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Biomedical subjects

Javier García

Publications and source records attributed to Javier García.

At least 37 records · Page 2Linked to original sources
PubMed2005

Tumor necrosis factor-alpha gene expression in diabetic nephropathy: relationship with urinary albumin excretion and effect of angiotensin-converting enzyme inhibition.

BACKGROUND: The pathogenic mechanisms and molecular events involved in the development and progression of diabetic nephropathy (DN) are not completely known. Recent data indicate that diabetes includes an inflammatory component that is related to diabetic complications. Tumor necrosis factor (TNF)-alpha, a cytokine with mainly proinflammatory activity, may be synthesized by renal cells. Our objective was to analyze intrarenal TNF-alpha gene expression and its relationship with urinary albumin excretion (UAE). We also investigated the effect of inhibition of angiotensin-converting enzyme on TNF-alpha expression and UAE. METHODS: Streptozotocin-induced diabetic rats received either no treatment or an angiotensin-converting enzyme inhibitor (enalapril). After eight weeks, renal expression of TNF-alpha was evaluated by real-time polymerase chain reaction. RESULTS: Renal cortical messenger RNA levels of TNF-alpha increased significantly and were twice as high in diabetic rats than in nondiabetic control rats. Enalapril administration nearly completely abolished the increase in TNF-alpha messenger RNA expression to the level observed in control rats. UAE was significantly correlated with urinary levels of TNF-alpha (r=0.68, P<0.05) and with renal TNF-alpha expression (r=0.51, P<0.05). CONCLUSION: DN was associated with increased renal expression of TNF-alpha and UAE. Enalapril administration prevented this enhanced expression of TNF-alpha and decreased urinary cytokine excretion and albuminuria. These data provide a novel insight into the pathogenic mechanisms of DN, and support the hypothesis that inflammatory mechanisms may play a significant role in the development and progression of renal injury secondary to diabetes mellitus.

Albuminuria↗
PubMed2004

Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions.

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologic substrate and a reduction in CAN. METHODS: We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups. RESULTS: The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05). CONCLUSIONS: Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome.

Adolescent↗
PubMed2004

Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition.

BACKGROUND: Endocardial mapping before sustained monomorphic ventricular tachycardia (SMVT) induction may reduce mapping time during tachycardia and facilitate the ablation of unmappable VT. METHODS AND RESULTS: Left ventricular electroanatomic voltage maps obtained during right ventricular apex pacing in 26 patients with chronic myocardial infarction referred for VT ablation were analyzed to identify conducting channels (CCs) inside the scar tissue. A CC was defined by the presence of a corridor of consecutive electrograms differentiated by higher voltage amplitude than the surrounding area. The effect of different levels of voltage scar definition, from 0.5 to 0.1 mV, was analyzed. Twenty-three channels were identified in 20 patients. The majority of CCs were identified when the voltage scar definition was < or =0.2 mV. Electrograms with > or =2 components were recorded more frequently at the inner than at the entrance of CCs (100% versus 75%, P< or =0.01). The activation time of the latest component was longer at the inner than at the entrance of CCs (200+/-40 versus 164+/-53 ms, P< or =0.001). Pacing from these CCs gave rise to a long-stimulus QRS interval (110+/-49 ms). Radiofrequency lesion applied to CCs suppressed the inducibility in 88% of CC-related tachycardias. During a follow-up of 17+/-11 months, 23% of the patients experienced a VT recurrence. CONCLUSIONS: CCs represent areas of slow conduction that can be identified in 75% of patients with SMVT. A tiered decreasing-voltage definition of the scar is critical for CC identification.

Aged↗
PubMed2004

Regioselective enzymatic acylation of beta-L-2'-deoxynucleosides: application in resolution of beta-D/L-2'-deoxynucleosides.

[reaction: see text] A practical synthesis of beta-L-3'- and beta-L-5'-O-levulinyl-2'-deoxynucleosides has been described for the first time through enzymatic acylation and/or hydrolysis processes. It is noteworthy that the different behavior exhibited by Pseudomonas cepacia lipase in the acylation of D- and L-nucleosides allows the parallel kinetic resolution of D/L-nucleosides.

Acylation↗
PubMed2004

Sporozoite and liver stage antigen Plasmodium falciparum peptides bind specifically to human hepatocytes.

Sporozoite and Liver Stage Antigen (SALSA) sequence synthetic peptides were used in HepG2 cell binding assays to identify regions involved in parasite invasion. SALSA 20608 ( 21IWASEKKDEKEASEQGEESHY40) and 20611 ( 64KKDDGTDKVQEKVLEKSPKY83) peptides were determined as having high binding activity in HepG2 cell assays, some of them were located in immunogenic regions. Immune-fluorescence antibody test with 24276 (20608 peptide analogue, CGIWSSMKMDEKMAAMQGEESHCG) showed sporozoite and merozoite reactivity. This data suggests SALSA high activity binding peptides' (HABPs) possible role in hepatic cell invasion and merozoite invasion of erythrocytes.

Amino Acid Sequence↗
PubMed2004

Specific erythrocyte binding capacity and biological activity of Plasmodium falciparum-derived rhoptry-associated protein 1 peptides.

Rhoptry-associated protein 1 (RAP1) is a merozoite antigen within Plasmodium falciparum rhoptries as yet having no specific function described for it. Synthetic peptides spanning the RAP1 sequence were tested in erythrocyte binding assays to identify possible RAP1 functional regions. Five high activity binding peptides (HABPs) were identified; 26201, 26202, 26203 and 26204 spanned residues 461C-K540 within RAP1 Cys region, whilst 26188 (201T-Y220) was located in p67 amino terminal. The results showed that peptide binding was saturable, some HABPs inhibited in vitro merozoite invasion and specifically bound to a 72 kDa protein in red blood cell membrane. HABP possible function in merozoite invasion of erythrocytes is also discussed.

Amino Acid Sequence↗
PubMed2004

Recognition of polychromatic three-dimensional objects.

We propose to use optical multichannel correlation in various chromatic systems to obtain a setup for recognition of polychromatic three-dimensional (3-D) objects based on Fourier-transform profilometry. Because red-green-blue color components are not able to split the luminance information of objects in a defined component, when the 3-D objects are brighter than the reference objects the correlation result gives false alarms. We demonstrate that it is possible to use different color spaces that can split luminance from chromatic information to yield adequate recognition of polychromatic 3-D objects. We show experimental results that prove the utility of the proposed method.

Journal Article↗
PubMed2004

Plasmodium falciparum: red blood cell binding studies using peptides derived from rhoptry-associated protein 2 (RAP2).

Plasmodium falciparum rhoptry-associated proteins 1 (RAP1) and 2 (RAP2) are antigens presenting themselves as candidates for a subunit malaria vaccine. RAP2 protein, non-overlapping, consecutive peptides were synthesised and tested in red blood cell (RBC) binding assays to identify their receptor-ligand interaction in recognising RAP2 regions involved in the in vitro merozoite invasion process. Four high activity binding peptides (HABPs) were identified in the resulting 20 peptides. Peptides 26220 ((61)NHFSSADELIKYLEKTNINT(80)), 26225 ((161)IKKNPFLRVLNKASTTTHAT(180)) and 26229 ((241)RSVNNVISKNKTLGLRKRSS(260)) were located in the amino terminal and central part of the protein and HABP 26235 ((361)FLAEDFVELFDVTMDCYSRQ(380)) was located at the carboxy terminal. All these HABPs showed saturable binding and presented dissociation constants between 500 and 950 nM; the number of binding sites per RBC ranged from 48,000 to 160,000. High binding peptides' critical amino acids involved in RBC binding were determined by competition binding assays; their amino acids appear in bold in the sequences shown above. SDS-PAGE results showed that peptides 26220, 26225 and 26229 had at least two different sets of 62 and 42 kDa HABP receptors on RBCs and that peptide 26235 had at least two different sets of 77 and 62 kDa. HABPs inhibited in vitro merozoite invasion by between 54% and 94% at 200 microM, suggesting that these RAP2 peptides are involved in the in vitro P. falciparum invasion process.

Amino Acid Sequence↗
PubMed2004

Identification of Plasmodium falciparum reticulocyte binding protein RBP-2 homologue a and b (PfRBP-2-Ha and -Hb) sequences that specifically bind to erythrocytes.

Plasmodium falciparum reticulocyte binding protein RBP-2 homologues a and b (PfRBP-2-Ha and -Hb) have been described as being high molecular weight proteins, expressed at the P. falciparum merozoite apical extreme, belonging to a family of proteins found in other Plasmodium involved in the search for erythrocyte populations before being invaded by merozoites. 185, 20-mer-long non-overlapping peptides, spanning the entire PfRBP-2-Ha and -Hb sequences, were synthesised, radiolabelled and tested in erythrocyte binding assays. Fifteen PfRBP-2-Ha and -Hb high binding activity peptides (HBAPs) specifically binding to erythrocytes with high affinity were identified. Dissociation constants were between 70 and 300 nM and Hill coefficients were 1 approximately. HBAPs residues critical for binding to erythrocytes were determined. Cross-linking was performed allowing possible receptors for PfRBP-2-Ha and -Hb to be identified on the surface of the erythrocytes. Some of the HABPs showed merozoite invasion inhibition greater than 90% in in vitro assays.

Amino Acid Sequence↗
PubMed2004

Analysis and evaluation of periodic physiological organ motion in radiotherapy treatments.

BACKGROUND AND PURPOSE: A system for the detection, measurement and analysis of the periodic physiological organ motion during radiotherapy treatment is proposed and clinically tested in this paper. MATERIAL AND METHODS: The procedure is based on the acquisition of fluoroscopic sequences, followed by an automatic detection of the movement using cross-correlations with matched filters. RESULTS: The system generates a probability density function (PDF) of finding a mobile organ in a position at a certain time. The maximum path of the mobile structures can be determined to define the planning target volume (PTV) without ambiguities. CONCLUSIONS: Physiological movements can be accurately included in the daily planning routine, which is not essentially modified, without needing previous patient training.

Automation↗
PubMed2003

P. falciparum: merozoite surface protein-8 peptides bind specifically to human erythrocytes.

This work determined Plasmodium falciparum merozoite surface protein-8 (MSP-8) regions specifically binding to membrane surface receptors on human erythrocytes. Five high activity binding peptides (HABPs), whose binding to erythrocytes became saturable and sensitive on being treated with neuraminidase and chymotrypsin were identified from the MSP-8 protein. Those amino acids directly involved in interaction with erythrocytes were also determined for each one of the HABPs. Some of them specifically recognized 28, 46, and 73 kDa erythrocyte membrane proteins. Some HABPs inhibited in vitro P. falciparum merozoite invasion of erythrocytes by up to 98%, suggesting the MSP-8 protein's possible role in the invasion process.

Amino Acid Sequence↗
PubMed2003

Plasmodium falciparum normocyte binding protein (PfNBP-1) peptides bind specifically to human erythrocytes.

Plasmodium falciparum normocyte binding protein-1 (PfNBP-1), a Plasmodium vivax RBP-1 orthologue is expressed in the apical merozoite area. PfNBP-1 binds directly to human erythrocyte membrane in a sialic acid-dependent but trypsin-resistant way. Erythrocyte binding assays were done with synthetic peptides covering the sequence reported as PfNBP-1. Two specific erythrocyte high activity binding peptides were found: 101VFINDLDTYQYEYFYEWNQ(120), peptide 26332, and 181NTKETYLKELNKKKMLQNKK(200), peptide 26336. These two peptides' binding was saturable and presenting nanomolar affinity constants. The critical binding residues (those residues underlined and highlighted in bold) were determined by competition assays with glycine-scan analogue peptides. These peptides were able to block merozoite in vitro invasion of erythrocytes.

Amino Acid Sequence↗
PubMed2003

[Role of linezolid in antimicrobial therapy].

The progressive emergence of multi-resistant gram-positive strains has prompted the search for new molecules (quinolones, streptogramins, oxazolidinones, ketolides, glycopeptides, daptomycin) to add to the current therapeutic arsenal. Linezolid, the first commercially available member of the oxazolidinone family, has evidenced activity against multi-resistant gram-positive strains (methicillin-resistant Staphylococcus aureus, S. aureus with decreased glycopeptide sensitivity, vancomycin-resistant Enterococcus spp., Streptococcus pneumoniae with decreased sensitivity to penicillin and cephalosporins), thereby providing a new option for treating infections by these microorganisms. This work reviews the microbiologic and pharmacologic aspects of this agent in order to establish its position among the available options for antimicrobial chemotherapy.

Acetamides↗
PubMed2002

Building blocks for the solution phase synthesis of oligonucleotides: regioselective hydrolysis of 3',5'-Di-O-levulinylnucleosides using an enzymatic approach.

A short and convenient synthesis of 3'- and 5'-O-levulinyl-2'-deoxynucleosides has been developed from the corresponding 3',5'-di-O-levulinyl derivatives by regioselective enzymatic hydrolysis, avoiding several tedious chemical protection/deprotection steps. Thus, Candida antartica lipase B (CAL-B) was found to selectively hydrolyze the 5'-levulinate esters, furnishing 3'-O-levulinyl-2'-deoxynucleosides 3 in >80% isolated yields. On the other hand, immobilized Pseudomonas cepacia lipase (PSL-C) and Candida antarctica lipase A (CAL-A) exhibit the opposite selectivity toward the hydrolysis at the 3'-position, affording 5'-O-levulinyl derivatives 4 in >70% yields. A similar hydrolysis procedure was successfully extended to the synthesis of 3'- and 5'-O-levulinyl-protected 2'-O-alkylribonucleosides 7 and 8. This work demonstrates for the first time application of commercial CAL-B and PSL-C toward regioselective hydrolysis of levulinyl esters with excellent selectivity and yields. It is noteworthy that protected cytidine and adenosine base derivatives were not adequate substrates for the enzymatic hydrolysis with CAL-B, whereas PSL-C was able to accommodate protected bases during selective hydrolysis. In addition, we report an improved synthesis of dilevulinyl esters using a polymer-bound carbodiimide as a replacement for dicyclohexylcarbodiimide (DCC), thus considerably simplifying the workup for esterification reactions.

Burkholderia cepacia↗
PubMed2002

Plasmodium vivax MSP-1 peptides have high specific binding activity to human reticulocytes.

Plasmodium vivax merozoites have high preferential ability to interact with and invade reticulocytes, although these cells correspond to only 2% of the red blood cells (RBC) population. P. vivax merozoite surface protein-1 (Pv-MSP-1) is believed to have an important role in attachment and invasion process. Using 88 non-overlapping 20-mer peptides, covering the entire Pv-MSP-1 Belem strain sequence, RBC and reticulocyte binding assays were performed. Fourteen sequences were identified with high specific binding activity to reticulocytes, but only three had high specific binding activity to mature erythrocytes. These peptides showed affinity constant values between 20 and 150nM, indicating a strong interaction between these sequences and reticulocyte receptors. Critical residues in binding to reticulocytes for these peptides were determined by competition binding assays with glycine scanning analogues. All high binding peptides bind to reticulocyte surface proteins having a molecular mass of around 18-20kDa which are not present in mature RBC. Interestingly, some high activity binding peptides (HABPs) are located close to the hypothesised 42 and 19kDa fragment cleavage sites for this protein, suggesting that these sequences have an important role in target cell attachment and invasion process by Pv-MSP-1.HABPs may be clustered in two regions, with region I being located between amino acids 280-719, and region II between amino acids 1060-1599 with higher than 25% identity level. A P. falciparum MSP-1 antigenic domain binds to RBCs and inhibits parasite invasion. Peptides 1721 and 1724 bind with high activity to reticulocytes in homologous Pv-MSP-1, suggesting similar functions for these two sequences.

Amino Acid Sequence↗
PubMed2002

Identification and polymorphism of Plasmodium vivax RBP-1 peptides which bind specifically to reticulocytes.

Plasmodium vivax merozoite preferentially invades reticulocytes probably using PvRBP-1 as ligand. One hundred and ninety-five, 15-mer peptides has been synthesised from PvRBP-1 sequence; tested in reticulocyte- or erythrocyte-binding assays. Twenty-five peptides (K(d)=76-380 nM) specifically defined four reticulocyte-binding regions. It has been reported that a highly conserved Region-I recombinant fragment binds specifically to reticulocytes. HABP-critical residues for reticulocyte-binding were highly conserved in 20 Colombian P. vivax clinical isolates, suggesting an important biological function. There were six overlapping reticulocyte-binding sites for these peptides according to enzyme sensitivity and mutual competition-binding assays; located on 26- and 41-kDa reticulocyte membrane surface proteins.

Animals↗
PubMed2002

Randomized prospective comparison between erythropoietin and androgens in CAPD patients.

BACKGROUND: Anemia and malnutrition are significant complications in peritoneal dialysis (PD) patients. Previous studies in hemodialysis have shown that androgens are effective as therapy for anemia; however, this has not been tested in a randomized prospective trial in PD patients. Furthermore, the anabolic properties of androgens may exert additional benefits on the nutritional status in this population. METHODS: Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis (CAPD) therapy were randomized to receive recombinant human erythropoietin (rHuEPO; N = 14) or nandrolone decanoate (ND; 200 mg/week IM; N = 13) as therapy for anemia. The evolution of hematologic parameters and the impact on both nutritional anthropometric and biochemical variables were evaluated after six months of treatment. RESULTS: Hemoglobin and hematocrit experienced similar increases in both groups: from 8.5 +/- 0.9 g/dL and 25.8 +/- 2.7% to 11.7 +/- 0.6 g/dL and 34.7 +/- 1.6% (P < 0.001) in patients receiving rHuEPO, and from 8.9 +/- 0.8 and 27 +/- 2.2% to 11.8 +/- 0.4 g/dL and 35.1 +/- 1.5% (P < 0.001) in subjects treated with ND. At the end of the study, out of the diverse nutritional variables included in this investigation, only weight and body mass index significantly increased in the rHuEPO group. Conversely, both anthropometric [weight, body mass index, triceps skinfold, mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum total proteins, albumin, prealbumin and transferrin) were significantly increased in patients treated with ND. In this group, serum urea nitrogen, urea net excretion and protein equivalent of nitrogen appearance significantly decreased. These facts, together with an increase in serum creatinine and no changes in dietary intake during the study, suggest a rise in muscle mass related to an anabolic effect of nandrolone decanoate. Interestingly, serum levels of insulin-like growth factor type 1 (IGF-1) increased in patients on the androgen group compared to subjects treated with rHuEPO. Moreover, there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin, hematocrit, MAC and MAMC. CONCLUSIONS: Androgens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO. Furthermore, compared with rHuEPO, androgen administration was associated with beneficial effects on nutritional status. The mechanism of action of androgens on hematologic and nutritional parameters might be mediated, at least in part, by IGF-1.

Aged↗