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Biomedical subjects

J Navarro

Publications and source records attributed to J Navarro.

At least 109 records · Page 6Linked to original sources
PubMed2000

The pathophysiology of endometriosis-associated infertility: follicular environment and embryo quality.

Several retrospective analyses of IVF and oocyte donation programmes, performed to gain clinical knowledge of the factors implicated in the aetiology of endometriosis-associated infertility, have demonstrated that the quality of the embryo is affected in patients with endometriosis. To understand the mechanisms of this alteration, the endocrine, paracrine and autocrine conditions induced during folliculogenesis in women with and without endometriosis were investigated. The first approach was to study ovarian steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and hCG-stimulated granulosa cell cultures. It is proposed that the pattern of progesterone secretion may be related to changes in the release of cytokines by ovarian and white blood cells. Hence, a second trial measured interleukin 1 (IL-1), IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were higher in the natural cycles of women with endometriosis than in women in the control group, and were modulated by ovarian stimulation, decreasing significantly in serum from stimulated cycles. In addition, IL-6 concentrations were higher in the follicular fluid of women with endometriosis than in those in the control group and IL-6 was released in higher amounts by granulosa luteal cells of patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of patients with endometriosis. These observations indicate that infertility in patients with endometriosis may be related to alterations within the follicle which, in turn, result in oocytes and embryos of lower quality, as demonstrated in the IVF programme. In addition, these embryos have a reduced ability to implant, as observed in the oocyte donation model. These alterations may be induced by functional changes in the process of folliculogenesis that affect steroid synthesis, as well as by cytokine release by ovarian and blood cells.

Embryo Transfer↗
PubMed2000

[Digestive and nutritional management of adults with cystic fibrosis].

Digestive disturbances are frequent in adults with cystic fibrosis. They can lead to malnutrition which in turn is deleterious to the prognosis. We summarise the information on epidemiology, pathogenicity, signs, diagnostic criteria and treatments of exocrine pancreatic insufficiency, gastro-oesophageal reflux and denutrition (which are all frequent) but also of constipation, rectal prolapse, distal intestinal obstruction syndrome, and liver diseases. The main recommendations are the following: 1--know how to treat pancreatic insufficiency with enzyme replacement and vitamins; 2--know how to treat aggressively any gastro-esophageal reflux; 3--diagnose and treat denutrition as early as possible; 4--know the distal intestinal obstruction syndrome to avoid abusive and dangerous surgery; 5--know that the most severe hepatic diseases can be treated by liver transplantation.

Adult↗
PubMed2000

[Pediatric nosocomial diarrhea].

Nosocomial diarrhea are an important cause of childhood morbidity and mortality. Rotavirus has been recognized as the most important cause of nosocomial gastroenteritidis particularly in infants during winter months. Nosocomial diarrhea are also, caused by bacterial pathogen like Clostridium difficile, Salmonella, Shigella, Campylobacter. Clostridium difficile toxin assay should be considered for patients who are receiving antibiotics. Modifications of hygiene procedures and preventive measures are necessary in order to reduce nosocomial infection.

Adenoviridae Infections↗
PubMed1999

[Dynamics of immunoglobulin production in non infected children born from HIV-1 infected mothers: effect of zidovudine].

BACKGROUND: To evaluate the possible effect of zidovudine (ZDV) on inmunoglobins production in infants born to HIV-1 infected women. SUBJECTS AND METHODS: We have studied the immunoglobulins serum levels in 57 non-infected children born to HIV-infected mothers. The children were divided into two groups: group A, 28 children born to HIV-1 infected mothers that received ZDV on protocol 076 conditions, and group B, 29 children born to mothers that did not receive anti-HIV-1 drugs. Quantification of serum IgG, IgA and IgM was performed by nephelometric techniques. RESULTS: The median time to reach normal IgA values at 12 months, was 25.57 months (confidence interval [CI] 95%: 22.01-29.12) in the children of group A and 12.67 months (CI 95%: 9.90-15.44) in the children of group B (p = 0.01). The median time to reach normal IgM values at 12 months was 15.93 months (CI 95%: 15.21-16.65) in group A children versus 11.20 months (CI 95%: 8.51-13.89) in group B (p = 0.11). The median time to reach normal IgG values at 12 months was 19.67 months (CI 95%: 13.12-16.22) in group A children versus 12.73 months (CI 95%: 11.16-14.30) in group B (p = 0.05). The normal IgA levels were reached 2.36 (CI 95%: 1.16-4.81) times later in group A than in group B children (p = 0.02), whereas normal IgG levels were reached 1.88 (CI 95%: 0.94-3.78) times later in group A than in group B of children. CONCLUSIONS: Our results indicate that treatment of pregnant mothers with ZDV clearly affect the ability of their newborns to produce inmunoglobulins, which may have important practical implications for their vaccination protocols.

Anti-HIV Agents↗
PubMed1999

Differential mechanisms of recognition and activation of interleukin-8 receptor subtypes.

We have probed an epitope sequence (His18-Pro19-Lys20-Phe21) in interleukin-8 (IL-8) by site-directed mutagenesis. This work shows that single and double Ala substitutions of His18 and Phe21 in IL-8 reduced up to 77-fold the binding affinity to IL-8 receptor subtypes A (CXCR1) and B (CXCR2) and to the Duffy antigen. These Ala mutants triggered neutrophil degranulation and induced calcium responses mediated by CXCR1 and CXCR2. Single Asp or Ser substitutions, H18D, F21D, F21S, and double substitutions, H18A/F21D, H18A/F21S, and H18D/F21D, reduced up to 431-fold the binding affinity to CXCR1, CXCR2, and the Duffy antigen. Interestingly, double mutants with charged residue substitutions failed to trigger degranulation or to induce wild-type calcium responses mediated by CXCR1. Except for the H18A and F21A mutants, all other IL-8 mutants failed to induce superoxide production in neutrophils. This study demonstrates that IL-8 recognizes and activates CXCR1, CXCR2, and the Duffy antigen by distinct mechanisms.

Antigens, CD↗
PubMed1999

PU.1 regulates the CXCR1 promoter.

The interleukin-8 receptors (CXCR1 and CXCR2) are specifically expressed at high levels in cells of the neutrophil lineage. In this work we identify promoter elements of the CXCR1 gene and the ets family transcription factor PU.1 as a major regulator for activation of the CXCR1 promoter. We first showed that the upstream sequence of CXCR1 (-800 to +86 base pairs (bp)) directs myeloid-specific expression of reporter gene constructs. Second, we showed the presence of negative elements in the sequence from -800 to -128 bp and positive elements from -128 to +50 bp. Third, we demonstrated that the fragment -22 to +14 bp binds PU.1. Fourth, we showed that PU.1 transactivates the CXCR1 promoter. These data are the first demonstration of PU.1-mediated transcriptional regulation of a neutrophil chemoattractant G protein-coupled receptor.

Animals↗
PubMed1999

Diagnosis of tuberculosis in children using a polymerase chain reaction.

We investigated the value of the polymerase chain reaction (PCR) in the diagnosis of active tuberculosis in children and evaluated the relationship between PCR results in children with tuberculous infections and mediastinal adenopathies detected by computerized tomography (CT-Scan). This was a controlled, blinded, prospective study comparing nested PCR, mycobacterial cultures and the clinical diagnosis based on 350 clinical specimens from 117 children referred for evaluation of suspected pulmonary tuberculosis. All children with tuberculous infection but without active disease underwent a chest CT-scan to detect the presence of mediastinal adenopathies not evident on chest x-ray. The sensitivity of PCR was 56.8% in children with clinically active disease (culture: 37.8%; smears: 13.5%). A major advantage of PCR over cultures was noted when there was no parenchymal involvement on chest radiograph and when the patient was undergoing anti-tuberculous treatment. There were nine specimens with false-negative PCR results due to the presence of amplification reaction inhibitors. PCR was positive in five children with tuberculous infection without active disease and these children presented mediastinal adenopathies on the CT-scan that were not evident on chest radiography. There were no false-positive PCR results in the control groups of children. We conclude that nested PCR is a rapid and sensitive method for the early diagnosis of tuberculosis in children. It is especially useful when the diagnosis of active tuberculosis is difficult. In our study children with tuberculous infection without apparent disease who have positive PCR results have mediastinal adenopathies on CT-scan.

Child↗
PubMed1999

Influence of dietary nucleotides on plasma immunoglobulin levels and lymphocyte subsets of preterm infants.

We examined the effects of nucleotide supplementation to a preterm adapted milk formula on the lymphocyte subsets and plasma IgG, IgM and IgA levels in preterm infants for the first three months of life. Two groups of preterm infants received a milk formula or the same formula supplemented with CMP, AMP, UMP, GMP and IMP to mimic the concentration of acid-soluble nucleotides found in human milk. Blood samples were obtained at birth, 10 days, 20-30 days and 3 months of age. Preterm infants fed the nucleotide formula exhibited higher plasma levels of IgM in all postnatal study periods than neonates fed the standard formula; moreover, IgA was also higher at 3 months of age in nucleotide formula fed infants. No major differences were seen between groups for IgG levels and lymphocyte subsets. Thus, dietary nucleotides appear to exert actions on immature human neonate lymphocytes enhancing the in vivo production of Ig which may have a role in the defense capacity of neonates.

Aging↗
PubMed1999

Changes in glutathione status and the antioxidant system in blood and in cancer cells associate with tumour growth in vivo.

The relationship among cancer growth, the glutathione redox cycle and the antioxidant system was studied in blood and in tumour cells. During cancer growth, the glutathione redox status (GSH/GSSG) decreases in blood of Ehrlich ascites tumour-bearing mice. This effect is mainly due to an increase in GSSG levels. Two reasons may explain the increase in blood GSSG: (a) the increase in peroxide production by the tumour that, in addition to changes affecting the glutathione-related and the antioxidant enzyme activities, can lead to GSH oxidation within the red blood cells; and (b) an increase of GSSG release from different tissues into the blood. GSH and peroxide levels are higher in the tumour cells when they proliferate actively, however GSSG levels remain constant during tumour growth in mice. These changes associate with low levels of lipid peroxidation in plasma, blood and the tumour cells. The GSH/GSSG ratio in blood also decreases in patients bearing breast or colon cancers and, as it occurs in tumour-bearing mice, this change associates with higher GSSG levels, especially in advanced stages of cancer progression. Our results indicate that determination of glutathione status and oxidative stress-related parameters in blood may help to orientate cancer therapy in humans.

Animals↗
PubMed1999

Cytokines in older patients undergoing in vitro fertilization: the relationship to the response to controlled ovarian hyperstimulation.

PURPOSE: Our purpose was to assess the endocrine, autocrine, and paracrine milieu in follicles of older women undergoing stimulated cycles, comparing normal (NR) and low (LR) responses, based on the measurement of interleukin (IL)-1 beta, IL-6, and vascular endothelial growth factor (VEGF) in serum and follicular fluid (FF). METHODS: A total of 40 women entered the study, divided into three groups: (1) older patients (> 37 years) with NR (age-NR; n = 18); (2) older women with LR (age-LR; n = 11); and (3) normal controls, aged < 35 years (control; n = 11). IL-1 beta, IL-6, and VEGF measured in serum (day of ovum pickup) and FF, employing ELISAs. RESULTS: Follicular fluid IL-6 was significantly (P < 0.05) higher in age-LR compared to the other two groups. IL-6 and VEGF showed a 4- to 20-fold increase in FF compared to blood, suggesting the ovary as an additional source of both cytokines. IL-1 beta levels remained unchanged in FF compared to blood and, also, among groups. CONCLUSIONS: These data provide further evidence that the endocrine, paracrine, and/or autocrine status in vivo of older patients is different from that of younger women and suggest that cytokines, specifically IL-6, may be involved in the changes observed during senescence within the ovary.

Adult↗
PubMed1999

Maturation in vitro of human oocytes from unstimulated cycles: selection of the optimal day for ovum retrieval based on follicular size.

The potential use of immature oocytes for in-vitro fertilization (IVF) requires the conditions for successful maturation to be defined. This study focused on the day of oocyte retrieval. The selection of a dominant follicle may induce endocrine changes in the remaining cohort that may be detrimental to their subsequent fertilization and embryonic development. Natural cycles in volunteer donors were followed by measurement of serum oestradiol and by vaginal ultrasound, starting on day 3 of the cycle. Cycles were randomly allocated to one of two groups: group 1 (n = 10), in which follicles were aspirated before the leading follicle was 10 mm in diameter; and group 2 (n = 9), in which follicles were aspirated when a dominant follicle was clearly visible with diameter >10 mm. Oocytes were cultured in vitro to metaphase II (MII) stage, donated, and inseminated by intracytoplasmic sperm injection (ICSI) with husband's spermatozoa. Those that became fertilized within 24 h were further co-cultured in autologous endometrial epithelial cells up to the blastocyst stage, and cryopreserved. There was a significantly (P < 0.05) increased rate of oocyte retrieval in group 1 (70.8% of aspirated follicles) compared with group 2 (50.5%). Maturation to MII and fertilization were similar between the groups. However, development to blastocyst stage was significantly (P < 0.05) higher in group 1 embryos (56.5%) compared with group 2 (35.7%). There was a positive correlation (r2 = 0.1978) between the appearance of the cumulus cells and the ability to develop to blastocyst stage when both parameters were analysed in group 1, whereas no such correlation was found in group 2. In conclusion, our data suggest the importance of retrieving immature oocytes before follicular selection, and define the conditions for the first stage in the use of immature oocytes. Further stages must be defined before this technique can be used clinically.

Adult↗
PubMed1999

Structural biology of chemokine receptors.

Chemokine receptors are G protein-coupled receptors that mediate migration and activation of leukocytes as an important part of a protective immune response to injury and infection. In addition, chemokine receptors are used by HIV-1 to infect CD4 positive cells. The structural bases of chemokine receptor recognition and signal transduction are currently being investigated. High-resolution X-ray diffraction and NMR spectroscopy of chemokines indicate that all these peptides exhibit a common folding pattern, in spite of its low degree of primary-sequence homology. Chemokines' functional motifs have been identified by mutagenesis studies, and a possible mechanism for receptor recognition and activation is proposed, but high-resolution structure data of chemokine receptors is not yet available. Studies with receptor chimeras have identified the putative extracellular domains as the major selectivity determinants. Single-amino acid substitutions in the extracellular domains produce profound changes in receptor specificity, suggesting that motifs in these domains operate as a restrictive barrier to a common activation motif. Similarly HIV-1 usage of chemokine receptors involve interaction of one or more extracellular domains of the receptor with conserved and variable domains on the viral envelope protein gp 120, indicating a highly complex interaction. Elucidating the structural requirements for receptor interaction with chemokines and with HIV-1 will provide important insights into understanding the mechanisms of chemokine recognition and receptor activation. In addition, this information can greatly facilitate the design of effective immunomodulatory and anti-HIV-1 therapeutic agents.

CD4-Positive T-Lymphocytes↗
PubMed1999

[Primary infection in vertically infected HIV-1 infants: biological characteristics of isolated virus, viral load and CD4 t-lymphocytes].

OBJECTIVE: Our aim was to study the relationship between virological and/or immunological markers during the first month of life in vertically HIV-1 infected infants without prior antiviral treatment. PATIENTS AND METHODS: Thirty HIV-1 infected infants that had not received prior antiviral therapy, nor had their mother during pregnancy, were studied. Viral load was quantified using standard molecular assays. Viral isolation and phenotype were carried out by using viral co-cultures. Subpopulations of lymphocytes were determined by flow cytometry. RESULTS: We have found an inverse correlation between log10 CD4+ cells/mm3, as well as CD4+ percentage with log10 viral load, with a slope of -0.266 (CI95%: -0.459 to -0.074) and -6.648 (CI95%: -12.815 to -0.471), respectively. When the influence of viral phenotype on the log10 viral load or the percent of CD4+ T cells standardized according to age (Z-score) with the log10 of the viral load was determined, it was found that infants having syncytium inducing (SI) virus had 12.355% (CI95%: 2.336 to 22.373) less CD4+ cells and 4.530 standard deviations (IC95%: 0.448 to 8.613) than infants with non syncytium inducing (NSI) isolates. CONCLUSIONS: Our results suggest that a particular biological phenotype of viral isolates (SI and those with rapid/high replication) and high plasma viral loads have a statistically significant tendency to be associated. Viral load is the marker that shows the best inverse correlation with the level of CD4+ cells normalized according to the infant's age. This correlation shows a different value in infants with SI and NSI isolates.

CD4-Positive T-Lymphocytes↗
PubMed1998

Gene delivery systems: Bridging the gap between recombinant viruses and artificial vectors.

Although most research in the field of somatic gene therapy has investigated the use of recombinant viruses for transferring genes into somatic target cells, various methods for nonviral gene delivery have also been proposed. Both types of gene delivery systems have advantages and drawbacks. Schematically, viral vectors are particularly efficient for gene delivery, whereas nonviral systems are free of the difficulties associated with the use of recombinant viruses but need to be further optimized to reach their full potential. In order to bridge the gap between viral vectors and synthetic reagents, we discuss here some specific features of the viral vector systems of today that could advantageously be taken into account for the design of improved nonviral gene delivery systems. Indeed, although nonviral systems differ fundamentally from viral systems, one possible approach towards enhanced artificial reagents aims at developing 'artificial viruses' that mimic the highly efficient processes of viral infection.

Journal Article↗
PubMed1998

CXC chemokines suppress proliferation of myeloid progenitor cells by activation of the CXC chemokine receptor 2.

IL-8 is one of the major mediators of the transendothelial migration of neutrophils from the circulation to the site of injury and infection. In this work we demonstrate that the CXC or alpha-chemokines, IL-8 and melanoma growth stimulatory activity (MGSA) induce myeloid suppression via direct action on progenitor cells, mediated by activation of the murine homologue of the CXC chemokine receptor-2 (CXCR2) or IL-8R B. We first show that proliferation of the IL-3-dependent murine myeloid progenitor cell line 32D is suppressed by human IL-8 and the functionally and structurally related peptide, MGSA. Second, we show for the first time the high endogenous expression of the murine CXCR2 in 32D cells, as demonstrated by Northern blot analysis, binding to [125I]macrophage inflammatory protein-2, and macrophage inflammatory protein-2-induced calcium responses in 32D cells. Third, we demonstrate that IL-8 and MGSA induce a rise in intracellular calcium in 32D cells. The IL-8-induced Ca2+ response is desensitizing, since a second dose of IL-8 did not trigger a second calcium response. Other chemokines, including neutrophil-activating protein-2, platelet factor-4, RANTES, and macrophage chemotactic protein-1, neither suppressed the proliferation of 32D cells nor induced a rise in intracellular calcium. Finally, the IC50 of IL-8- and MGSA-dependent suppression of proliferation of 32D cells is in good agreement with the EC50 of IL-8- and MGSA-dependent activation of neutrophil Mac-1 up-regulation and chemotaxis. Our studies are consistent with the idea that IL-8 and MGSA suppress the proliferation of 32D cells by activation of murine CXCR2.

Animals↗