Existence results for a damped second order abstract functional differential equation with impulses

In this work we study the existence and regularity of mild solutions for a damped second order abstract functional differential equation with impulses. The results are obtained using the cosine function theory and fixed point criterions. (C) 2009 Elsevier Ltd. All rights reserved.

Existence results for partial neutral functional differential equations with state-dependent delay

In this paper we study the existence of mild solutions for a class of first order abstract partial neutral differential equations with state-dependent delay. (C) 2008 Elsevier Ltd. All rights reserved.

Age and Method-dependent Variability of Predicted Oxygen Consumption in Congenital Heart Disease

Background and Purpose. There has been a lot of debate about the use of predicted oxygen consumption to calculate pulmonary vascular resistance using the Fick principle. We therefore comparatively analyzed predicted oxygen consumption in infants and children in specific age groups, using different methods (formulas), as an attempt to better understand the usefulness and limitations of predictions. Methods and Results. Four models (LaFarge & Miettinen, Bergstra et al., Lindahl, and Lundell et al.) were used to predict oxygen consumption in 200 acyanotic patients with congenital cardiac defects aged 0-2.0, > 2.0-4.0, > 4.0-6.0, and > 6.0-8.75 years (median 2.04 years). Significant differences were observed between the age groups (P < .001) and between the methods (P < .001), not related to diagnoses. Differences between methods were more impressive in the first age group (P < .01). In patients aged 0-2.0 years, the lowest values of oxygen consumption (corresponding to the highest estimates of pulmonary vascular resistance) were obtained with the method of Lindahl; above this age, any method except that of Lundell et al. Conclusions. Although measuring oxygen consumption is always preferable, a rational use of predictions, using different methods, may be of help in situations where measurements are definitely not possible.

Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing`s syndrome patients

Objective: GH secretagogues (GHS) produce exaggerated ACTH and cortisol responses in Cushing`s disease (CD) patients, attributable to their direct action on GH-releasing peptide receptor type la (GHSR-1a). However, there are no studies correlating the ill vivo response to GHS and GHSR-1a mRNA expression in ACTH-dependent Cushing`s syndrome (CS) patients. The aim of this study is to correlate the patterns of ACTH and cortisol response to GH-releasing peptide-6 (GHRP-6) to GHSR-1a expression in ACTH-dependent CS patients Design: Prospective study in a tertiary referral hospital center. Fifteen CD patients and two ectopic ACTH syndrome (EAS) patients were studied. Methods: Tumor fragments were submitted to RNA extraction, and GHSR-1a expression was studied through real-time qPCR and compared with normal tissue samples. The patients were also submitted to desmopressin test and vasopressin receptor type 1B (AVPR1B) mRNA analysis by qPCR. Results: GHSR-1a expression was similar in normal pituitary samples and in corticotrophic tumor samples. GHSR-1a expression was higher in patients (CD and EAS) presenting ill vivo response to GHRP-6. Higher expression of AVPR1B was observed in the EAS patients responsive to desmopressin, as well as in corticotrophic tumors, as compared with normal pituitary samples, but no correlation between AVPR1B expression and response to desmopressin was observed in the CD patients. Conclusions: Our results revealed a higher expression of GHSR-1a in the ACTH-dependent CS patients responsive to GHRP-6, suggesting an association between receptor gene expression and ill vivo response to the secretagogue in both the CD and the EAS patients.

Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.

Gut ischemia/reperfusion induced acute lung injury is an alveolar macrophage dependent event

Background:. Although the role of the lung alveolar macrophage (AM) as a mediator of acute lung injury (ALI) after lung ischemia/reperfusion (I/R) has been suggested by animal experiments, it has not been determined whether AMs mediate ALI after intestinal I/R. The objective of this study was to determine the effect of AM elimination on ALI after intestinal I/R in rats. Mwthods: Male Wistar rats (n = 90) were randomly divided into three groups: the clodronate-liposomes (CLOD-LIP) group received intratracheal treatment with CLOD-LIP; the liposomes (LIP) group received intratracheal treatment with LIP; and the nontreated (UNTREAT) group received no treatment. Twenty-four hours later each group was randomly divided into three subgroups: the intestinal I/R subgroup was subjected to 45-minute intestinal ischemia and 2-hour reperfusion; the laparotomy (LAP) subgroup was subjected to LAP and sham procedures; the control (CTR) subgroup received no treatment. At the end of reperfusion, ALI was quantitated in all the animals by the Evans blue dye (EBD) method. Results: ALI values are expressed as EBD lung leakage (mu g EBD/g dry lung weight). EBD lung leakage values in the CLOD-LIP group were 32.59 +/- 12.74 for I/R, 27.74 +/- 7.99 for LAP, and 33.52 +/- 10.17 for CTR. In the LIP group, lung leakage values were 58.02 +/- 18.04 for I/R, 31.90 +/- 8.72 for LAP, and 27.17 +/- 11.48 for CTR. In the UNTREAT group, lung leakage values were 55.60 +/- 10.96 for I/R, 35.99 +/- 6.89 for LAP, and 30.83 +/- 8.41 for CTR. Within each group, LAP values did not differ from CTR values. However, in the LIP and UNTREAT groups, values for both the LAP and CTR subgroups were lower than values for the I/R subgroup (p < 0.001). The CLOD-LIP I/R subgroup value was less (p < 0.001) than the I/R subgroup values in the LIP and UNTREAT groups. These results indicated that I/R provokes ALI that can be prevented by CLOD-LIP treatment, and further suggested that AMs are essential for ALI occurrence induced by intestinal I/R in rats.

Protein disulfide isomerase redox-dependent association with p47(phox): evidence for an organizer role in leukocyte NADPH oxidase activation

Mechanisms of leukocyte NADPH oxidase regulation remain actively investigated. We showed previously that vascular and macrophage oxidase complexes are regulated by the associated redox chaperone PDI. Here, we investigated the occurrence and possible underlying mechanisms of PDI-mediated regulation of neutrophil NADPH oxidase. In a semirecombinant cell-free system, PDI inhibitors scrRNase (100 mu g/mL) or bacitracin (1 mM) near totally suppressed superoxide generation. Exogenously incubated, oxidized PDI increased (by similar to 40%), whereas PDIred diminished (by similar to 60%) superoxide generation. No change occurred after incubation with PDI serine-mutated in all four redox cysteines. Moreover, a mimetic CxxC PDI inhibited superoxide production by similar to 70%. Thus, oxidized PDI supports, whereas reduced PDI down-regulates, intrinsic membrane NADPH oxidase complex activity. In whole neutrophils, immunoprecipitation and colocalization experiments demonstrated PDI association with membrane complex subunits and prominent thiol-mediated interaction with p47(phox) in the cytosol fraction. Upon PMA stimulation, PDI was mobilized from azurophilic granules to cytosol but did not further accumulate in membranes, contrarily to p47(phox). PDI-p47(phox) association in cytosol increased concomitantly to opposite redox switches of both proteins; there was marked reductive shift of cytosol PDI and maintainance of predominantly oxidized PDI in the membrane. Pulldown assays further indicated predominant association between PDIred and p47(phox) in cytosol. Incubation of purified PDI (> 80% reduced) and p47(phox) in vitro promoted their arachidonate-dependent association. Such PDI behavior is consistent with a novel cytosolic regulatory loop for oxidase complex (re) cycling. Altogether, PDI seems to exhibit a supportive effect on NADPH oxidase activity by acting as a redox-dependent enzyme complex organizer. J. Leukoc. Biol. 90: 799-810; 2011.

Family advocacy roles and highly dependent residents in nursing homes

A developing critique has questioned the practical utility of user rights policy initiatives for highly dependent residents of nursing homes. This paper seeks to extend this critique to the advocacy roles that families have been accorded within the policy initiatives, The discussion is based on a qualitative research study of family participation in six aged care units, The paper argues that the capacity of families to act as advocates for highly dependent nursing home residents is is limited by the their weak position within the organisations and the complexity of their relations with staff It questions both the applicability and the appropriateness of rights models which do not take sufficient account of the structure and meaning of care.

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.

Antimalarial Treatment May Have a Time-Dependent Effect on Lupus Survival

Objective. To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. Methods. Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). Results. Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P < 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). Conclusion. Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

Age-dependent increase in blood pressure in two different Native American communities in Brazil

Objective Cardiovascular risk factors were surveyed in two Indian populations (Guarani, n=60; Tupinikin, n=496) and in a non-Indian group (n=114) living in the same reserve in southeast Brazilian coast. The relationship between an age-dependent blood pressure (BP) increase with salt consumption was also investigated. Methods Overnight (12 h) urine was collected to evaluate Na excretion. Fasting glucose and lipids, anthropometry, BP, ECG and carotid-femoral pulse wave velocity (PWV) were measured in a clinic visit. Participation (318 men/352 women, age 20-94 years; mean=37.6 +/- 14.9 years) comprised 80% of the eligible population. Results The prevalence of hypertension, diabetes and high cholesterol was similar in Tupinikins and in non-Indians and higher than in Guaranis. The prevalence of smoking and obesity was higher in the latter group. Hypertension and diabetes were detected in only one individual of the Guarani group. Mean BP adjusted to age and BMI was significantly lower (P<0.01) in Guaranis (82.8 +/- 1.6 mmHg) than in Tupinikins (92.3 +/- 0.5 mmHg) and non-Indians (91.6 +/- 1.1 mmHg). Urinary Na excretion (mEq/12h), however, was similar in the three groups (Guarani=94 +/- 40; Tupinikin=105 +/- 56; non-Indian=109 +/- 55; P>0.05). PWV (m/s) was lower (P<0.01) in Guarani (7.5 +/- 1.4) than in Tupinikins (8.8 +/- 2.2) and non-Indians (8.4 +/- 2.0). Multiple regression analysis showed that age and waist-to-hip ratio (WHR) were independent predictors of SBP and DBP (r(2)=0.44) in Tupinikins, whereas the WHR was the unique independent predictor of BP variability in Guaranis (r(2)=0.22). Conclusion Lower BP levels in Guaranis cannot be explained by low salt intake observed in other primitive populations. J Hypertens 27:1753-1760 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Extracellular calcium stimulates Na+-dependent putrescine uptake in B16 melanoma cells

The regulation of putrescine transport in difluoromethylornithine-treated B16 melanoma cells by extracellular Ca2+ has been investigated. It was found that physiological concentrations of Ca2+ were essential for optimum uptake of putrescine and spermidine. Mg2+, albeit at higher concentrations, also could potentiate polyamine transport. The maximum rate of putrescine uptake increased from 1698 +/-: 67 pmol/min/mg DNA in the absence of Ca2+ to 3100 +/- 98 pmol/min/mg DNA in the presence of 0.5 mM Ca2+. There was no change in K-m. While Ca2+ enhanced transport of both putrescine and spermidine it did not affect the uptake of deoxyglucose, thymidine or leucine. Putrescine did not alter Ca2+ fluxes suggesting that the two cations do not share a common transport system. The effects of Ca2+ on putrescine uptake appeared to be mediated extracellularly firstly because Ca2+ did not potentiate putrescine uptake in the presence of A23187 and secondly, because the effects of Ca2+ were completely inhibited by the lanthanide Tb3+, which binds to calcium-dependent proteins and does not readily cross biological membranes. Ca2+ did not affect putrescine transport in the absence of extracellular Na+. Moreover, the rate of putrescine uptake in the absence of Ca2+ was similar to that in the absence of extracellular Na+. The results from this study indicate that polyamine transport is stimulated by extracellular Ca2+ and suggest that Ca2+ is required for activity of the Na+-dependent transporter only. This transporter appears to possess a regulatory binding site for divalent cations. (C) 1997 Elsevier Science Ltd.

Increased tissue resistance in the nude mouse against Candida albicans without altering strain-dependent differences in susceptibility

Strain differences in tissue responses to infection with Candida albicans were examined in nude mice having susceptible (CBA/CaH) and resistant (BALB/c) parentage. Homozygous (nu/nu) mice of both strains were more resistant to systemic infection with C. albicans than heterozygous (nu/+) littermates as indicated by a reduction in both the severity of tissue damage and colony counts in the brain and kidney. However, the tissue lesions in nu/nu CBA/CaH mice were markedly more severe than those in nu/nu mice with the BALB/c background. This pattern was reflected in the greater fungal burden in the CBA/CaH strain. Analysis of cDNA from infected tissues using a competitive polymerase chain reaction excluded interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) as mediators of the enhanced resistance of the nude mice. The results confirm that the different patterns of lesion severity in BALB/c and CBA/CaH mice do not involve T lymphocyte-mediated pathology, and are consistent with the hypothesis that strain-dependent tissue damage is not dependent on the effector function of macrophages or their precursors.