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Biomedical subjects

A Zúñiga

Publications and source records attributed to A Zúñiga.

At least 19 recordsLinked to original sources

Nosocomial outbreak of Pseudomonas aeruginosa infections related to a flexible bronchoscope.

An outbreak of Pseudomonas aeruginosa infections affecting 17 patients was detected in the 27-bed intensive care unit (ICU) of a community hospital from 1 July to 30 September 2003. An ambidirectional cohort study was conducted to identify the risk factors for infection. Nosocomial infections were defined using the criteria of the Centers for Disease Control and Prevention. Random arbitrary polymorphic DNA-polymerase chain reaction was used for genotypic characterization. Logistic regression analyses demonstrated that case patients were more likely than non-cases to have had a longer stay in the ICU, and to have undergone mechanical ventilation and antimicrobial treatment. The multi-variate analysis identified recent bronchoscopy [risk ratio (RR) 3.8, 95% confidence interval (CI) 2.5-3.9] and exposure to an infected patient (RR 2.9, 95% CI 1.1-3.7) as independent risk factors. Molecular analysis showed that of the nine isolates available, four patients had a similar strain. The factor with the strongest influence on the risk of death was infection with P. aeruginosa (RR 2.1, 95% CI 1.0-2.4, P=0.04). A combined infection control strategy was implemented, including strict compliance with isolation precautions and recommendations for cleaning and disinfecting bronchoscopes, and a sharp reduction in the incidence of P. aeruginosa infection followed. It is thought that this outbreak was caused by patient-to-patient transmission and infection from a common source, i.e. the flexible bronchoscope.

Bronchoscopes↗

Health care costs and financial consequences of epidemiological changes in chronic diseases in Latin America: evidence from Mexico.

OBJECTIVE: To determine the costs of health services and the financial consequences of changes in the epidemiological profile of chronic diseases in Latin America. STUDY DESIGN: We conducted longitudinal analyses of costs and of the economic impact of the epidemiological transition in healthcare services for diabetes and hypertension in the Mexican health system. The study population included both the insured and uninsured populations. METHODS: The cost-evaluation method was based on the instrumentation and consensus techniques. To estimate the epidemiological changes and financial consequences for 2004-2006, six models were constructed according to the Box-Jenkins technique, using confidence intervals of 95% and the Box-Pierce test. FINDINGS: Costs ranged from US$613 to US$887 for diabetes, and from US$485 to US$622 for hypertension. Regarding epidemiological changes for 2004 compared with 2006, an increase is expected in both cases, although results predict a greater increase for diabetes, 10-15% in all three institutions (P<0.05). Comparing the financial consequences of health services required by insured and uninsured populations, the greater increase (17%) will be for the insured population (P<0.05). The financial requirements for both diseases will amount to 9.5% of the total budget for the uninsured population and 13.5% for the insured population. CONCLUSIONS: If the risk factors and the different healthcare models remain as they are at present, the economic impact of expected epidemiological changes on the social security system will be particularly strong. Another relevant financial factor is the appearance of internal competition in the use and allocation of financial resources among the main providers in the health services; this factor becomes even more complicated within each provider. In effect, within each institution, hypertension and diabetes programmes must compete for resources with other programmes for chronic and infectious diseases.

Case Management↗

Coasting acts through downregulation of VEGF gene expression and protein secretion.

BACKGROUND: This study was conducted to investigate the mechanisms by which coasting may be effective in decreasing the incidence of ovarian hyperstimulation syndrome (OHSS). METHODS: A total of 160 women (patients and oocyte donors) undergoing coasting and 116 controls were included in the study. Serum, follicular fluid and granulosa cells were collected on the day of oocyte retrieval. Vascular endothelial growth factor (VEGF) concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to evaluate VEGF gene expression in granulosa cells. Cell death was studied by flow cytometry using annexin V-fluorescein isothiocyanate (FITC) and counterstaining by propidium iodide, and double staining with CD45 monoclonal antibody was performed to distinguish the contamination of apoptotic leukocytes. RESULTS: Follicular cells aspirated from coasted patients showed a ratio in favour of apoptosis, especially in smaller follicles (48 versus 26%, P < 0.05). Follicular fluid determinations confirmed that coasting reduces VEGF protein secretion (1413 versus 3538 pg/ml, P < 0.001) and gene expression (2-fold decrease) in granulosa cells. Follicular fluid VEGF protein levels positively correlated with follicular size (r = 0.594, P = 0.001) and estradiol production (r = 0.558, P = 0.038). Women who underwent coasting showed a comparable IVF cycle outcome; however, a higher cancellation rate was found in cycles that were coasted. CONCLUSIONS: Coasting affects all follicles through apoptosis, especially immature follicles, without affecting oocyte/endometrial quality. The significant decrease found in VEGF expression and secretion explains why coasting is clinically effective in reducing the incidence and severity of OHSS.

Down-Regulation↗

Extended coasting duration exerts a negative impact on IVF cycle outcome due to premature luteinization.

Coasting, or withholding gonadotrophin administration while maintaining gonadotrophin-releasing hormone analogue until oestradiol drops to a safe concentration, is an alternative approach to prevent ovarian hyperstimulation syndrome (OHSS) in high responder patients. However, the length of this procedure has not been precisely studied. This paper is a retrospective study of 132 patients who showed a high response (oestradiol > 4500 pg/ml and/or more than 20 follicles > 17 mm) to ovarian stimulation and were coasted due to their high risk of developing OHSS, and evaluated the impact of the duration of coasting on IVF cycle outcome. Additionally, serum LH and progesterone concentrations were studied to investigate whether premature luteinization was present in these cycles and whether it might be related to coasting duration. A significant decrease in implantation rate was found when coasting was required for more than 4 days, together with a trend towards a higher cancellation rate. Premature luteinization was significantly elevated in women undergoing coasting compared with control women (34 versus 15.6%, P < 0.05). In the majority of patients who showed premature luteinization, coasting lasted >/=3 days. To conclude, prolonged coasting may affect the endometrium, anticipating the implantation window. These data may explain why some women undergoing extended coasting show a lower implantation rate compared with controls.

Adult↗

Effects of strength training on muscle power and serum hormones in middle-aged and older men.

Effects of 16-wk strength training on maximal strength and power performance of the arm and leg muscles and serum concentrations [testosterone (T), free testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 +/- 2 yr) and 11 older men (M64; 64 +/- 2 yr). During the 16-wk training, the relative increases in maximal strength and muscle power output of the arm and leg muscles were significant in both groups (P < 0.05-0.001), with no significant differences between the two groups. The absolute increases were higher (P < 0.01-0.05) in M46 than in M64 mainly during the last 8 wk of training. No significant changes were observed for serum T and FT concentrations. Analysis of covariance showed that, during the 16-wk training period, serum FT concentrations tended to decrease in M64 and increase in M46 (P < 0.05). However, significant correlations between the mean level of individual serum T and FT concentrations and the individual changes in maximal strength were observed in a combined group during the 16-wk training (r = 0.49 and 0.5, respectively; P < 0.05). These data indicate that a prolonged total strength-training program would lead to large gains in maximal strength and power load characteristics of the upper and lower extremity muscles, but the pattern of maximal and power development seemed to differ between the upper and lower extremities in both groups, possibly limited in magnitude because of neuromuscular and/or age-related endocrine impairments.

Aged↗

A pea nuclear protein that is induced by dehydration belongs to the vicilin superfamily.

The purification to homogeneity of p16, a protein with an electrophoretic mobility compatible with an apparent molecular mass of 16 kDa, from nuclei of ungerminated pea embryonic axes is described. A cDNA clone of its gene, which was designated psp54, was also isolated. The psp54 cDNA contains an open reading frame coding for a 54.4-kDa polypeptide (p54). p16 corresponds to the C-terminal third of p54, although the mechanisms by which the primary polypeptide could be processed are not yet known. The sequence of p54 is 60% identical with that of the precursor of a sucrose-binding soybean protein, and, to a lesser extent (31-34%), it shares homology with some storage proteins. p16 is also 30% homologous with Nhp2p, a yeast nuclear protein. The psp54 gene, present in a single copy in pea genome, starts being expressed during seed desiccation. Soon after rehydration in seed germination, p54 mRNA disappears and is no longer detectable in vegetative tissues, except in response to hydric stress (exposure to abscisic acid, osmolites or desiccation). p16 can be recovered from nuclei cross-linked to histone H3, when the disulfide bridges that occur in vivo are preserved. On the other hand, p16 shares some properties with dehydrins, which are thought to protect cellular structures against desiccation. We propose that the possible precursor polypeptide p54 belongs to the vicilin superfamily, members of which play a variety of roles. The function of p16 may be related to the protection of chromatin structure against desiccation during seed development.

Amino Acid Sequence↗

Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds.

Outgrowth and patterning of the vertebrate limb are controlled by reciprocal interactions between the posterior mesenchyme (polarizing region) and a specialized ectodermal structure, the apical ectodermal ridge (AER). Sonic hedgehog (SHH) signalling by the polarizing region modulates fibroblast growth factor (FGF)4 signalling by the posterior AER, which in turn maintains the polarizing region (SHH/FGF4 feedback loop). Here we report that the secreted bone-morphogenetic-protein (BMP) antagonist Gremlin relays the SHH signal from the polarizing region to the AER. Mesenchymal Gremlin expression is lost in limb buds of mouse embryos homozygous for the limb deformity (Id) mutation, which disrupts establishment of the SHH/FGF4 feedback loop. Grafting Gremlin-expressing cells into ld mutant limb buds rescues Fgf4 expression and restores the SHH/FGF4 feedback loop. Analysis of Shh-null mutant embryos reveals that SHH signalling is required for maintenance of Gremlin and Formin (the gene disrupted by the ld mutations). In contrast, Formin, Gremlin and Fgf4 activation are independent of SHH signalling. This study uncovers the cascade by which the SHH signal is relayed from the posterior mesenchyme to the AER and establishes that Formin-dependent activation of the BMP antagonist Gremlin is sufficient to induce Fgf4 and establish the SHH/FGF4 feedback loop.

Animals↗

Interaction of mitogen-activated protein kinases with the kinase interaction motif of the tyrosine phosphatase PTP-SL provides substrate specificity and retains ERK2 in the cytoplasm.

ERK1 and ERK2 associate with the tyrosine phosphatase PTP-SL through a kinase interaction motif (KIM) located in the juxtamembrane region of PTP-SL. A glutathione S-transferase (GST)-PTP-SL fusion protein containing the KIM associated with ERK1 and ERK2 as well as with p38/HOG, but not with the related JNK1 kinase or with protein kinase A or C. Accordingly, ERK2 showed in vitro substrate specificity to phosphorylate GST-PTP-SL in comparison with GST-c-Jun. Furthermore, tyrosine dephosphorylation of ERK2 by the PTP-SLDeltaKIM mutant was impaired. The in vitro association of ERK1/2 with GST-PTP-SL was highly stable; however, low concentrations of nucleotides partially dissociated the ERK1/2.PTP-SL complex. Partial deletions of the KIM abrogated the association of PTP-SL with ERK1/2, indicating that KIM integrity is required for interaction. Amino acid substitution analysis revealed that Arg and Leu residues within the KIM are essential for the interaction and suggested a regulatory role for Ser(231). Finally, coexpression of PTP-SL and ERK2 in COS-7 cells resulted in the retention of ERK2 in the cytoplasm in a KIM-dependent manner. Our results demonstrate that the noncatalytic region of PTP-SL associates with mitogen-activated protein kinases with high affinity and specificity, providing a mechanism for substrate specificity, and suggest a role for PTP-SL in the regulation of mitogen-activated protein kinase translocation to the nucleus upon activation.

Amino Acid Sequence↗

Maximal strength and power characteristics in isometric and dynamic actions of the upper and lower extremities in middle-aged and older men.

Muscle cross-sectional area of the quadriceps femoris (CSAQF), maximal isometric strength (handgrip test and unilateral knee extension/flexion), the shape of isometric force-time curves, and power-load curves during concentric and stretch-shortening cycle (SSC) actions with loads ranging from 15 to 70% of one repetition maximum half-squat (1RMHS) and bench-press (1RMBP) were examined in 26 middle-aged men in the 40-year-old (M40) (mean age 42, range 35-46) and 21 elderly men in the 65-year-old age group (M65) (mean age 65, range 60-74). Maximal bilateral concentric (1RMHS and 1RMBP), unilateral knee extension (isometric; MIFKE and concentric; 1RMKE) strength and muscle CSA in M65 were lower (P < 0.001) than in M40. The individual values of the CSAQF correlated with the individual values of maximal concentric 1RMHS, 1RMKE and MIFKE in M65, while the corresponding correlations were lower in M40. The maximal MIFKE value per CSA of 4.54 +/- 0.7 N m cm-2 in M40 was greater (P < 0. 05-0.01) than that of 4.02 +/- 0.7 N m cm-2 recorded in M65. The maximal rate of force development of the knee extensors and flexors in M65 was lower (P < 0.01-0.001) and the heights in squat and counter-movement jumps as much as 27-29% lower (P < 0.001) than those recorded in M40. M65 showed lower (P < 0.001) concentric power values for both upper and lower extremity performances than those recorded for M40. Maximal power output was maximized at the 30-45% loads for the upper extremity and at the 60-70% loads for the lower extremity extensors in both age groups. Muscle activation of the antagonists was significantly higher (P < 0.01-0.001) during the isometric and dynamic knee extension actions in M65 than in M40. The present results support a general concept that parallel declines in muscle mass and maximal strength take place with increasing age, although loss of strength may vary in both lower and upper extremity muscles in relation to the type of action and that ageing may also lead to a decrease in voluntary neural drive to the muscles. Explosive strength and power seem to decrease with increasing age even more than maximal isometric strength in both actions but power was maximized at the 30-45% loads for the upper and at the 60-70% loads for the lower extremity action in both age groups. High antagonist muscle activity may limit the full movement efficiency depending on the type of muscle action, testing conditions and the velocity and/or the time duration of the action, especially in the elderly.

Adult↗

Gli3 (Xt) and formin (ld) participate in the positioning of the polarising region and control of posterior limb-bud identity.

During initiation of limb-bud outgrowth in vertebrate embryos, the polarising region (limb-bud organizer) is established upon activation of the Sonic Hedgehog (SHH) signaling molecule at the posterior limb-bud margin. Another hallmark of establishing anteroposterior limb-bud identities is the colinear activation of HoxD genes located at the 5' end of the cluster (5'HoxD genes). The unique and shared functions of Gli3 and formin in these determinative events were genetically analyzed using single and double homozygous Extra-toes (Xt; disrupting Gli3) and limb deformity (ld; disrupting formin) mouse embryos. Analysis of the limb skeletal phenotypes reveals genetic interaction of the two genes. In addition to loss of digit identity and varying degrees of polydactyly, proximal skeletal elements are severely shortened in Xt;ld double homozygous limbs. The underlying molecular defects affect both establishment of the polarising region and posterior limb-bud identity. In particular, the synergism between Gli3- and formin-mediated mesenchyme-AER interactions positions the SHH signaling center at the posterior limb-bud margin. The present study shows that establishment and positioning of the polarising region is regulated both by restriction of Shh through Gli3 and its positive feedback regulation through formin. Concurrently, Gli3 functions independently of formin during initial posterior nesting of 5'HoxD domains, whereas their subsequent distal restriction and anterior expansion depends on genetic interaction of Gli3 and formin.

Animals↗

PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction motif.

Protein kinases and phosphatases regulate the activity of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by controlling the phosphorylation of specific residues. We report the physical and functional association of ERK1/2 with the PTP-SL and STEP protein tyrosine phosphatases (PTPs). Upon binding, the N-terminal domains of PTP-SL and STEP were phosphorylated by ERK1/2, whereas these PTPs dephosphorylated the regulatory phosphotyrosine residues of ERK1/2 and inactivated them. A sequence of 16 amino acids in PTP-SL was identified as being critical for ERK1/2 binding and termed kinase interaction motif (KIM) (residues 224-239); it was shown to be required for phosphorylation of PTP-SL by ERK1/2 at Thr253. Co-expression of ERK2 with catalytically active PTP-SL in COS-7 cells impaired the EGF-induced activation of ERK2, whereas a PTP-SL mutant, lacking PTP activity, increased the ERK2 response to EGF. This effect was dependent on the presence of the KIM on PTP-SL. Furthermore, ERK1/2 activity was downregulated in 3T3 cells stably expressing PTP-SL. Our findings demonstrate the existence of a conserved ERK1/2 interaction motif within the cytosolic non-catalytic domains of PTP-SL and STEP, which is required for the regulation of ERK1/2 activity and for phosphorylation of the PTPs by these kinases. Our findings suggest that PTP-SL and STEP act as physiological regulators of the ERK1/2 signaling pathway.

3T3 Cells↗

[Ulcerative colitis and pregnancy].

BACKGROUND: The evolution of ulcerative colitis in pregnancy is far from clear. While some authors state that the disease aggravates during this period, others do not share this opinion. AIM: To assess the evolution of ulcerative colitis in pregnancy. PATIENTS AND METHODS: A paired case-control design was used in which 15 women, with diagnosed ulcerative colitis at the moment of becoming pregnant, were followed for 12 months and the activity of the disease was compared with that of the 12 months preceding the pregnancy. The activity of the disease in the period preceding the pregnancy was gathered retrospectively from the patient's charts. RESULTS: The mean age of the first ulcerative colitis crisis was 24 years. It was moderate in 49% and severe in 35% of women. During pregnancy 55% of women did not have a crisis, compared with 26.7% during the period preceding pregnancy (relative risk of not having a crisis during pregnancy of 1.7). During both periods, seven women had digestive complications, whereas extra digestive complications were not observed in 60% of patients during pregnancy and 11.8% of patients during the preceding period. Perinatal results were similar to those of the general population. CONCLUSIONS: In our group of patients the evolution of ulcerative colitis was better during pregnancy, reflected by a lower number of crisis.

Colitis, Ulcerative↗

[Enteral nutrition in severe ulcerative colitis. Digestive tolerance and nutritional efficiency].

BACKGROUNDS AND AIMS: Total parenteral nutrition (TPN) has been traditionally used as an adjunctive therapy in severe ulcerative colitis patients. We performed a prospective study to ascertain the safety, nutritional efficiency, tolerance and costs of total enteral nutrition in this situation. METHODS: After 48 hours of intensive medical treatment, severe ulcerative colitis patients initiated enteral feeding with a polymeric formula. The formula concentration and volume were increased daily. RESULTS: 17 patients (7 women, 10 men; age 36.8 +/- 12.8 years) with a mean clinical activity score of 15.6 +/- 1.5 were included. In 14 patients (82.4%) enteral nutrition was well tolerated, attaining in 11 of them more than 80% of the caloric requirements by day 4. In 3 cases we observed vomiting and bloating. Prealbumin levels improved significantly from 11.1 +/- 3.4 mg/dl to 22.7 +/- 6.8 mg/dl (p = 0.002) at the end of enteral nutrition (11.8 +/- 4.7 days). Albumin and other nutritional parameters did not change. CONCLUSIONS: Total enteral nutrition could be considered a safe and well tolerated nutritional support in these patients. Although albumin and other nutritional parameters did not change during the study period, the increase in prealbumin levels suggests a favourable anabolic effect of total enteral nutrition.

Adolescent↗

Neuropeptide Y Y1 receptors are involved in the vasoconstriction caused by human sympathetic nerve stimulation.

Neuropeptide Y, a novel neurotransmitter, interacts with selective membrane receptors to cause vasoconstriction. Frequency- and concentration-dependent isometric contractions were observed in human inferior mesenteric artery and vein mounted rings that were stimulated with either electrical pulses (70 V, 0.5 ms, 2.5-20 Hz) or noradrenaline. The antagonism elicited by 100 nM tetrodotoxin and 1 microM guanethidine confirmed the neuronal and sympathetic origins of the vasomotor response. Incubation with BIBP 3226 ((R)-N2-(di-phenacetyl)-N-(4-hydroxyphenyl)-methyl-D-arginineam ide), a selective neuropeptide Y Y1 receptor antagonist, significantly reduced the vasoconstriction. The incomplete antagonist activity of BIBP 3226 tends to support the hypothesis of sympathetic co-transmission involving neuropeptide Y, adenosine 5'-triphosphate and noradrenaline. These findings were confirmed in parallel studies using rat superior mesenteric artery and vein ring preparations.

Animals↗

Proinflammatory activity on rat carotid endothelium of albumins obtained by different procedures.

To investigate whether the proinflammatory activity of intravenously administered albumins is related to their preparation method, we compared bovine albumins obtained by alcohol precipitation and by heat shock. This last procedure produced a notable increase in monocyte adhesion/mm2 in rat carotid endothelium (48 +/- 31, n = 32 rats, vs 7 +/- 6, n = 24 rats, mean +/- S.D., P < 0.001). We found no changes in fluorescence emission in these two groups, and no correlation was observed between leukocyte adhesion and the contents of free fatty acids, free -SH groups, fructosamine, dimers and polymers. The inhibition profile of the proinflammatory activity by polyanionic molecules (fucoidan and dextran sulfate 500 kD) was compatible with the recognition of heat-shocked albumins by scavenger receptors. Thiol disulfide exchange in albumins was produced by ageing with cysteine and by incubation with protein disulfide isomerase. Albumins thus modified increased the adhesion of leukocytes to the endothelium, which indicates that some isomeric forms of albumin generated by thiol disulfide exchange may acquire proinflammatory behavior.

Alcohols↗

Reduced intestinal colonisation with F18-positive enterotoxigenic Escherichia coli in weaned pigs fed chicken egg antibody against the fimbriae.

Newly weaned pigs were fed a basal diet containing either egg antibody against fimbriae F18 at a high or low level, control egg powder or no egg, and challenged with enterotoxigenic Escherichia coli with fimbriae F18. The challenge was repeated after termination of the antibody treatment. Antibody-containing egg powder was produced by vaccination of hens with semi-purified fimbriae of the two variants F18ab and F18ac. Pigs eating egg powder with antibody against the same fimbrial variant were fully protected, even if the vaccine for the hens was produced with a different serotype devoid of enterotoxins. The effect was dose-dependent. The high dose of antibody against the heterologous variant of fimbriae F18 reduced colonisation at a level which was not significant. Ingestion of egg antibody partially suppressed the build-up of anti-colonisation immunity. Oral application of egg antibodies offers a promising approach for the prevention of infectious diseases of the digestive tract.

Animal Feed↗