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Biomedical subjects

L Ruiz

Publications and source records attributed to L Ruiz.

At least 19 recordsLinked to original sources

Crystallochemistry, textural properties, and in vitro biocompatibility of different silicon-doped calcium phosphates.

Three silicon-doped calcium phosphates (Si-CaPs) were synthesized by heating precipitated silicon-doped apatite via different thermal treatments. Temperatures of 700 degrees C, 900 degrees C, and 1100 degrees C led to an apatite-glass biphasic material, nanocrystalline Si-doped apatite (SiHA), and Si-doped apatite-alpha tricalcium phosphate biphasic material, respectively. Structure, microstructure, textural properties, and chemical differences were determined for the three bioceramics. Biocompatibility tests were carried out by seeding osteblast-like cells onto the three substrates. Si-CaP treated at 700 degrees C and 900 degrees C led to Ca decrease in the culture media, partially impeding the cell proliferation over them. However, the proliferation capability is restored when additional culture medium is added. Finally, cytotoxicity results indicated that cell damage is much lower in osteblast-like cells seeded onto SiHA and SiHA-alpha tricalcium phosphate samples than in plastic culture control.

Biocompatible Materials↗

Treatment of monocytes with interleukin (IL)-12 plus IL-18 stimulates survival, differentiation and the production of CXC chemokine ligands (CXCL)8, CXCL9 and CXCL10.

During inflammation, interleukin (IL)-12 and IL-18 are produced by macrophages and other cell types such as neutrophils (IL-12), keratinocytes and damaged endothelial cells (IL-18). To explore the role of IL-12 and IL-18 in inflammatory innate immune responses we investigated their impact on human peripheral blood monocytes and mature bronchoalveolar lavage (BAL) macrophages. IL-12 and IL-18 together, but not alone, prevented spontaneous apoptosis of cultured monocytes, promoted monocyte clustering and subsequent differentiation into macrophages. These morphological changes were accompanied by increased secretion of CXC chemokine ligands (CXCL)9, CXCL10 (up to 100-fold, P < 0.001) and CXCL8 (up to 10-fold, P < 0.001) but not CCL3, CCL4 or CCL5. Mature macrophages (from BALs) expressed high basal levels of CXCL8, that were no modified upon stimulation with IL-12 and IL-18. In contrast, the basal production of CXCL9 and CXCL10 by BALs was increased by 10-fold (P < 0.001) in the presence of either IL-12 or IL-18 alone and by 50-fold in the presence of both cytokines. In conclusion, our results indicate a relevant role for IL-12 and IL-18 in the activation and resolution of inflammatory immune responses, by increasing the survival of monocytes and by inducing the production of chemokines. In particular, those that may regulate angiogenesis and promote the recruitment of monocytes, activated T cells (CXCL9 and CXCL10) and granulocytes (CXCL8).

Analysis of Variance↗

Genetic characterization of Anaplasma (Ehrlichia) platys in dogs in Spain.

This paper reports the first genetic characterization of Anaplasma (Ehrlichia) platys in Spain from a naturally infected dog. The dog presented clinical signs compatible with canine ehrlichiosis. After DNA extraction and PCR amplification, 16S rRNA gene and citrate synthase gene ( gltA) of this agent were amplified. The GenBank accession number for the nucleotide sequence of the 16S rRNA gene of this strain is AY530806. The A. platys strains registered in France and Japan showed the highest similarity to the 16S rRNA gene sequence obtained from the Spanish strain. In the amplification of the gltA gene, a 1443 bp fragment was obtained, and three nucleotide differences were detected in comparison with other strains sequences. These data confirm the presence of A. platys in a dog showing clinical signs compatible with ehrlichiosis in Spain.

Anaplasma↗

Absence of a coding region for the helper component-proteinase in the genome of cucumber vein yellowing virus, a whitefly-transmitted member of the Potyviridae.

The complete nucleotide sequence of isolates of Cucumber vein yellowing virus (CVYV) has been determined. The viral genome comprises 9734 nucleotides, excluding a 3'-terminal poly(A) sequence. The genome of CVYV has a 5'-non coding and a 3' non coding region of respectively 67 and 240 nucleotides. The RNA of CVYV encodes a single polyprotein of 3148 amino acid residues and has a deduced genome organization and motifs typical for a member of the family Potyviridae. However, CVYV is atypical because it lacks a coding sequence region for the putative helper-component as well as conserved helper-component-proteinase motifs which may account for its vector relations. All the present coding regions were compared to those from several members of the Potyviridae family. CVYV is most closely related to Sweetpotato mild mottle virus confirming its assignation to the genus Ipomovirus, despite similarities with tritimoviruses.

Animals↗

Heat requirement for the onset of the Olea europaea L. pollen season in several sites in Andalusia and the effect of the expected future climate change.

Olives are one of the largest crops in the Mediterranean region, especially in Andalusia, in southern Spain. A thermal model has been developed for forecasting the start of the olive tree pollen season at five localities in Andalusia: Cordoba, Priego, Jaen, Granada and Malaga using airborne pollen and meteorological data from 1982 to 2001. Threshold temperatures varied between 5 degrees C and 12.5 degrees C depending on bio-geographical characteristics. The external validity of the results was tested using the data for the year 2002 as an independent variable and it confirmed the model's accuracy with only a few days difference from predicted values. All the localities had increasingly earlier start dates during the study period. This could confirm that olive flower phenology can be considered as a sensitive indicator of the effects of climate fluctuations in the Mediterranean area. The theoretical impact of the predicted climatic warming on the olive's flowering phenology at the end of the century is also proposed by applying Regional Climate Model data. A general advance, from 1 to 3 weeks could be expected, although this advance will be more pronounced in mid-altitude inland areas.

Climate↗

Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation.

We describe five female carriers of the FMR1 premutation who presented with symptoms of tremor and ataxia and who received a diagnosis of definite or probable fragile-X-associated tremor/ataxia syndrome (FXTAS). Unlike their male counterparts with FXTAS, none of the women had dementia. Females had not been reported in previous studies of FXTAS, suggesting that they may be relatively protected from this disorder. Brain tissue was available from one of the five subjects, a women who died at age 85 years; microscopic examination revealed intranuclear neuronal and astrocytic inclusions, in accord with the findings previously reported in males with FXTAS. The work-up of families with the FMR1 mutation should include questions regarding neurological symptoms in both older male and female carriers, with the expectation that females may also manifest the symptoms of FXTAS, although more subtly and less often than their male counterparts.

Adult↗

Drotrecogin alfa (activated) prevents smoke-induced increases in pulmonary microvascular permeability and proinflammatory cytokine IL-1beta in rats.

In an established rat model of smoke inhalation injury, we conducted a dose-response study to examine the protective effects of Xigris [drotrecogin alfa (activated) (DrotAA)], a recombinant form of human activated protein C (APC). DrotAA is a serine protease (approximately 55 kD molecular weight) with the same amino acid sequence and the glycosylation site as human plasma-derived APC. A total of 120 F344/NH rats (half each gender, approximately 175 g body weight) were randomly divided into five groups and exposed nose-only to air or diesel fuel smoke for 20 min. These rats were then i.v. administered with DrotAA in 0, 5, 10, and 20 mg/kg body weight, respectively, immediately following smoke exposure. Treatment with DrotAA significantly attenuated smoke inhalation injury in a dose-dependent manner at 2 hours after insult, as indicated by preserving microvascular permeability and proinflammatory cytokine IL-1beta (but not TNF-alpha and neuropeptide substance P) in bronchoalveolar lavage fluid (BALF). Moreover, the rats treated with 20 mg/ kg of DrotAA had an improvement of the expiration phase of pulmonary dynamic compliance. At all dosages, however, DrotAA also significantly increased all phases of pulmonary resistance compared with either the controls or to smoke inhalation alone. Generally, these data suggest that DrotAA may exert an anti-inflammatory effect by inhibiting cytokine-mediated inflammatory amplification. However, additional studies following a clinical course are needed to confirm the maximum efficiency and possible side effects of this recombined human activated protein C.

Animals↗

Differential expression of the cytokine receptors for human interleukin (IL)-12 and IL-18 on lymphocytes of both CD45RA and CD45RO phenotype from tonsils, cord and adult peripheral blood.

The objective of this study was to demonstrate the variable expression of cytokine receptors on naive versus memory human CD4+ T cell subpopulations in tonsillar tissue, cord blood and adult blood. We prove that the receptors for both interleukin (IL)-12 and IL-18 are expressed exclusively on memory T cells. This observation was seen not only on the CD45RO+ memory T cells but also on a significant percentage of the CD45RA+, CD62L-, CD27- and CCR7- populations. Furthermore, CD45RA+ CD62L+, CD27+ or CCR7+ CD4+ T cells that expressed IL-12Rbeta1 and IL-18Ralpha did not express CD31, a marker for recent thymic emigrants. We reveal that cord blood lymphocytes do not express IL-12Rbeta1 whereas IL-18Ralpha expression was detected at low levels. Importantly, the IL-12Rbeta2 signalling chain, which is absent in all resting T cells, was up-regulated in both CD45RA+ and CD45RO+ T cells as a result of stimulation with anti-CD3 and anti-CD28 in vitro. This observed up-regulation was, however, restricted to 80% of the total CD4+ population. Finally, a very small proportion of the CD4+ CD45RO+ tonsillar T cells expressed the IL-12 and IL-18 receptors, thereby establishing the differential expression of these receptors between peripheral and tonsillar memory T cell subpopulations.

Adolescent↗

Laparoscopic radical nephrectomy for T1 renal cancer: the gold standard? A comparison of laparoscopic vs open nephrectomy.

OBJECTIVE: To evaluate the complication rate and clinical follow-up of patients treated for T1 renal cancer by open or laparoscopic nephrectomy at the same institution, as this approach appears to be attractive for treating small renal cancers. PATIENTS AND METHODS: Between 1995 and 2002, 39 patients underwent retroperitoneal laparoscopic and 26 transperitoneal open radical nephrectomy for T1 renal cancer (TNM 1997). Variables before during and after surgery, e.g. cancer recurrence, were compared between the groups. RESULTS: There were no differences between the laparoscopic and open groups in age, sex ratio, weight, height, fitness score, operative duration (134 vs 133 min), minor or major complications, tumour diameter, Fuhrman grade or length of follow-up. Patients who underwent laparoscopic surgery had less blood loss (133 vs 357 mL, P < 0.001), less need for transfusion (none vs 150 mL, P = 0.04), a lower consumption of analgesia drugs, and shorter hospitalization (5.5 vs 8.8 days, P < 0.001). With a mean follow-up of 20.4 months there was no recurrence or tumour progression. CONCLUSION: Laparoscopic radical nephrectomy for patients with T1 renal cancer is a safe, reliable procedure that decreases hospitalization time and bleeding, and ensures the same cancer control as open nephrectomy.

Adult↗

Updated European recommendations for the clinical use of HIV drug resistance testing.

In most European countries, HIV drug resistance testing has become a routine clinical tool. However, its practical implementation in a clinical context is demanding. The European HIV Drug Resistance Panel was established to make recommendations to clinicians and virologists on this topic and to propose quality control measures. The panel recommends resistance testing for the following indications: i) drug-naive patients with acute or recent infection; ii) therapy failure, including suboptimal treatment response, when treatment change is considered; iii) pregnant HIV-1-infected women and paediatric patients with detectable viral load when treatment initiation or change is considered; and iv) genotype source patient when post-exposure prophylaxis is considered. In addition, for drug-naive patients with chronic infection in whom treatment is to be started, the panel suggests that resistance testing should be strongly considered and recommends testing the earliest sample for drug resistance if suspicion of resistance is high or prevalence of resistance in this population exceeds 10%. The panel does not favour genotyping over phenotype, however it is anticipated that genotyping will be used more often because of its greater accessibility, lower cost and faster turnaround time. For the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible. It is mandatory that laboratories performing HIV resistance tests take regular part in quality assurance programs. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and meet regularly to discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. The panel also encourages the timely collection of epidemiological information to estimate the impact of transmission of resistant HIV and the prevalence of HIV-1 non-B subtypes in the different European countries.

Anti-HIV Agents↗

Coffee drinking: the rationale for treating it as a potential effect modifier of carcinogenic exposures.

Clinical and epidemiological studies on cancer etiology seldom treat coffee drinking as a potential effect modifier. Yet caffeine exerts significant effects upon a large variety of physiologic, cellular and molecular systems. Caffeine, 'the world's most popular drug', is also a fundamental research tool, widely used in clinical studies on drug metabolism, and in experimental studies on cell cycle checkpoints, DNA repair, and apoptosis, among many other. Caffeine can profoundly alter cell cycle checkpoint function and several mechanisms of DNA repair, as well as carcinogen metabolism. The impact of caffeine on cell cycle checkpoint function occurs in spite of it being nonmutagenic in traditional mutagenesis assays. A complex body of biologic evidence suggests that caffeine-containing beverages can both enhance and antagonise potentially carcinogenic exposures. However, most pathways leading to the ultimate effects in human beings remain unknown. It is unclear whether any of the hundreds of compounds contained in coffee and tea exert a direct and significant carcinogenic effect per se in any human tissue at usual conditions of use. Reasons exist to consider that coffee may sometimes be an indirect, positive confounder. The study of interactions between caffeine-containing beverages and environmental agents in well defined groups of healthy and diseased people could yield new insights into checkpoint signal transduction and other mechanisms of carcinogenesis. Information on the use of caffeine-containing beverages should more often be integrated in studies on the role of gene-environment interactions in the pathogenesis of cancer.

Coffee↗

Antibiotic susceptibility patterns for environmental streptococci isolated from bovine mastitis in central California dairies.

Environmental streptococci are frequently isolated from bovine mastitis in dairy cows with only limited information available on the antimicrobial susceptibility of these organisms. A total of 362 environmental streptococci isolated from cases of bovine mastitis from the central San Joaquin Valley of California over a 3-yr period were used in the study. Overall, 39.9% of the strains tested were Streptococcus uberis, 42.2% were Streptococcus dysgalactiae, and 11.1% were Enterococcus spp. The antimicrobial susceptibility for these organisms was determined for the following antimicrobial agents: penicillin, ampicillin, cephalothin, ceftiofur, penicillin + novobiocin, erythromycin, pirlimycin, tetracycline, and sulfadimethoxine. Results demonstrate substantial differences in the susceptibility patterns for the various organisms collectively referred to as the environmental streptococci. The MIC90 for penicillin was 0.06 microg/ml for 152 strains of S. dysgalactiae compared with 0.25 microg/ml for 133 strains of S. uberis. However, the Enterococcus spp. were the most resistant organisms tested. These data also indicate that the use of interpretive criteria based on human data may provide misleading results. In conclusion, these data confirm that the environmental streptococci are a diverse group of organisms comprised of several different genera and species and that identification of environmental streptococci to the species level is needed to appropriately modify control methods. Moreover, the use of the agar disk diffusion (Kirby-Bauer) susceptibility test for agents with human-based interpretive criteria is contraindicated, and these tests should only be performed with agents with mastitis specific interpretive criteria.

Animals↗

Changes in the rate of genotypic resistance to antiretroviral drugs in Spain.

Genotypic resistance to antiretroviral drugs was examined in 684 individuals attending 18 outpatient clinics distributed across Spain in June 2000. Compared with similar surveys conducted before 1998, the prevalence of resistance to nucleosides has declined significantly among naive chronic HIV carriers. In contrast, resistance among pre-treated patients has increased; resistance to all three drug families having been recognized in nearly a quarter of patients.

Anti-HIV Agents↗

Psychological impact of structured treatment interruptions in patients with prolonged undetectable HIV-1 viral loads.

Structured treatment interruption strategies may help overcome problems of highly active antiretroviral therapy, but might also represent a cause of stress. We present data that indicate a psychological benefit from structured treatment interruption. Although some disturbances appear at the resumption of therapy, no definitive problems are found that preclude such therapeutic approaches from a psychological perspective. However, a close follow-up of patients during interruption periods is advisable to avoid difficulties reported at treatment resumption presenting a risk to patients' health.

Antiretroviral Therapy, Highly Active↗

Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.

BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.

Adult↗

HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection.

OBJECTIVE: To evaluate whether controlled re-exposures to autologous HIV-1 could boost HIV-specific immunity and limit virus replication in patients with chronic HIV-1 infection. PATIENTS AND DESIGN: Subjects with at least 2 years virus suppression during antiretroviral therapy and a CD4 : CD8 ratio > 1 were randomly assigned to interrupt highly active antiretroviral treatment (HAART) three times (n = 12) or to continue their previous HAART (n = 14). RESULTS: In 10/12 interrupter patients a rebound of HIV-1 RNA was detected in all three structured treatment interruptions (STI). Plasma virus doubling time was shorter during the first STI than in the second and third STI, corresponding to an average 13% reduction in viral basic reproductive rate. However, the mean time before plasma viral load rose to > 50 copies/ml was significantly shorter in the second and third STI. The average frequency of HIV-specific CD8 T cells in the interrupter patients at the end of the third STI cycle was significantly higher compared with the baseline and the end of the first STI. A substantial increase in HIV-specific CD8 T cell frequencies was found in four interrupter patients, whereas there were no changes in all 14 non-interrupter individuals. A weak p24-specific T helper response developed in 5/12 interrupter patients compared with no response in non-interruptors, but these responses were transient and disappeared rapidly. CONCLUSION: The increase in the control of viral replication, and positive effects of STI on immune responses in this population should encourage the further development of HIV-specific immune-based therapeutic strategies.

Adult↗