Host-microorganism interactions in lung diseases.

Until recently, the airways were thought to be sterile unless infected; however, a shift towards molecular methods for the quantification and sequencing of bacterial DNA has revealed that the airways harbour a unique steady-state microbiota. This paradigm shift is changing the way that respiratory research is approached, with a clear need now to consider the effects of host-microorganism interactions in both healthy and diseased lungs. We propose that akin to recent discoveries in intestinal research, dysbiosis of the airway microbiota could underlie susceptibility to, and progression and chronicity of lung disease. In this Opinion article, we summarize current knowledge of the airway microbiota and outline how host-microorganism interactions in the lungs and other tissues might influence respiratory health and disease.

Accurate performance of a rat model of schizophrenia in the water maze depends on visual cue availability and stability: a distortion in cognitive mapping abilities?

Rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) in an animal model of schizophrenia based on transient glutathione deficit. The BSO treated rats were impaired in patrolling a maze or a homing table when adult, yet demonstrated preserved escape learning, place discrimination and reversal in a water maze task [37]. In the present work, BSO rats' performance in the water maze was assessed in conditions controlling for the available visual cues. First, in a completely curtained environment with two salient controlled cues, BSO rats showed little accuracy compared to control rats. Secondly, pre-trained BSO rats were impaired in reaching the familiar spatial position when curtains partially occluded different portions of the room environment in successive sessions. The apparently preserved place learning in a classical water maze task thus appears to require the stability and the richness of visual landmarks from the surrounding environment. In other words, the accuracy of BSO rats in place and reversal learning is impaired in a minimal cue condition or when the visual panorama changes between trials. However, if the panorama remains rich and stable between trials, BSO rats are equally efficient in reaching a familiar position or in learning a new one. This suggests that the BSO accurate performance in the water maze does not satisfy all the criteria for a cognitive map based navigation on the integration of polymodal cues. It supports the general hypothesis of a binding deficit in BSO rats.

Marriage as a Rat Race: Noisy Pre-Marital Investments with Assortative Matching

We study the incentive to invest to improve marriage prospects, in a frictionless marriage market with non-transferable utility. Stochastic returns to investment eliminate the multiplicity of equilibria in models with deterministic returns, and a unique equilibrium exists under reasonable conditions. Equilibrium investment is efficient when the sexes are symmetric. However, when there is any asymmetry, including an unbalanced sex ratio, investments are generically excessive. For example, if there is an excess of boys, then there is parental over-investment in boys and under-investment in girls, and total investment will be excessive.

Donor's and organ representations in liver, kidney, heart and lung transplantation : a qualitative longitudinal study

Purpose: Organ transplantation is a biological and psychological challenge and graft acceptance is an important achievement for patients. Patients' concerns toward the deceased donor and the organ may contribute to this process. Method: Forty-seven patients involved in heart (N=9), liver (N=8), lung (N=14) and kidney (N=16) transplantation participated in IRB-approved longitudinal semi-structured interviews: (T1) registered on the waiting-list, (T2) six months and (T3) twelve months after transplantation. Qualitative pattern analysis (QUAPA) was carried out on the verbatim transcripts and concerns about the donor and the organ were then analysed. Results: - Donor's representation: At T1, patients were reluctant to talk about the donor: 27% expressed culpability and 19% accepted the clause of anonymity. At T2, intense emotions were associated with the reminiscing about the donor and 45% highlighted the generosity of his/her act. In addition, heart, lung and kidney recipients were concerned about the donor's identity: 42% challenged the clause of anonymity. Liver recipients complained about anonymity, but could nevertheless cope with it. At T3, 47% of heart, lung and kidney recipients thought daily of the donor and 33% were still looking for information about him/her. Liver recipients rarely have thoughts about the donor. - Organ representation: At T1, organ descriptions were biomedical (49% of the interviewees) and more rarely, mainly heart candidates, referred to the symbolic meaning of the organ. After transplantation (T2-T3), function was underlined. Acceptance and organ integration were associated with post-operative outcomes (23%) and psychological well-being (45%). Some patients (32%) inferred the donor's personality from the organ quality and felt privileged having received an organ in such a good state. Conclusion: Donor's representations should be explored during the transplantation process as they play an important role in the psychological acceptance of the graft.

Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

Pharmacological and toxicological evaluation of Alpinia speciosa

Alpinia speciosa Schum or A. nutans is a plant of the Zingiberanceae family, Known popularly as "colony" (colônia) and used as a diuretic and to control hypertensión. We have determinated the concentration of Na+ and K+ found in the alcoholic extract and in the tea concoction. They contained 51.0mEq Na+, and 132 mEq K+ in the extract, and 0,0 mEq of Na+ and 26 mEq K+ in the tea. Phytochemical analysis of the leaves demonstrated the presence of catecquic tanins, phenols and alkaloids, and also some essential oils. When injected intra-peritoneally the hydroalcoholic extract, in range of 100 a 1400 mg/Kg, (or 2500-18000 mg/Kg orally) produced in mice: writhing, psychomorot excitation, hypokinesis and pruritus. The LD50 by ip was 0.760 + or - 0.126 g/Kg and 10.0 + or - 2.5 g/Kg by oral administration for the hydroalcoholic extract. Subacute toxicity made injecting daily for 30 days the LD10 in rats caused an increase in transaminases and lactate dehydrogenase, whereas other parameters such as nlood glucose, urea and creatinine were normal. A histopathological analysis of liver, spleen, gut, lung and heart showed no alterations. The drug also produced a prolongation of the sleeping time. The hydroalcoholic extract induced int he rat and in the dog a dose-dependent fall in blood pressure in doses of 10 to 30 mg/Kg. In isolated atria the extract induced a reduction of the frequnecy and in the inotropic responses. Neither the extract nor the tea had an effect on the diuresis of the rat.

Enterolobin induces rat paw oedema independently of PAF-acether

The potential participation of PAF-acether (PAF) on the paw oedema triggered by enterolobin was investigated. Intraplantar injections of enterolobin )5-20 µg/paw) yielded a dose response curve for edema which appeared after 30 min, peaked in the interval between 2-4 h and faded after 24h. The pre-treatment with BN 52021, but not with other PAF antagonists such as PCA 4248 or WEB 2086, significantly blocked enterolobin-induced oedema. To clarify better the discrepant results obtained with the PAF antagonists, desensitization to PAF was performed. The oedema triggered by enterolobin was not modified in paf desensitized animals. It was concluded that the paw inflammation induced by enterolobin does not require PAF mechanism.

Differentiation of rat striatal embryonic stem cells in vitro: monolayer culture vs. three-dimensional coculture with differentiated brain cells.

Several groups have demonstrated the existence of self-renewing stem cells in embryonic and adult mouse brain. In vitro, these cells proliferate in response to epidermal growth factor, forming clusters of nestin-positive cells that may be dissociated and subcultured repetitively. Here we show that, in stem cell clusters derived from rat embryonic striatum, cell proliferation decreased with increasing number of passages and in response to elevated concentrations of potassium (30 mM KCl). In monolayer culture, the appearance of microtubule-associated protein type-5-immunoreactive (MAP-5(+)) cells (presumptive neurons) in response to basic fibroblast growth factor (bFGF) was reduced at low cell density and with increasing number of passages. In the presence of bFGF, elevated potassium caused a more differentiated neuronal phenotype, characterized by an increased proportion of MAP-5(+) cells, extensive neuritic branching, and higher specific activity of glutamic acid decarboxylase. Dissociated stem cells were able to invade cultured brain cell aggregates containing different proportions of neurons and glial cells, whereas they required the presence of a considerable proportion of glial cells in the host cultures to become neurofilament H-positive. The latter observation supports the view that astrocyte-derived factors influence early differentiation of the neuronal cell lineage.

Family physician involvement in cancer care and lung cancer patient emotional distress and quality of life.

PURPOSE: This study aims to describe emotional distress and quality of life (QoL) of patients at different phases of their lung cancer and the association with their family physician (FP) involvement. METHODS: A prospective study on patients with lung cancer was conducted in three regions of Quebec, Canada. Patients completed, at baseline, several validated questionnaires regarding their psychosocial characteristics and their perceived level of FP involvement. Emotional distress [profile of mood states (POMS)] and QoL [European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30)] were reassessed every 3-6 months, whether patients had metastasis or not, up to 18 months. Results were regrouped according to cancer phase. Mixed models with repeated measurements were performed to identify variation in distress and QoL. RESULTS: In this cohort of 395 patients, distress was low at diagnosis (0.79 ± 0.7 on a 0-4 scale), raising to 1.36 ± 0.8 at the advance phase (p < 0.0001). Patient's global QoL scores significantly decreased from the diagnosis to the advance phase (from 66 to 45 on a 0-100 scale; p < 0.0001). At all phases of cancer, FP involvement was significantly associated with patients' distress (p = 0.0004) and their global perception of QoL (p = 0.0080). These associations remained statistically significant even after controlling for age, gender, and presence of metastases. CONCLUSIONS: This study provides new knowledge on patients' emotional distress and QoL with cancer evolution and, particularly, their association with FP involvement. Other studies should be conducted to further explore FP role in cancer supportive care.

Nicotine-induced release of vasopressin in the conscious rat: role of opioid peptides and hemodynamic effects.

Nicotine has been shown to stimulate the release of vasopressin and to cause significant hemodynamic changes. The mechanisms leading to enhanced vasopressin secretion and the vascular consequences of the high plasma vasopressin levels during nicotine infusion have not yet been determined. Therefore, the purposes of the present study were 1) to examine in normal conscious rats the role of opioid peptides in the nicotine-induced increase in plasma vasopressin levels and 2) to assess the role of vasopressin in the hemodynamic effects of nicotine (20 micrograms/min for 15 min) using a specific V1 antagonist of the vascular actions of vasopressin. Plasma vasopressin levels were significantly increased in the nicotine-treated animals (39.5 +/- 10 vs. 3.7 +/- 0.6 pg/ml in the controls, P less than .01). Pretreatment with naloxone, an antagonist of opioids at their receptors, did not reduce the vasopressin levels (47.7 +/- 9 pg/ml). Nicotine also increased mean blood pressure (122.5 +/- 2.5 to 145.2 +/- 3.3 mm Hg, P less than .01) and decreased heart rate (461 +/- 6 to 386 +/- 14.5 beats/min, P less than .05). Administration of the vasopressin V1 antagonist before the nicotine infusion did not affect the systemic hemodynamics or the regional blood flow distribution, as assessed by radiolabeled microspheres. Thus, these results suggest that the nicotine-induced secretion of vasopressin is not mediated by opioid receptors and that the high plasma vasopressin levels do not exert any significant hemodynamic effect on cardiac output or blood flow distribution.

Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that can be activated by various xenobiotics and natural fatty acids. These transcription factors primarily regulate genes involved in lipid metabolism and also play a role in adipocyte differentiation. We present the expression patterns of the PPAR subtypes in the adult rat, determined by in situ hybridization using specific probes for PPAR-alpha, -beta and -gamma, and by immunohistochemistry using a polyclonal antibody that recognizes the three rat PPAR subtypes. In numerous cell types from either ectodermal, mesodermal, or endodermal origin, PPARs are coexpressed, with relative levels varying between them from one cell type to the other. PPAR-alpha is highly expressed in hepatocytes, cardiomyocytes, enterocytes, and the proximal tubule cells of kidney. PPAR-beta is expressed ubiquitously and often at higher levels than PPAR-alpha and -gamma. PPAR-gamma is expressed predominantly in adipose tissue and the immune system. Our results suggest new potential directions to investigate the functions of the different PPAR subtypes.