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Biomedical subjects

J Peña

Publications and source records attributed to J Peña.

At least 19 recordsLinked to original sources

sHLA-G levels in the monitoring of immunosuppressive therapy and rejection following heart transplantation.

The aim of this study was to further determine the immediate influence, over a 12-h period, after the initiation of daily immunosuppressive treatment on the serum levels of sHLA-G in heart transplant patients during the post-transplant period (1 month). It was found that there are two patterns of patients in term of the changes observed in their levels of sHLA-G in response to the immunosuppressive treatment. One group (group A) showed no changes on sHLA-G while the other group (group B) a significant rise in sHLA-G levels was observed at 2 to 4 h post dose. Interestingly, it was observed that the patients in group B have better prognosis of acceptance of the heart graft than those of group A. On the other hand it was found that the patients with high levels of sHLA-G (77.3+/-34.8 ng/ml) in pre-transplant sera have a better prognosis of acceptance of the heart graft than those with low sHLA-G levels (9.7+/-7.1 ng/ml). In conclusion, both the intensity of changes of sHLA-G levels induced by immunosuppression and basal levels in pre-transplant could be used in the monitoring of the immunosuppression as well as the heart transplant evolution.

Acute Disease↗

Room temperature synthesis of agarose/sol-gel glass pieces with tailored interconnected porosity.

An original shaping technique has been applied to prepare porous bodies at room temperature. Agarose, a biodegradable polysaccharide, was added as binder of a sol-gel glass in powder form, yielding an easy to mold paste. Interconnected tailored porous bodies can be straightforwardly prepared by pouring the slurry into a polymeric scaffold, previously designed by stereolitography, which is subsequently eliminated by alkaline dissolution at room temperature. The so obtained pieces behave like a hydrogel with an enhanced consistency that makes them machinable and easy to manipulate. These materials generate an apatite-like layer when immersed in a simulated body fluid, indicating a potential in vivo bioactivity. The proposed method can be applied to different powdered materials to produce pieces, at room temperature, with various shapes and sizes and with tailored interconnected porosity.

Biocompatible Materials↗

Soluble HLA-G in heart transplantation: their relationship to rejection episodes and immunosuppressive therapy.

The aims of this study were to quantify the level of soluble HLA-G in heart transplant patients, to determine the relationship between the sHLA-G levels and the appearance of acute rejection episodes, and to identify the influence of immunosuppressive therapy on sHLA-G levels. Analysis of sHLA-G, measured by enzyme-linked immunosorbent assay in the transplant patients, revealed the existence of two similarly sized groups of patients. One group displayed a significant increase (p < 0.001) in sHLA-G during the first month after transplantation while the other group maintained low levels of the molecule (0-30 ng/ml) throughout the study. The latter group displayed a high incidence of recurrent severe rejection. A significant increase (p < 0.01) in sHLA-G 2 hours after administration of immunosuppressive treatment (mycophenolate mofetil, cyclosporine A/FK506, corticoids) was found. These results suggest that sHLA-G participates in the induction of certain levels of immunological tolerance in these recipients.

Adolescent↗

New advances in coeliac disease: serum and intestinal expression of HLA-G.

Coeliac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA-DQ2 and HLA-DQ8, but as human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. Our aim was to investigate whether HLA-G, a gene located in the MHC class I region, and with important role in the induction of immunotolerance, may contribute to CD susceptibility. We demonstrated the expression of soluble HLA-G (sHLA-G) forms in intestinal biopsy and in serum of patients with CD. Indeed, all patients tested showed a positive expression of HLA-G in intestinal mucosa with different grade of immunoreaction. The serum levels of sHLA-G found in coeliac patients depend on the association with other diseases of autoimmune nature or genetics, and also depend on the transgressions in the diet with gluten ingested. The enhancer expression of sHLA-G in CD could be due as part of a mechanism to try restore the tolerance process towards oral antigens in a disease caused by loss of tolerance to dietary antigens and counteract the inflammation. In summary, in this paper, we demonstrate the association of CD with sHLA-G expression.

Biopsy↗

Bovine tuberculosis in wild boar (Sus scrofa), red deer (Cervus elaphus) and cattle (Bos taurus) in a Mediterranean ecosystem (1992-2004).

During the last 12 years, an increasing frequency in condemnation of hunted red deer and wild boar carcasses due to the presence of tubercle-like lesions has been observed in Extremadura (Western Spain). Before 1993, tuberculosis was a very rare finding in hunted animals. The current tuberculosis regional prevalence in cattle approaches 0.4% after years of expensive test and slaughter campaigns. It is imperative to investigate the epidemiology of Mycobacterium bovis infection in red deer and wild boar in order to keep a good health status and to maintain the effectiveness of domestic species TB eradication programs. The present paper evaluates the problem in Sierra de San Pedro, estimating the prevalence of TB in wild boar and red deer, the main wild artiodactyls in the area, and domestic cattle since 1992-2004, by the use of a low-cost surveillance method based on detailed pathological inspection of hunted animal carcasses. Microbiology and molecular epidemiology studies on several M. bovis isolates from domestic and wild animals helped to define the interspecies contacts. These findings, as well as recent history of game estates management and descriptive epidemiology field work, throw light on the rise and maintenance of these epizootics.

Animals↗

Improved surgical mesh integration into the rat abdominal wall with arginine administration.

Prosthetic meshes are used as the standard of care in abdominal wall hernia repair. However, hernia recurrences and side effects remain unsolved problems. The demand by health care providers for increasingly efficient and cost-effective surgery encourages the development of newer strategies to improve devices and outcomes. Here, we evaluated whether l-arginine administration was able to ameliorate long-term polypropylene prostheses incorporation into the abdominal wall of Sprague-Dawley rats. Meshes were placed on-lay and continuous l-arginine was administered. In vivo biocompatibility was studied at 7, 25 and 30 days post-implantation. Effectively, l-arginine administration in combination with mesh triggered subtle changes in ECM composition that impinged on critical biochemical and structural features. Lastly, tensile strength augmented and stiffness decreased over the control condition. This could help to restructure the mechanical load transfer from the implant to the brittle surrounding tissues, i.e., impact load and fatigue load associated with mechanical tensions could be distributed between the mesh and the restored tissue in a more balanced manner, and ultimately help to reduce the incidence of loosening, recurrences, and local wound complications. Since the newly formed tissue is more mechanically stable, this approach could eventually be introduced to human hernia repair.

Abdominal Wall↗

PK and PK/PD of doxycycline in drinking water after therapeutic use in pigs.

A commercial doxycycline formulation was administered in drinking water to 12 pigs at the recommended dose of 10 mg/kg daily for 5 days. The mean plasma concentration at steady-state was 1.37 +/- 1.21 microg/mL, which was reached at 68 +/- 27.2 h postadministration. Absorption and elimination half-life values were 7.20 +/- 2.42 and 7.01 +/- 2.10 h, respectively. Most plasma concentrations during dosing were higher than the minimum inhibitory concentrations (MICs) described for the main porcine bacterial pathogens of the respiratory tract (Pasteurella multocida, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica and Mycoplasma hyopneumoniae). It is concluded that when pigs were treated with doxycycline in drinking water at the recommended rate, therapeutically effective concentrations were achieved throughout the treatment period, supporting the clinical use of this tetracycline in the control of respiratory infections. However, inter-animal differences were marked.

Actinobacillus pleuropneumoniae↗

Effect of the M(s) transformation temperature on the wear behaviour of NiTi shape memory alloys for articular prosthesis.

The main objective of this work has been the characterisation and correlation of the wear behaviour of the NiTi shape memory alloys in their different phases. The weight losses for the different alloys in function of the present phase, and of the M(s) transformation temperature are studied. Adhesive wear tests, Pin-on-Disk, according to the ASTM-G99 standard have been carried out. The thermoelastic martensitic transformations that cause the super-elastic effect, the reorientation and coalescence of martensitic plates and the damping effect promotes a high ability to accommodate large deformations without generating permanent damages that causes the wear. The resulting plastic deformation may be accumulated during wear process without generating fracture. The results show that the wear resistance is mainly dependent of the M(s) transformation temperature for both alloys. For the NiTi alloys also the Ni atomic percentage and the hardness of the alloys are important parameters in the wear behavior.

Alloys↗

Keratocyte injury in human corneas cryopreserved under standard conditions.

This study was conducted to characterize ultrastructural damage to human corneas cryopreserved by a standard protocol. The materials used were seven human corneas that were unsuitable for transplantation due to the presence of positive bacteriological cultures; they were cryopreserved according the standard procedure. After freezing and thawing, samples were obtained for scanning and transmission electron microscopy studies. Marked damage was observed in keratocytes with signs of apoptotic cellular injury. However our observations have shown that apoptosis contribute less significantly than necrosis to cellular death in keratocytes of human corneas and although the control of apoptosis is clearly desirable, in order to improve the success of cryopreserved corneas for transplant, we need to continue our investigation to reduce the effects of the necrotic process.

Cornea↗

Microstructural, mechanical and citotoxicity evaluation of different NiTi and NiTiCu shape memory alloys.

Transformation temperatures and mechanical properties such as transformation stresses at different temperatures and the superelasticity have been investigated in NiTiCu alloys with various Copper concentrations. The results have been compared with the conventional NiTi alloys. The addition of copper was effective to narrow the stress hysteresis and to stabilize the superelasticity characteristics. Moreover, it produced greater stability on both the transformation temperatures and the forces applied to the different tissues. However, the studies of cell cultured with human fibroblasts showed certain toxicity.

Biocompatible Materials↗

In vitro biocompatibility assessment of poly(epsilon-caprolactone) films using L929 mouse fibroblasts.

Biodegradable and biocompatible materials are the basis for tissue engineering. As an initial step for developing vascular grafts, the in vitro biocompatibility of poly(epsilon-caprolactone) (PCL), recently suggested for several clinical applications, was evaluated in this study using L929 mouse fibroblasts. Different cellular aspects were analyzed in order to know the cell viability during cell culture on PCL films: adhesion, proliferation, morphology, LDH release and mitochondrial function. Since topography and other surface characteristics of materials play an essential part in cell adhesion, PCL membranes with either smooth or rough surface were prepared, characterized and used to carry out cell cultures. During short culture times, PCL produced a significant stimulation of mitochondrial activity evaluated by reduction of the MTT reagent. The results provide evidences of good adhesion, growth, viability, morphology and mitochondrial activity of cells on PCL films. Therefore, it can be concluded that PCL is a suitable and biocompatible material as a scaffold for vascular graft development.

Animals↗

Continuous mandibular distraction osteogenesis using superelastic shape memory alloy (SMA).

Distraction osteogenesis is a well-established method of endogenous tissue engineering. It is a biological process of bone neo-formation between segments subjected to tension. The concept of this study was to investigate the distraction osteogenesis with a device capable of creating a permanent and constant force during the whole process as if a very large number of small elongations were applied constantly. The mechanical testing of the device used to produce the constant force and the in vivo analysis of the bone growth after it was implanted in rabbits are presented on this work. The device consists of a NiTi coil spring, superelastic at body temperature, in order to have a stress plateau during the austenitic retransformation during the unloading. The in vivo analysis was made on six female rabbits of 12 months old. A segmental mandibulectomy at the horizontal arm of the mandible and a corticotomy at 5mm distant from the gap were made. Next, following a latency period of five days, the SMA springs were implanted to induce the bone neo-formation. The displacement at the unloading plateau shows that it is necessary to have longer springs or to use several (available commercially) in series in order to fulfil the requirements of a human distraction. The temperature variations induced changes in the spring force. However, when the temperature returns to 37 degrees C the distraction force recovers near the initial level and does so completely when the distraction process continues. For the in vivo study, all six rabbits successfully completed the distraction. The radiographies showed the gap as distraction advanced. A continuity in the newly formed bone with similar transversal and horizontal dimensions than the original bone can be observed on the histologies. In conclusion, the application of a constant force on distraction osteogenesis, using SMA springs, may be a successful alternative to the conventional gradual distraction.

Animals↗

Role of the transmembrane domain of the VanT serine racemase in resistance to vancomycin in Enterococcus gallinarum BM4174.

Enterococcus gallinarum BM4175 (a vancomycin-susceptible derivative of BM4174 obtained by insertional inactivation of vanC-1) was transformed with plasmid constructs pCA10 (containing the genes necessary for resistance, vanC-1-XYc-T), pJP1 (with a fragment lacking the DNA encoding the transmembrane region of VanT, -vanC-1-XYc-T((Delta))(2-322)-) and with plasmids containing fragments encoding either the transmembrane (mvanT(1-322)) or racemase (svanT(323-698)) domains of VanT under the control of a constitutive promoter. Accumulated peptidoglycan precursors were measured in all strains in the presence of L-Ser, D-Ser (50 mM) or in the absence of any growth supplement. Uptake of 0.1 mM L-[(14)C]serine was also determined in BM4174, BM4175 and BM4175/pCA10. Vancomycin resistance was restored in BM4175 transformed with pCA10(C-1-XYc-T), and the profile of peptidoglycan precursors was similar to wild-type E. gallinarum BM4174. Transformation of E. gallinarum BM4175 with plasmid pJP1(vanC-1-XYc-T((Delta))(2-322)) resulted in: (i) vancomycin MICs remaining within susceptible levels (< or =4 mg/L) in the absence of any growth supplement, but increasing to 8 mg/L when either L-Ser or D-Ser was added to the medium; and (ii) the relative amounts of accumulated UDP-MurNAc-pentapeptide[D-Ser] and tetrapeptide precursors decreasing substantially compared with BM4175/pCA10 and BM4174. The effect on the appearance of tetrapeptide appeared to be host dependent, since a substantial amount was present when the same plasmid construct pJP1(vanC-1-XYc-T((Delta))(2-322)) was electroporated into Enterococcus faecalis JH2-2. The uptake of L-[(14)C]Ser at 240 s was decreased by approximately 40% in BM4175 compared with BM4174. Plasmid pCA10(C-1-XY(C)-T) restored uptake of L-[(14)C]Ser at 180 and 240 s in BM4175. The results suggest that the transmembrane domain of VanT is likely to be involved in the transport of L-Ser, and that in its absence the resistance phenotype is compromised.

Bacterial Proteins↗

[Evaluation of lercanidipine in the general practice setting].

OBJECTIVE: To determine the efficacy and tolerability of a long-acting dihydropyridine in the clinical settings of general practice. MATERIAL AND METHODS: 110 essential hypertensives were included (age 62.3 +/- 10.8 years, 51 men and 53 women, 38/ obese -IMC >30 kg/m2, ten diabetics). 104 patients ended the followup. Patients were treated with lercanidipine 10 mg once daily in the morning. Follow-up lasted 6 months. When blood pressure was not controlled (BP < 140/90 mmHg) in any visit, a second drug was added, excluding calcium channel blockers. Antiadrenergic drugs were recommended. If patients were not controlled ittwo consecutive visits they were excluded from follow-up. RESULTS: Significant reductions in both systolic (baseline 157.4 +/- 11.7 vs 131.1 +/- 6.8 mmHg, p < 0,001) and diastolic BP (baseline 94.7 +/- 5.8 vs 80.0 +/- 5.5 mmHg, p < 0,001) were attained at six months. Mean SBP decrease was 26.7 mmHg and mean DBP reduction was 15.6 mmHg. At the study end, 84.3/ of the patients achieved a BP < 140/90 mmHg. Thirty patients needed a second drug to become controlled (26 at the study end). The overall incidence of adverse effects was 4,4/ (n=6) and just three patients withdrew the treatment due to untoward effects. Plasmatic cholesterol lowered from 225.3 +/- 41.0 to 216.7 +/- 25.3 mg/dl (p = 0,03) and urate decreased from 5.6 +/- 1.6 to 5.1 +/- 1.4 mgldl, p = 0,03). CONCLUSIONS: Lercanidipine is a calcium channel blockers of high efficacy and low incidence of adverse effects in the clinical settings of general practice. It seems to have a positive metabolic effects on plasmatic levels of cholesterol and urate.

Aged↗

Distribution of HLA-DRB1 genes in patients with sporadic ankylosing spondylitis in the south of Spain.

OBJECTIVE: To evaluate the relationship between the presence of different HLA-DRB1 genes and predisposition to develop a sporadic form of ankylosing spondylitis (AS) in a demographically well-defined population. METHODS: One hundred fifteen selected patients with sporadic (non-familial) forms of AS from six different cities and 748 bone marrow donors as control group. All individuals were typed for HLA-B27 by flow cytometry with monoclonal antibodies and PCR -SSP, as well as for HLA-DRB using the Dynal ELI SSO HLA-DRB Test (Dynal AS, Oslo, Norway). The Inno-Lipa DRB Decoder (Innogenetics NV Zwijndrecht, Belgium), was used for high-resolution HLA-DRB typing. RESULTS: The presence of the DRB1*01 antigen in the studied population is significantiy higher in B27 positive healthy individuals (bone marrow donors) than in B27 positive AS patients; also, DRB1*01 is higher in B27 negative AS patients than 827 negative controls. The frequency of DRB1*03 is higher in B27 negative controls than B27 negative AS patients. CONCLUSION: The results of this study suggest that DRB1*01 antigens might be involved in the development of sporadic forms of ankylosing spondylitis in HLA-B27 negative individuals in the studied area.

Adult↗

Determination of aniline derivatives in oils related to the toxic oil syndrome by atmospheric pressure ionization-tandem mass spectrometry.

In 1981, an unknown disease appeared in Spain, the Spanish Toxic Oil Syndrome. Nowadays and despite all efforts, the etiological agent is still unknown. Early studies showed a link between this illness and the consumption of denatured rapeseed oil fraudulently processed and marketed as edible oil. Two families of aniline derivatives present in these oils (fatty acid anilides and acylated phenyl amino propanediol derivatives or PAPs) were found to be good chemical markers of toxic oils. In this work, a new method has been developed to analyze these aniline derivatives in oil samples by HPLC-MS and HPLC-MS/MS with an API source. For their quantification, three different internal standards were used, one for anilides and two for PAPs. Quantification limits were 8 ppm for anilides and 0.2 ppm for PAPs. Anilides and PAPs were found in marker-positive samples at levels up to 50,000 and 330 ppm, respectively. The relative abundance of the different fatty acid anilides and PAPs correlates with the fatty acid composition of the oils. More than 2,600 different samples were analyzed by this method in the most exhaustive screening of suspected toxic oils carried out to date.

Aniline Compounds↗

Altered expression of CD43-hexasaccharide isoform on peripheral T lymphocytes from HIV-infected individuals.

OBJECTIVE: To examine if peripheral T lymphocytes from HIV-infected individuals show abnormalities in the surface expression of CD43, the major sialoglycoprotein of leukocytes. DESIGN: A series of 86 HIV-positive individuals was studied. The subjects, grouped by their peripheral CD4 cell count, were in different stages of the disease as defined by the Centers for Disease Control and Prevention (CDC). METHODS: Peripheral leukocytes and isolated lymphocytes were examined by double and triple immunofluorescence flow cytometric and Western blot analyses with monoclonal antibodies, which discriminate between CD43 isoforms. RESULTS: We found elevated percentages of the surface expression of CD43-hexasaccharide isoform on T lymphocytes from 82 out of 86 individuals tested. Increasing percentages are progressively found in CDC groups 1, 2 and 3 patients. The expression of the molecule is remarkably biased towards the CD8 cell subpopulation. The percentage of cells bearing human leukocyte antigen-DR locus molecules (HLA-DR) is also augmented. Two subsets expressing T305 have been identified: a minor subset that co-expresses HLA-DR and T305; and a second population formed by the majority of T305-positive cells, which lack surface HLA-DR. Finally, we found CD43 bands with altered electrophoretic mobility in lysates from peripheral lymphocytes from all HIV-positive individuals tested. CONCLUSION: The augmented expression of CD43-hexasaccharides and the observed cellular distribution suggest an important regulatory role for this molecule in HIV-specific responses.

Antigens, CD↗