to GTPgammaS, noradrenaline, SKF 38393 and forskolin were more depressed in DS than in AD cortex and cerebellum. Although no differences in PLC activity among control, DS and AD cortex were observed under basal and GTPgammaS- or Ca-stimulated conditions, the response of DS cortex to serotonergic and cholinergic stimulation was depressed, and that of AD was only impaired at cholinergic stimulation. No differences were documented in cerebellum. Our results demonstrate that PLC and AC were severely disturbed in the aged DS and AD brains, but the alterations in DS were more severe, and differed to some extent from those observed in AD.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2006

Ischemic preconditioning and kidney transplantation: in vivo nitric oxide monitoring in a rat ischemia-reperfusion experimental model.

Direct nitric oxide measurement in live tissue would help us to understand its role in ischemia-reperfusion injury and its relationship to ischemic preconditioning (IP). We constructed four experimental groups of ischemia-reperfusion in the rat kidney: G1 were controls; G2, 1 hour of renal ischemia; G3 and G4: one or two 15/10 minute cycles, respectively, of IP prior to 1 hour of ischemia. Real-time in vivo nitric oxide measurements were compared with functional parameters of kidney damage at 24 hours. The peaks of nitric oxide production in the IP periods increased less in the rising curve of nitric oxide production during the 1 hour ischemia time. No improvement in the IP groups was observed based on serum creatinine levels at 24 hours.

Animals↗
PubMed2005

Long-term results of lung transplantation for emphysema.

INTRODUCTION: We sought to assess the differences between lung transplantation (LT) to treat emphysema, versus other pulmonary diseases. METHODS: This retrospective review of lung transplantations (LTs) performed from October 1993 to September 2003, included donor and recipient demographic data, pulmonary function, oxygenation, postoperative complications, incidence of rejection and pneumonia, and survival. RESULTS: Of 159 LTs performed the 39 transplanted to treat emphysema (24.4%), were in 33 men and 6 women of age 50.9 +/- 8.7 years (men, 25 to 65 years). There were differences between the emphysema vs other groups in terms of age (P < .001), gender (P = .001), need for bypass (P = .004), and immediate posttransplantation oxygenation index (P = .001). Perioperative mortality tended to be lower among patients with emphysema (2.7% vs 10.8%; P = .131). The incidences of complications and acute rejections was similar. Forced vital capacity, forced expiratory volume in 1 second, arterial oxygen tension, and arterial carbon dioxide tension improved significantly post-Tx. Actuarial survivals were 82%, 68%, and 63%, respectively, at 1, 3, and 7 years posttransplantation for emphysema patients vs 60%, 53%, and 42%, respectively, at 1, 3, and 7 years posttransplantation for non-emphysema patients (P = .049). CONCLUSION: Lung transplantation in patients with emphysema offers good long-term survival, with significant improvement in functional status and low morbidity. The older age of emphysema patients was not associated with a higher incidence of postoperative complications.

Adult↗
PubMed2005

Pediatric lung transplantation.

INTRODUCTION: Pediatric lung transplantation (LT) was started in Spain in 1996 at our institution. We compare the results of pediatric LT with those in adult patients. METHODS: A retrospective review of LT patients from 1993 to 2003 included demographic donor and recipient data, pulmonary function, gas exchange parameters, complications, episodes of rejection and pneumonia, as well as survival. Patients were divided into 2 groups: pediatric (<16 years) and adult (>16 years) LT patients. RESULTS: Of 165 LTs performed, 23 recipients were pediatric patients (10 boys, 13 girls; mean age, 11.9 +/- 2.9 years [range, 5-16 years]). The indications were cystic fibrosis (n = 21), pulmonary fibrosis (n = 1), and Kartagener syndrome (n = 1). The actuarial survival rate was 73%, 67%, and 62% at 1, 3, and 8 years post-LT in children, versus 67%, 56%, and 41% at 1, 3, and 8 years post-LT in adult patients (P = NS). Of the pediatric patients, 35% required mechanical ventilation preoperatively (P < .001). Pediatric patients showed a higher incidence of pneumonia (P < .01) and acute rejection episodes (P = .02) during the first month post-LT, and longer stays in the intensive care unit (P = .02). Pediatric patients displayed more immunosuppression-related adverse effects: diabetes (P = .04), neuropathy (P < .01), and hirsutism (P < .001). In children, arterial oxygen tension improved, from 51 mm Hg pre-LT to 93 mm Hg at 5 years post-LT. Forced expiratory volume in 1 second improved from 28% pre-LT to 84% at 5 years post-LT. CONCLUSION: In children, LT is a high-risk procedure because of the critical status of these patients. However, the results of pediatric LT are similar to those in adults, but with better long-term survival.

Adolescent↗
PubMed2005

Analysis of lung transplant recipients surviving beyond 5 years.

INTRODUCTION: We started lung transplantation (LT) in October 1993 and review the status of recipients who have survived beyond 5 years. METHODS: A retrospective review of patients undergoing LT from October 1993 to October 1998 included pulmonary function data, incidence of bronchiolitis obliterans syndrome (BOS), functional status, and survival. RESULTS: Of 73 transplantations 41 (56%) patients have survived beyond 5 years (study group), including 23 men and 18 women of age 33.2 +/- 15.6 years. Indications for LT were as follows: cystic fibrosis (n = 16), emphysema (n = 13), pulmonary fibrosis (n = 8), and other (n = 4). Actuarial survival at 5, 7, and 9 years was 56%, 53%, and 43%, respectively. Freedom from BOS was 63%, 56%, and 50% at 5, 7, and 9 years, respectively. The median percent predicted FEV1 was 67%, 56%, and 56%, respectively. Also, 79% of recipients had no limitations in their daily activities; 65% were active and working. Only 5% of patients showed some degree of limitation at 5 years posttransplantation. When survivors beyond 5 years were compared with nonsurvivors beyond 5 years, differences were observed: nonsurvivors more frequently required bypass (P = .01), experienced longer postoperative intubation times (P = .01), and exhibited lower PaO2 at 12 months posttransplantation (P < .01). CONCLUSION: Our data show good survival rates among patients surviving beyond 5 years after LT, with a moderate incidence of BOS at 9 years posttransplantation. Despite the incidence of BOS, these patients have good pulmonary function and activity status.

Actuarial Analysis↗
PubMed2005

Pulmonary tailoring and lobar transplantation to overcome size disparities in lung transplantation.

Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplant teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, surgical procedures such as pulmonary tailoring and lobar transplantation have been advocated. We review our experience in 13 patients undergoing volume reduction of the lung graft at the time of transplantation, either by nonanatomical lung volume reduction or by lobar transplantation. There were no significant differences between lung-downsized patients and standard lung transplantation patients in terms of donor characteristics, surgical and postoperative complications, functional outcome, and survival. We conclude that downsizing the lung graft either by nonanatomical resection or lobar transplantation is safe and reliable to overcome size disparities between donor and recipients, with no additional morbidity and with similar early and midterm outcomes to those in standard lung transplants.

ABO Blood-Group System↗
PubMed2003

Lung transplants with tacrolimus and mycophenolate mofetil: a review.

Traditionally, immunosuppressive maintenance therapy in solid organ transplantation has consisted of cyclosporine (CsA), azathioprine, and prednisone. However, lung transplant recipients are far more frequently affected by acute rejection, especially during the first 6 months after the transplantation, than patients with other transplanted organs. Further, they display a greater risk for chronic transplant dysfunction and ultimate graft loss. Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and mortality among long-term survivors after lung transplantation. Acute pulmonary allograft rejection has been identified as the major risk factor for the development of BOS. Based on favourable results in kidney, liver, and heart transplantation, tacrolimus and mycophenolate mofetil have been used as primary prophylaxis and as rescue therapy for recurrent or persistent acute rejection and BOS. A secondary indication is CsA toxicity. This review focuses on reported results of the combination of tacrolimus and mycophenolate mofetil in lung transplantation. These new immunosuppressive drugs have markedly improved the efficacy profiles without additional detrimental toxicities, and appear to be a safe alternative to CsA and azathioprine in patients following lung transplantation. However, at present, BOS is not influenced by these new drugs. The optimal long-term immunosuppressive regimen remains to be established.

Clinical Trials as Topic↗
PubMed2002

Postnatal handling induces long-term modifications in central beta-noradrenergic signalling in rats.

Neonatal handling has been shown to induce a short-term reduction in the binding properties of beta-adrenoceptors and in their primary biochemical responses in the young rat brain, which may account for the reduced responsiveness to stress observed in the handled rats. We have studied the persistence and duration of these changes in cerebral cortex, cerebellum and hippocampus at successive stages of life in neonatally handled rats. Binding properties of the beta-adrenoceptors in handled animals were essentially similar to those of the control rats from 3 to 24 months of age. However, handling disturbed the efficacy of the beta-adrenoceptor intracellular signalling since the isoprenaline-induced accumulation of cyclic AMP was reduced in cerebral cortex at 1, 12 and 24 months; in cerebellum at 12 and 18 months; and in hippocampus at 3 and 12 months. This effect might be partially dependent on a regulatory action of handling on the adenylyl cyclase enzyme itself since both basal and forskolin-induced accumulation of cyclic AMP were persistently reduced. Therefore, postnatal handling can be considered as an effective intervention that modifies sensitivity to various hormonal and neurochemical signals; these changes may be involved over a long period of time in protection against an excessive response to stress. These results suggest that the long-lasting adaptation of the adenylyl cyclase transduction system, which affects the primary biochemical response of the beta-adrenoceptor, may participate in the effects of this manipulation.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Reduced phospholipase C-beta activity and isoform expression in the cerebellum of TS65Dn mouse: a model of Down syndrome.

Agonist- and guanine-nucleotide-stimulated phospholipase C-beta (PLC) activity was characterized in crude plasma membrane preparations from cerebral cortex, hippocampus and cerebellum of Ts65Dn mice, a model for Down syndrome, and their control littermates. The levels of expression of PLC-beta((1-4)) isoforms and G-protein alpha(q/11) subunits were also quantified by Western blot analysis to establish their contribution to the patterns of PLC functioning. PLC activity regulated by G-proteins and muscarinic and 5-HT(2) receptors presented a regional distribution in both control and Ts65Dn mice. In both groups of mice, the intensity of PLC responses to maximal activation by calcium followed the sequence cerebellum > cortex > hippocampus. Both basal and maximal PLC activities, however, were significantly lower in cerebellar membranes of Ts65Dn than in control mice. This difference was mostly revealed in crude plasma membranes prepared from cerebellum at the level of G-protein-dependent-PLC activity because the concentration-response curve to GTPgammaS showed a reduction of the maximal effect in Ts65Dn mice, with no change in sensitivity (EC(50)). Western blot analysis showed a heterogeneous distribution of PLC-beta((1-4)) isoforms in both groups of mice. The levels of PLC-beta4 isoform, however, were significantly lower in the cerebellum of Ts65Dn than in control mice. We conclude that the cerebellum of Ts65Dn mice has severe deficiencies in PLC activity stimulated by guanine nucleotides, which are specifically related to a lower level of expression of the PLC-beta4 isoform, a fact that may account for the neurological phenotype observed in this murine model of Down syndrome.

Animals↗
PubMed2001

Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome.

Down's syndrome (DS) is a major cause of mental retardation, hypotonia and delayed development. Murine models of DS carrying large murine or human genomic fragments show motor alterations and memory deficits. The specific genes responsible for these phenotypic alterations have not yet been defined. DYRK1A, the human homolog of the Drosophila minibrain gene, maps to the DS critical region of human chromosome 21 and is overexpressed in DS fetal brain. DYRK1A encodes a serine-threonine kinase, probably involved in neuroblast proliferation. Mutant Drosophila minibrain flies have a reduction in both optic lobes and central brain, showing learning deficits and hypoactivity. We have generated transgenic mice (TgDyrk1A) overexpressing the full-length cDNA of Dyrk1A. TgDyrk1A mice exhibit delayed cranio-caudal maturation with functional consequences in neuromotor development. TgDyrk1A mice also show altered motor skill acquisition and hyperactivity, which is maintained to adulthood. In the Morris water maze, TgDyrk1A mice show a significant impairment in spatial learning and cognitive flexibility, indicative of hippocampal and prefrontal cortex dysfunction. In the more complex repeated reversal learning paradigm, this defect turned out to be specifically related to reference memory, whereas working memory was almost unimpaired. These alterations are comparable with those found in the partial trisomy chromosome 16 murine models of DS and suggest a causative role of DYRK1A in mental retardation and in motor anomalies of DS.

Animals↗
PubMed2001

Prediction of early bronchopleural fistula after pneumonectomy: a multivariate analysis.

BACKGROUND: The aim of this study was to determine independent risk factors for early bronchopleural fistula (BPF) after pneumonectomy and to assess the efficacy of bronchial coverage in preventing this complication. METHODS: We reviewed 242 consecutive patients undergoing pneumonectomy for lung cancer. The bronchial stump was covered with autologous tissue in 178 patients (74%). Perioperative data were recorded to identify risk factors of BPF by univariate and multivariate analyses. RESULTS: Overall morbidity and mortality rates were 59% and 5.4%, respectively. The incidence of BPF was 5.4%. By univariate analysis, patients with chronic obstructive pulmonary disease (COPD; p = 0.017), hyperglycemia (p = 0.003), hypoalbuminemia (p = 0.017), previous steroid therapy (p < 0.001), poor predicted postpneumonectomy forced expiratory volume in 1 second (FEV1; p = 0.012), long bronchial stumps (p < 0.001), and mechanical ventilation (p = 0.015), were related with higher risk of BPF. In the multiple logistic regression model, the independent risk factors of BPF were the bronchial stump coverage and length, side of pneumonectomy, predicted postpneumonectomy FEV1, COPD, and mechanical ventilation. CONCLUSIONS: Bronchial stump coverage is highly recommended in all cases to minimize the risks of BPF. A shorter length of the bronchial stump and early extubation may prevent the development of BPF. Careful attention must be paid to those patients with COPD and poor predicted postpneumonectomy FEV1.

Adult↗
PubMed2001

Airway complications after lung transplantation: a review of 151 anastomoses.

OBJECTIVE: To analyze the incidence, treatment and follow up of airway complications after lung transplantation. METHODS: From October 1993 to April 2000, 104 lung transplants were performed in 101 patients. One hundred and fifty one bronchial anastomoses at risk were included in the study (29 single lung and 61 sequential double lung). Donor lungs were flushed both antegradely and retrogradely with Eurocollins. In the recipients, either a single or a sequential bilateral lung transplantation was performed when indicated. The bronchial anastomosis was telescoped and covered with peribronchial tissue in all cases. Postoperative fiberoptic bronchoscopic examinations were dictated by clinical grounds. Recipient variables were recorded and analyzed to assess possible differences between both complicated and non-complicated groups. RESULTS: Eight bronchial anastomotic complications (5.3%) occurred in six patients (6.8%). All complicated cases developed in sequential bilateral lung recipients (P=0.08): stenosis (n=5), granulation tissue (n=2), and bronchial dehiscence (n=1). Treatment consisted of lobectomy and subsequent completion pneumonectomy in one patient, rigid bronchoscopy dilation in two, balloon bronchodilation in two, laser debridement and stenting in one, and conservative therapy in two cases. One patient with severe sepsis and bronchial dehiscence died on day +30. The rest of the patients remain well so far. Airway complications were related to longer intubation periods (P<0.01). Other perioperative donor and recipient factors including the incidence of infections and acute rejection episodes, and actuarial survival, did not differ between groups. CONCLUSION: In our experience, the incidence of airway complications after lung transplantation is 5.3%. The careful surgical technique and organ preservation, the close surveillance of rejection and infection, and early postoperative extubation might play a role in reducing this incidence. Either surgical therapy or bronchoscopic dilation and stenting methods may contribute to resolve these complications.

Adolescent↗
PubMed1999

A murine model for Down syndrome shows reduced responsiveness to pain.

Ts65Dn mice have an extra chromosome that contains a segment of chromosome 16 homologous to the Down syndrome 'critical region' of human chromosome 21. Since pain transmission and expression may be limited in people with mental disabilities, including Down syndrome, responsiveness to nociception in Ts65Dn mice was compared with that in their control litter-mates. In the formalin test, a model of tonic pain, Ts65Dn mice showed depressed sensitivity to nociception during the early and late phases. In the tail-flick test, they showed longer latencies than controls, but no differences among groups were observed in morphine responses. In the hot-plate test, no changes were observed in escape latencies during the first exposure, but Ts65Dn mice showed smaller tendency to lick. The results indicate that trisomic mice present an overall depressed responsiveness to nociceptive stimulation.

Animals↗
PubMed1999

Short-term effects of postnatal manipulation on central beta-adrenoceptor transmission.

Neonatal handling is known to induce long-lasting changes in behavioral and neuroendocrine responses to stress. Since the central noradrenergic system participates in the adaptive responses to stressful conditions we have analyzed the effects of postnatal handling on beta-adrenoceptor binding sites and isoprenaline- and forskolin-stimulated cyclic AMP accumulation in cerebral cortex, hippocampus and cerebellum of rats at 1 and 3 months of age. Handled animals showed reduced emotional reactivity and lower ACTH and corticosterone secretion after stress. Binding studies using [(3) H]CGP12-177 revealed increased beta-adrenoceptor binding sites in handled rats in cerebellum and cerebral cortex with no changes in hippocampus, and decreased affinity in all cerebral regions. Handling reduced basal levels of cyclic AMP in hippocampus and cerebellum but not in cerebral cortex. The concentration-response curves of cyclic AMP to isoprenaline were displaced to the right in cerebellum of handled rats without differences in Emax; however, Emax was significantly reduced in cerebral cortex and hippocampus. Direct stimulation of the catalytic subunit of adenylyl cyclase by forskolin reduced the efficiency in hippocampus and cerebellum, but not in cerebral cortex of handled animals. It is concluded that neonatal handling reduces the binding properties of beta-adrenoceptor and its primary biochemical responses in the young rat brain, which may account for the reduced responsiveness to stress attained in the handled rats, and may explain the persistence of the effect. The present study emphasizes the role of the central noradrenergic system in modulating the behavioral and neurendocrine responses to neonatal handling.

Adenylyl Cyclases↗
PubMed1998

Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome.

Ts65Dn (TS), control littermates (CO) and Swiss (SW) male mice were tested in the elevated plus-maze and in the Morris water maze (MWM) for memory evaluation. In the plus-maze, each mouse was placed at the end of an open arm and initial freezing and the time to enter into an enclosed arm (transfer latency) were measured. SW mice decreased both measures over repeated trials, whereas no decrease of freezing was observed in CO mice, thus suggesting increased emotionality in this group. Compared to CO mice, TS mice showed less initial freezing, shorter transfer latencies, and spent less time in enclosed arms, suggesting a reduced ability to habituate or to inhibit behaviour. Animals were also submitted to a learning-set paradigm consisting of reaching a new platform position each day in the MWM. Two training phases (separated by a resting period of 6 weeks), each including eight acquisition and four cued sessions, were performed (each session consisting of four pairs of trials). CO and SW mice already reached an asymptotic performance by the second day of the first phase whereas TS mice did not achieve that level until the second training phase. The progression over trials indicated that CO and SW animals learned the new platform position between trials 1 and 2 of each session, whereas TS animals failed to do it and had more difficulties to find the platform when it was placed in the centre of the pool as compared to the other positions (SW, NE, E). The results suggest that TS mice show working memory impairments in addition to long-term memory deficits, although extensive training appeared to facilitate TS mice to achieve a level of performance similar to their control littermates. This represents another aspect of the cognitive deficits shown by TS mice: a mouse model of the human Down syndrome.

Animals↗