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Biomedical subjects

C Alonso

Publications and source records attributed to C Alonso.

373 records · Page 21Linked to original sources

Liposomes as alternative vehicles for sun filter formulations.

The aim of our study was to determine the influence of several types of liposomes with a different lipid composition on the percutaneous absorption of one conventional sun filter with a lipophilic character (ethyl hexyl methoxycinnamate) using both in vitro and in vivo methodologies. Three different liposomes were prepared with unsaturated and saturated phosphatidylcholine (PC, HPC), and with a wool lipid mixture (IWL) with a composition similar to that of the stratum corneum lipids. Results showed that the liquid crystalline state associated with PC liposomes plays a key role in enhancing skin penetration. when liposomes with a composition and structural organization similar to that of the stratum corneum lipids (HPC and IWL) are used, the skin penetration is retarded, suggesting a certain reinforcement of the stratum corneum barrier. These two types of liposomes could be regarded as alternatives to conventional oil/water emulsions in the formulations of lipidic sun filters. Finally, an acceptable correlation was obtained using both in vitro and in vivo methodologies to evaluate the corresponding skin absorption profile.

Animals↗

Adjuvant guided polarization of the immune humoral response against a protective multicomponent antigenic protein (Q) from Leishmania infantum. A CpG + Q mix protects Balb/c mice from infection.

It has been shown that vaccination with three doses of the Leishmania infantum poly-protein Q containing five genetically fused antigenic determinants from the Lip2a, Lip2b, H2A and P0 proteins, mixed with BCG induces clearance of parasites in 9 out of 10 Leishmania infantum-infected Beagle dogs, in addition to clinical protection. In the present paper we analysed the immunogenic potential of the poly-protein Q and the specificity and polarization of the response against the antigenic determinants of Q when mixed with various adjuvants. The data showed that the Q protein had high intrinsic immunogenic potential and that it was able to induce a long-lasting IgG response. The IgM immunogenic potential of the poly-protein was mainly due to the LiP2a and LiP2b determinants, whereas the IgG immunogenic potential was mainly due to the LiP2a component. It was observed that the protein itself elicited a mixed IgG2a/IgG1 response and that the determinants of Q were endowed with different IgG2a/IgG1 potential. It was also observed that the adjuvants did not influence the intensity or specificity of the IgM response but that they modulated the intensity, the specificity and the polarization of the IgG response against the determinants of Q. CpG-ODN motifs or double-stranded DNA plasmids containing CpG motifs when mixed with Q induced a predominant IgG2a response mainly observed at early stages post-immunization. The data showed that a CpG + Q mix induced significant protection against L. infantum infection in Balb/c mice.

Adjuvants, Immunologic↗

Cytokine-driven inflammatory response is associated with the hypermetabolism of AIDS patients with opportunistic infections.

BACKGROUND: To assess a possible role of systemic inflammation in the resting metabolic response in AIDS patients with active secondary infections. METHODS: Fifty-two patients with AIDS-defined criteria and concomitant active infections and 19 healthy subjects were studied. Measurements were as follows: body composition assessed by bioelectrical impedance; resting energy expenditure (REE) by 30-minute indirect calorimetry; cytokine concentrations (IL-6, IFNalpha, TNFalpha, sTNF-R1) by ELISA; C-reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, and nutritional parameters by standard techniques. RESULTS: REE adjusted for fat-free mass (REEFFM) was significantly increased in AIDS patients despite 39% of them not being hypermetabolic. The patients were undernourished and were found to have increased levels of acute-phase proteins and increased concentrations of IL-6 and sTNF-R1 relative to controls. REE parameters were positively related to CRP, ESR, ferritin, IL-6, and sTNF-R1 and negatively related to albumin, prealbumin, and transferrin. CRP was an independent predictor of REEFFM in AIDS patients and explained 25% of its variability. Patients with severe inflammation (CRP > or = 37 mg/dL) were significantly hypermetabolic with respect to patients without inflammation (CRP < 6 mg/dL) and had higher levels of IL-6 and sTNF-R1 and lower levels of albumin and prealbumin. Although no significant differences were observed with respect to the infection type, patients with tuberculosis and Pneumocystis carinii infections had higher resting metabolic and inflammatory responses, whereas patients with recurrent bacterial pneumonia were normometabolic and had lower levels of inflammatory markers. CONCLUSIONS: Resting hypermetabolism observed in AIDS patients with concurrent active infections is related to the presence and severity of systemic cytokine-driven inflammatory response, which could reflect the type of secondary infection.

AIDS-Related Opportunistic Infections↗

Towards the physical map of the Trypanosoma cruzi nuclear genome: construction of YAC and BAC libraries of the reference clone T. cruzi CL-Brener.

Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome have to capitalize on three main advantages of the parasite genome, namely (a) its small size, (b) the fact that all chromosomes can be defined, and many of them can be isolated by pulse field gel electrophoresis, and (c) the fact that simple Southern blots of electrophoretic karyotypes can be used to map sequence tagged sites and expressed sequence tags to chromosomal bands. A major drawback to cope with is the complexity of T. cruzi genetics, that hinders the construction of a comprehensive genetic map. As a first step towards physical mapping, we report the construction and partial characterization of a T. cruzi CL-Brener genomic library in yeast artificial chromosomes (YACs) that consists of 2,770 individual YACs with a mean insert size of 365 kb encompassing around 10 genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs) have been constructed, BACI and BACII. Both libraries represent about three genome equivalents. A third BAC library (BAC III) is being constructed. YACs and BACs are invaluable tools for physical mapping. More generally, they have to be considered as a common resource for research in Chagas disease.

Animals↗

Genes and chromosomes of Leishmania infantum.

During recent years, several Leishmania infantum genes have been cloned and characterized. Here, we have summarized the available information on the gene organization and expression in this protozoan parasite. From a comparative analysis, the following outstanding features were found to be common to most of the genes characterized: tandemly organized genes with conserved coding regions and divergent untranslated regions, polycistronic transcription and post-transcriptional regulation of gene expression. The analysis of chromosomes of L. infantum by pulsed-field electrophoresis showed the existence of both size and number polymorphisms such that each strain has a distinctive molecular karyotype. Despite this variability, highly conserved physical linkage groups exists among different strains of L. infantum and even among Old World Leishmania species. Gene mapping on the L. infantum molecular karyotype evidenced a bias in chromosomal distribution of, at least, the evolutionary conserved genes.

Animals↗

Molecular and antigenic characterization of the Leishmania (Viannia) panamensis kinetoplastid membrane protein-11.

The kinetoplastid membrane protein 11 (KMP-11) has been recently described in Leishmania (Leishmania) donovani as a major component of the promastigote membrane. Two oligonucleotide primers were synthesized to PCR-amplify the entire encoding region of New World Leishmania species. The Leishmania (Viannia) panamensis amplification product was clone, sequenced and the putative amino acid sequence determined. A remarkably high degree of sequence homology was observed with the corresponding molecule of L. (L) donovani and L. (L) infantum (97% and 96%, respectively). Southern blot analysis showed that the KMP-11 locus is conformed by three copies of the gene. the L. (V) panamensis ORF was subsequently clone in a high expression vector and the recombinant protein was induced and purified from Escherichia coli cultures. Immunoblot analysis showed that 80%, 77% and 100% sera from cutaneous, mucocutaneous and visceral leishmaniasis patients, respectively, recognized the recombinant KMP-11 protein. In a similar assay, 86% of asymptomatic Leishmania-infected individuals showed IgG antibodies against the rKMP-11. We proposed that KMP-11 could be used as a serologic marker for infection and disease caused by Leishmania in America.

Animals↗

[Effect of supragingival plaque control on subgingival microflora and periodontal tissues].

The aim of this study was to investigate, clinically and microbiologically, forty-four sites in 11 patients presenting with generalized chronic periodontitis. Plaque Index (PI), Gingival Index (GI), Probing Bleeding (PB), Probing Depth (PD) and Insertion Level (IL) were registered. Samples of subgingival plaque were collected in the same sites for cultivation of anaerobic bacteria and determination of microbiological morphotypes using dark field microscopy. Clinical and microbiological data were recorded on the baseline and 4 weeks after the adoption of a program to control supragingival plaque and calculus. The microbiological analysis categorized the degree of development as follows: 0--not detected, 1--scarce, 2--moderate and 3--abundant. The clinical results at the baseline and on the 28th day were, respectively: PI--1.73 +/- 0.10 and 0.30 +/- 0.08; GI--1.73 +/- 0.08 and 1.41 +/- 0.08; PB--0.91 +/- 0.04 and 0.59 +/- 0.07; PD--6.43 +/- 0.20 and 5.77 +/- 0.25; and IL--6.86 +/- 0.32 and 6.52 +/- 0.34. There was significant decrease in PI, GI, PB and PD. However, the difference in IL was not significant. The relative proportions of the microbial morphotypes observed under dark field microscopy at the baseline and on the 28th day were, respectively: coccoid cells--21.16 +/- 3.77 and 36.00 +/- 4.66; mobile bacillus--44.86 +/- 2.65 and 39.50 +/- 2.64; and total treponemes--24.66 +/- 3.08 and 19.25 +/- 2.75. The cultures presented, at the baseline and on the 28th day, respectively: Prevotella intermedia/nigrescens (Pi/n)--1.36 +/- 0.18 and 0.43 +/- 0.11; Porphyromonas gingivalis--0.48 +/- 0.16 and 0.32 +/- 0.13; Actinobacillus actinomycetemcomitans--0.23 +/- 0.09 and 0.23 +/- 0.10; Fusobacterium nucleatum--0.32 +/- 0.14 and 0.41 +/- 0.13; and peptostreptococci--0.82 +/- 0.19 and 0.54 +/- 0.16. There was a significant increase in the number of coccoid cells and a decrease in the number of treponemes and Pi/n.

Adult↗

[Ultrasonic decalcification of the aortic valve. Initial experience].

We report our initial experience in 2 patients with degenerative calcific aortic stenosis who underwent ultrasonic debridement of the aortic valve. Compared with preoperative studies, doppler echocardiographic and hemodynamic evaluation before hospital discharge revealed a reduction in the mean aortic valve pressure gradient (80 and 65 mmHg to less than 10 mmHg). There was no change in aortic regurgitation grade. Follow-up doppler echocardiographic evaluation at four and six months showed no changes in gradient or regurgitation in the comparison to the postoperative data. Long-term results will show the convenience to attempt or not ultrasonic salvage of the native aortic valve in severe calcific stenosis.

Aged↗

Prevalence of HLA-B27 and subtypes of HLA-B27 associated with ankylosing spondylitis in Galicia, Spain.

OBJECTIVE: To assess the prevalence of HLA-B27 and its subtypes in both the normal population and in patients with Ankylosing Spondylitis (AS) in Galicia, Northwest Spain. METHODS: The prevalence of HLA-B27 in the normal population was determined by checking the number of HLA-B27 positive samples in 308 subjects from different areas of Galicia who had donated organs over a period of 4 years. A total of 106 patients with the diagnosis of AS, according to the modified New York clinical criteria for definitive ankylosing spondylitis, were collected from three very representative areas of Galicia. HLA-B27 was determined by PCR using the primers E91s and E136as, while 11 subtypes of HLA-B27 were analyzed using a commercial kit. RESULTS: The prevalence of HLA-B27 in organ donors was 9.34%. HLA-B27 was present in 94.3% of patients with AS. Subtypes B*2701, B*2709 and B*2710 were not found. The subtypes found in the normal population were; B*2705 (79.5%), B*2702 (18%) and B*2708 (2.5%). The subtypes associated with AS were B*2705 (88%) and B*2702 (12%). CONCLUSION: The prevalence of HLA-B27 in Galicia was 9.34%, which is higher than previously published in Spain. The frequency of the subtypes associated with AS was similar to that reported for other Spanish regions.

DNA↗

[Long-term experience with flexible mitral annuloplasty].

Reconstructive surgery of the mitral valve is nowadays generally accepted to be a valid alternative to replacement. There is however little information on the long term stability of these techniques and specially the incidence of reoperation. In order to study this question all patients who had a Durán flexible ring annuloplasty performed between january 1975 and december 1976 were reviewed up to december 1987. Eighty seven flexible rings were placed in 85 patients. Aortic and/or tricuspid surgery was simultaneously performed in 44.8% of the patients. There were 2 hospital deaths (2.3% ) and 3 late deaths (3.5%). Ten patients were lost to follow up, all within 2 years after surgery. There were 18 thromboembolic events (11 central and seven peripheral) with one death. Thirteen patients required reoperation (17.8%) In 11 the valve was replaced and a new flexible ring annuloplasty was done in two, without mortality. The causes for reoperation were regurgitation in eight (10.9%) and stenosis in five (5.8%). When the lesion was regurgitant the average interval between operations was 20.6 months, and when stenotic of 87.8 months. It can be concluded that reconstructive surgery of the mitral valve, in this predominantly rheumatic group of patients, has an incidence or reoperation close to 18% at 12-13 years follow up.

Adolescent↗

p53 oncoprotein as a prognostic indicator in patients with breast cancer.

UNLABELLED: p53 is a tumor suppressor gene located on the human chromosome 17 that is thought to regulate (suppress) the proliferation of normal cells. The mutant protein accumulates in the nuclei of tumor cells that may then have a proliferative advantage over normal cells. The purpose of this study was to investigate the relationship between levels of mutant p53 expression and the clinical outcome of patients with node-positive and node-negative breast cancer. Expression of mutant p53 was evaluated in 655 human breast carcinomas (349 node-positive and 306 node-negative patients) with long-term clinical follow-up by immunohistochemistry in sections from paraffin embedded tumors. RESULTS: Immunoreactivity was found in 37.3% of breast tumors. There was no significant correlation between the expression of p53 and tumor size, nodal involvement, age or histological type. However, p53 overexpression was clearly related to histological grade and steroid receptors, with a trend to higher overexpression in ER-tumors or in those with a high histological grade (p < 0.01). On univariate analysis positive tumors were associated with reduced DFS in the total group (p < 0.001) as well as in node-positive patients (p < 0.05) and in node-negative patients (p < 0.01). In conclusion, these results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance in both node-positive and node-negative patients.

Biomarkers, Tumor↗