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Biomedical subjects

C Garcia

Publications and source records attributed to C Garcia.

At least 37 records · Page 2Linked to original sources
PubMed2003

Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant.

Antidepressants and physical exercise have been shown to increase the transcription of hippocampal brain-derived neurotrophic factor (BDNF). Much evidence regarding the initial actions of antidepressant medications as well as exercise leads to the hypothesis that noradrenergic (NE) and/or serotonergic (5-HT) activation is a key element in the BDNF transcriptional elevation common to both interventions. Currently, we used short-term beta-adrenergic, 5-HT(1A), or 5-HT(2A/C) receptor blockade to characterize the influence of NE and 5-HT systems on BDNF transcription during physical exercise and antidepressant treatment. In situ hybridization revealed that beta-adrenergic blockade significantly blunted the BDNF mRNA elevations due to exercise, and also inhibited the modest elevations in the CA3 and dentate gyrus following short-term treatment with tranylcypromine. In contrast, 5-HT(2A/C) blockade only minimally altered exercise-induced BDNF mRNA levels, but inhibited up-regulation of BDNF transcription via tranylcypromine. Finally, 5-HT(1A) blockade did not inhibit exercise-induced BDNF mRNA elevations, but significantly enhanced levels above those achieved with exercise alone in the CA4. These results suggest that NE activation via beta-adrenergic receptors may be essential for both exercise and antidepressant-induced BDNF regulation. 5-HT(1A) and 5-HT(2A/C) activation, on the other hand, appear to be most important for antidepressant-induced BDNF regulation, but may also participate significantly in exercise-induced regulation in the CA4.

Adrenergic Antagonists↗
PubMed2003

The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity.

Previous studies have shown that hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels are significantly increased in rats allowed free access to exercise wheels and/or administered antidepressant medications. Enhancement of BDNF may be crucial for the clinical effect of antidepressant interventions. Since increased function of the noradrenergic and/or serotonergic systems is thought to be an important initial mechanism of antidepressant medications, we sought to test the hypothesis that noradrenergic or serotonergic function is essential for the increased BDNF transcription occurring with exercise. In addition, individual transcript variants of BDNF were examined, as evidence exists they are differentially regulated by discrete interventions, and are expressed in distinct sub-regions of the hippocampus. The neurotransmitter system-specific neurotoxins p-chloroamphetamine (serotonergic) and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (noradrenergic) were administered to rats prior to commencing voluntary wheel-running activity. In situ hybridization experiments revealed an absence of exercise-induced full-length BDNF mRNA elevations in the hippocampi of noradrenergic-lesioned rats. In addition, the striking elevation of the exon I transcript in the dentate gyrus was removed with this noradrenergic lesion. In contrast, other transcript variants (exons II and III) were elevated in several hippocampal regions as a result of this lesion. In serotonin-lesioned rats, the significant increases in full-length BDNF, exon I and exon II mRNA levels were sustained without alteration (with the exception of exon IV in the cornus ammonis subregion 4, CA4). Overall, these results indicate that an intact noradrenergic system may be crucial for the observed ability of exercise to enhance full-length and exon I hippocampal BDNF mRNA expression. In addition, these results suggest that the promoter linked to exon I may provide a major regulatory point for BDNF mRNA expression in the dentate gyrus. Elevations of other exons, such as II and III, may require the activation of separate neurotransmitter systems and intracellular pathways.

Alternative Splicing↗
PubMed2003

Treatment of lentigo maligna with topical imiquimod.

A published case report and anecdotal experience suggested that topical imiquimod is an effective treatment for stage 0 melanoma (lentigo maligna). To gauge the efficacy of this therapy, we undertook a trial of topical imiquimod in 30 subjects with histologically confirmed lentigo maligna. Thirty subjects with lentigo maligna were recruited for an open-labelled efficacy trial with daily topical application of imiquimod 5% cream for 3 months. Study subjects were enrolled from the Dermatology service of the University of Oklahoma, the Oklahoma City Veteran's Administration Hospital Dermatology service and from referrals for the study from other practitioners. In order to determine an initial response rate, a four-quadrant biopsy was carried out on all patients 1 month after cessation of treatment, targeting the most clinically and dermatoscopically suspicious areas. Of 28 evaluable subjects who have completed the 3-month treatment phase, 26 (93%) were complete responders and two were treatment failures at the time of the 4-quadrant biopsy. Over 80% of the 28 subjects that completed treatment have been followed for more than 1 year with no relapses. The results of this study demonstrate that topical imiquimod produces a high complete response rate in lentigo maligna when applied daily for 3 months.

Adjuvants, Immunologic↗
PubMed2003

Anaesthetics and cardiac preconditioning. Part II. Clinical implications.

There is compelling evidence that preconditioning occurs in humans. Experimental studies with potential clinical implications as well as clinical studies evaluating ischaemic, pharmacological and anaesthetic cardiac preconditioning in the perioperative setting are reviewed. These studies reveal promising results. However, there are conflicting reports on the efficacy of preconditioning in the diseased and aged myocardium. In addition, many anaesthetics and a significant number of perioperatively administered drugs affect the activity of cardiac sarcolemmal and mitochondrial K(ATP) channels, the end-effectors of cardiac preconditioning, and thereby markedly modulate preconditioning effects in myocardial tissue. Although these modulatory effects on K(ATP) channels have been investigated almost exclusively in laboratory investigations, they may have potential implications in clinical medicine. Important questions regarding the clinical utility and applicability of perioperative cardiac preconditioning remain unresolved and need more experimental work and randomized controlled clinical trials.

Adaptation, Physiological↗
PubMed2003

Chromosome homology between chicken (Gallus gallus domesticus) and the red-legged partridge (Alectoris rufa); evidence of the occurrence of a neocentromere during evolution.

Chromosome-specific paints from macrochromosomes 1-9 and Z of the chicken were hybridised to metaphases of the red-legged partridge and revealed no inter-chromosomal rearrangements. The results from chromosome painting are similar to previous studies on the Japanese quail but different from findings in guinea fowl and several species of pheasant. The difference in centromere position in chicken and partridge chromosome 4, previously assumed to be the result of an inversion, was confirmed. However, FISH mapping of BAC clones from chicken chromosome 4 revealed that the order of loci was the same in both species, indicating the occurrence of a neocentromere during divergence.

Animals↗
PubMed2003

Evaluation of bronchoalveolar cells in pulmonary paracoccidioidomycosis.

To investigate the local immune response, the cellular infiltrate and cytokine levels were analysed in bronchoalveolar lavage (BAL) from patients with pulmonary paracoccidioidomycosis. The group consisted of 19 patients aged 34-65 yrs. The diagnosis was confirmed by demonstration of the fungus in the sputum or BAL fluid and by serological tests. Cytospin preparations showed an increased number of lymphocytes and neutrophils in BAL. A higher number of CD8+ lymphocytes were observed in BAL compared with peripheral blood. Alveolar macrophages (AM) expressed approximately three-fold more major histocompatibility class II, intercellular adhesion molecule-1 and B7-2 molecules on their surfaces than their circulating counterparts, indicating that they had differentiated into activated macrophages inside the lungs. Cultured AM produced higher levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-1alpha than peripheral blood monocytes. BAL fluid contained low but detectable amounts of IL-6, TNF-alpha and MIP-1alpha, and specific antibodies to Paracoccidioides brasiliensis, mainly of the immunoglobulin G2 isotype. As macrophage inflammatory protein-1alpha was shown to selectively attract CD8+ T-cells and this population was elevated in bronchoalveolar lavage, the data suggest that, besides macrophages, CD8+ T-cells may have an important role in the pathogenesis of pulmonary paracoccidioidomycosis.

Adult↗
PubMed2002

Effectiveness of municipal waste compost and its humic fraction in suppressing Pythium ultimum.

The effect of addition of a municipal solid waste (MSW) compost and its water-soluble and humic fraction to suppress the effect of Pythium ultimum on pea plants was studied and compared with that of a chemical pesticide (metalaxyl). The biotic and abiotic characteristics of compost involved in the biocontrol effects of these materials were also evaluated. The addition into soil of whole composts and their humic fractions reduced the effect of the pathogen on pea plants, significantly reducing the number of root lesions and Pythium populations and avoiding reductions of plant growth. The greatest pathogen suppression was achieved with the chemical pesticide. However, it also caused a significant decrease in the number of nontarget bacteria and fungi and on beneficial soil microorganisms such as Trichoderma and Pseudomonas. Addition of organic amendments increased population size of nontarget and specific biocontrol microorganisms. The humic fraction showed similar results to compost. All this suggests that metalaxyl has a nonspecific effect, producing adverse effects on aspects of soil quality. This was avoided if the chemical pesticide was reduced and replaced by organic amendments such as an MSW compost or its humic fraction.

Agriculture↗
PubMed2001

Ethyl 6-amino-2-methoxypyridine-3-carboxylate, interplay of molecular and supramolecular structure.

The title compound, C(9)H(12)N(2)O(3), crystallizes with two molecules in the asymmetric unit. There is extensive hydrogen bonding which results in the formation of a two-dimensional corrugated sheet. This supramolecular structure is determined by the formation of hydrogen-bonded chains resulting from the presence of a 6-amino group and an ethoxycarbonyl group as substituents on a pyridine ring in relative para positions which constitute a pi-electron 'push-pull' system.

Journal Article↗
PubMed2001

Ketoconazole-induced conformational changes in the active site of cytochrome P450eryF.

The azole-based P450 inhibitor ketoconazole is used to treat fungal infections and functions by blocking ergosterol biosynthesis in yeast. Ketoconazole binds to mammalian P450 enzymes and this can result in drug-drug interactions and lead to liver damage. To identify protein-drug interactions that contribute to binding specificity and affinity, we determined the crystal structure of ketoconazole complexed with P450eryF. In the P450eryF/ketoconazole structure, the azole moiety and nearby rings of ketoconzole are positioned in the active site similar to the substrate, 6-deoxyerythronolide B, with the azole nitrogen atom coordinated to the heme iron atom. The remainder of the ketoconazole molecule extends into the active-site pocket, which is occupied by water in the substrate complex. Binding of ketoconazole led to unexpected conformational changes in the I-helix. The I-helix cleft near the active site has collapsed with a helical pitch of 5.4 A compared to 6.6 A in the substrate complex. P450eryF/ketoconazole crystals soaked in 6-deoxyerythronolide B to exchange ligands exhibit a structure identical with that of the original P450eryF/substrate complex, with the I-helix cleft restored to a pitch of 6.6 A. These findings indicate that the I-helix region of P450eryF is flexible and can adopt multiple conformations. An improved understanding of the flexibility of the active-site region of cytochrome P450 enzymes is important to gain insight into determinants of ligand binding/specificity as well as to evaluate models for catalytic mechanism based on static crystal structures.

Animals↗
PubMed2001

CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans.

Somatically mutated IgM(+)-only and IgM(+)IgD(+)CD27(+) B lymphocytes comprise approximately 25% of the human peripheral B cell pool. These cells phenotypically resemble class-switched B cells and have therefore been classified as postgerminal center memory B cells. X-linked hyper IgM patients have a genetic defect characterized by a mutation of the CD40L gene. These patients, who do not express a functional CD40 ligand, cannot switch Ig isotypes and do not form germinal centers and memory B cells. We report here that an IgM(+)IgD(+)CD27(+) B cell subset with somatically mutated Ig receptors is generated in these patients, implying that these cells expand and diversify their Ig receptors in the absence of classical cognate T-B collaboration. The presence of this sole subset in the absence of IgM(+)-only and switched CD27(+) memory B cells suggests that it belongs to a separate diversification pathway.

Adolescent↗
PubMed2001

Basiliximab induction improves the outcome of renal transplants in children and adolescents.

Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with <or=3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels.

Adolescent↗
PubMed2001

Reduction of donor exposures in premature infants by the use of designated adenine-saline preserved split red blood cell packs.

OBJECTIVE: Critically ill neonates frequently require multiple small volume red blood cell (RBC) transfusions. RBC units assigned to individual infants, used sequentially in small aliquots until the original expiration date, can substantially reduce donor exposures. In 1993, adenine-saline solution (AS-3) was introduced by the Canadian Red Cross as the red cell storage medium to replace citrate-phosphate-dextrose-adenine anticoagulant-preservative solution (CPDA-1). We surveyed the safety and efficacy of using AS-3 split packs, stored up to 35 days, for premature infants. STUDY DESIGN: Units of packed cells were aseptically welded to three satellite bags using a sterile connecting device. When blood was requested for a small volume transfusion, the first satellite bag was used and the others were set aside for the same baby, for use up until their expiration date of 35 days. RESULTS: Over a 1-year period, 56 infants received a total of 263 AS-3 transfusions from 97 donors, with a mean of 4.7 transfusions and 1.7 donor exposures per infant. Following a 7-ml/kg RBC transfusion, mean rise in hematocrit (hct) was 0.04, regardless of the age of the unit, mean change in serum potassium was -0.16 mmol/l and mean change in total bilirubin was +1.86 micromol/l. The posttransfusion hct was not reduced with the use of the older red cell packs. CONCLUSION: Designated AS-3-preserved split RBC packs effectively limit donor exposures, can safely be used for neonatal small volume transfusions, and give a constant transfusion effect after up to 35 days of storage.

Adenine↗
PubMed2001

Orthotopic liver transplantation for alcoholic liver disease: a retrospective analysis of survival, recidivism, and risk factors predisposing to recidivism.

The aim of this study performed at the Liver Unit at the Queen Elizabeth Hospital, Birmingham, UK, is to assess posttransplantation alcohol consumption and identify risk factors associated with recidivism. This retrospective case-control study used a self-report questionnaire to assess pretransplantation and posttransplantation drinking, and a retrospective cohort study used patient notes to analyze risk factors for recidivism. Of 64 patients who underwent transplantation for alcoholic liver disease (ALD) between May 1996 and November 1999, a total of 49 surviving patients (40 men, 9 women) were available for study. The comparison group consisted of 49 patients matched for age, sex, and date of transplantation who underwent transplantation for non-alcohol-induced chronic liver disease. Two-year patient survival rates were 82% in both study groups. The questionnaire response rate was 69.3% and 75.5% in patients with and without ALD, respectively. Data on recidivism (defined as any alcohol consumption after transplantation) were available in 46 of the 49 patients with ALD. Of these, 45.6% were drinking; 21.7% reported only occasionally drinking; 17.3%, moderate drinking; and 6.5%, heavy drinking. Information on alcohol consumption was available from 41 of the 49 controls. Of these, 52.5% consumed alcohol; 22.0% reported drinking only on special occasions; 24.4%, moderate drinking; and 4.9%, a return to heavy drinking. However, these differences were not statistically significant, and log-rank analysis found no significant difference in time to resumption of drinking. In the ALD cohort, no significant risk factors were identified to predict recidivism. No pretransplantation risk factors (including period of abstinence before transplantation) correlated with recidivism. Survival after transplantation for ALD is similar to that in other forms of chronic liver disease. Recidivism rates for patients with ALD are high, but patients with ALD do not drink more than their control counterparts posttransplantation. In most instances, alcohol consumption posttransplantation is minimal to moderate (<20 units/wk) and seems to be controlled.

Adult↗
PubMed2001

Glucagon-like peptide-1(7-36) amide stimulates surfactant secretion in human type II pneumocytes.

To determine the influence of glucagon-like peptides on the secretion of human pulmonary surfactant, we used human type II pneumocytes. In these cells, GLP-1(7-36) amide and exendin-4 stimulated phosphatidylcholine secretion (PC) and cAMP formation in a concentration-dependent manner; these effects were reversed by exendin(9-39). No changes were observed with other related peptides. The mechanism by which GLP-1(7-36) amide exerts its stimulatory effect was investigated with various agents that are well known to be stimulators or inhibitors of PC secretion. Thus, 8-bromo-cAMP increased and both Rp-cAMPS and H-89, the latter an inhibitor of protein kinase A (PKA), reduced pulmonary surfactant secretion in type II pneumocytes. Also, GLP-1(7-36) amide and TPA exerted additive effects in stimulating PC secretion, and Calph C, a potent inhibitor of protein kinase C (PKC), blocked most of the effect of GLP-1(7-36) amide. By contrast, both the calcium ionophore A23187 and GLP-1(7-36) amide had additive effects in increasing PC secretion, and the specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase (Ca-CM-PK), KN-62, inhibited the effect of A23187 but did not alter the stimulatory action of GLP-1(7-36) amide. Our findings suggest that both PKA and PKC are involved in the stimulatory effects of GLP-1(7-36) amide on PC secretion, whereas this peptide has no effect on PC secretion through a Ca-CM-PK mechanism.

Adult↗