The lived experience of adults with heart failure: a phenomenological study.

BACKGROUND: Although a number of studies have been conducted on patients with Heart Failure (HF), they have not given a rigorous comprehensive description of what it is like to live with HF. The objective of this study was to describe the lived experience of adults with HF. STUDY DESIGN: A hermeneutic phenomenological design was used. METHODS: Cohen's method was used to conduct the study. Thirty HF patients were enrolled between February and July 2014 from an outpatient cardiovascular clinic in Tuscany, Italy. Phenomenological interviews took place at patients' homes, and the investigators analyzed verbatim transcripts. Once data saturation was achieved, to ensure data trustworthiness, participants were asked to confirm all the extracted themes. Atals.ti vers.7 was used for data analysis. RESULTS: The patients were mostly male (67%) with a mean age of 71 (SD 9.15) and an age range of 48-86. Seven themes emerged from the phenomenological analysis: 1) important life changes; 2) social isolation caused by the illness; 3) anger and resignation associated with the disease; 4) relief from spirituality; 5) will to live; 6) uncertainty about the future and 7) the inescapability of disease and death. CONCLUSIONS: The meaning that patients attribute to their lived experience helps to create their needs, which are important to direct care. Family support and religious beliefs are an important source for HF patients to better manage their fears and cope with the future. Findings of this study provide nurses with a comprehensive description of what it is like to live with HF, which can be useful in helping to meet patients' needs more effectively and in tailoring interventions.

Full mouth periodontal debridement with or without adjunctive metronidazole gel in smoking patients with chronic periodontitis: A pilot study.

BACKGROUND AND OBJECTIVE: The evidence of effectiveness of metronidazole (Mtz) as an adjunct therapy to periodontal procedure in the treatment of patients with chronic periodontitis is not conclusive. The aim of this study was to compare the effect of Mtz (delivered locally as a gel or systemically as a tablet) as an adjunctive therapy with full mouth periodontal debridement (1 h of ultrasonic calculus/plaque removal) in smokers with chronic periodontitis. MATERIAL AND METHODS: This pilot study involved 30 smokers with at least six teeth with a clinical attachment loss of ≥ 5 mm and probing pocket depth (PPD) of ≥ 5 mm. They were randomly assigned into one of three groups (n = 10): (i) 3 g daily of placebo gel applied topically (using a dental tray with the gel overnight) + periodontal debridement; (ii) 3 g daily of a 15% Mtz benzoate gel applied topically (using a dental tray with the gel overnight) + periodontal debridement; and (iii) a daily single dose of 750 mg Mtz (Flagyl(®)) + periodontal debridement. Clinical parameters (visible plaque index, gingival bleeding index [GBI], relative attachment level and PPD) and quantitative analysis (by real-time polymerase chain reaction) of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia were assessed at baseline and at 1, 3 and 6 mo after periodontal debridement. RESULTS: There was no statistically significant difference in the average GBI and visible plaque index values at baseline between the groups (p ≥ 0.05). There was no significant difference between groups in all parameters evaluated (p ≥ 0.05). Significant reductions in GBI at 3 and 6 mo were observed in all groups (p < 0.05). Significant reductions in both PPD and relative attachment level at 1, 3 and 6 mo were observed in all groups (p < 0.05). Significant reductions in bacterial levels at 7 and 30 d were observed in all groups (p < 0.05). CONCLUSION: Adjunctive use of Mtz (gel or tablet) to periodontal debridement had similar clinical and microbiological improvement compared to treatment with placebo + periodontal debridement in smokers with chronic periodontitis up to 6 mo post-treatment. Further studies are necessary to confirm the clinical relevance of these findings.

Effect of particles of ashes produced from sugarcane burning on the respiratory system of rats.

The practice of burning sugarcane obtained by non-mechanized harvesting exposes workers and the people of neighboring towns to high concentrations of particulate matter (PM) that is harmful to health, and may trigger a series of cardiorespiratory diseases. The aim of this study was to analyze the chemical composition of the micro-particles coming from sugarcane burning residues and to verify the effects of this micro-particulate matter on lung and tracheal tissues. Micro-particulate matter (PM10) was obtained by dissolving filter paper containing burnt residues in NaCl solution. This material was instilled into the Wistar rats' nostrils. Histological analyses (hematoxylin and eosin - HE) of cardiac, lung and tracheal tissues were performed. Inflammatory mediators were measured in lung tissues by using ELISA. The chemical composition of the particulate material revealed a large quantity of the phthalic acid ester, high concentrations of phenolic compounds, anthracene and polycyclic aromatic hydrocarbons (PAH). Histological analysis showed a reduction in subjacent conjunctive tissue in the trachea, lung inflammation with inflammatory infiltrate formation and reduction of alveolar spaces and a significant increase (p<0.05) in the release of IL-1α, IL-1ß, IL-6, and INF-γ in the group treated with PM10 when compared to the control group. We concluded that the burning sugarcane residues release many particles, which have toxic chemical compounds. The micro-particulate matter can induce alterations in the respiratory system.

Proteomic analysis of Porphyromonas gingivalis exposed to nicotine and cotinine.

BACKGROUND AND OBJECTIVE: Smokers are more predisposed than nonsmokers to infection with Porphyromonas gingivalis, one of the most important pathogens involved in the onset and development of periodontitis. It has also been observed that tobacco, and tobacco derivatives such as nicotine and cotinine, can induce modifications to P. gingivalis virulence. However, the effect of the major compounds derived from cigarettes on expression of protein by P. gingivalis is poorly understood. Therefore, this study aimed to evaluate and compare the effects of nicotine and cotinine on the P. gingivalis proteomic profile. MATERIAL AND METHODS: Total proteins of P. gingivalis exposed to nicotine and cotinine were extracted and separated by two-dimensional electrophoresis. Proteins differentially expressed were successfully identified through liquid chromatography-mass spectrometry and primary sequence databases using MASCOT search engine, and gene ontology was carried out using DAVID tools. RESULTS: Of the approximately 410 protein spots that were reproducibly detected on each gel, 23 were differentially expressed in at least one of the treatments. A particular increase was seen in proteins involved in metabolism, virulence and acquisition of peptides, protein synthesis and folding, transcription and oxidative stress. Few proteins showed significant decreases in expression; those that did are involved in cell envelope biosynthesis and proteolysis and also in metabolism. CONCLUSION: Our results characterized the changes in the proteome of P. gingivalis following exposure to nicotine and cotinine, suggesting that these substances may modulate, with minor changes, protein expression. The present study is, in part, a step toward understanding the potential smoke-pathogen interaction that may occur in smokers with periodontitis.

Bronchodilator and anti-inflammatory activities of glaucine: In vitro studies in human airway smooth muscle and polymorphonuclear leukocytes.

1. Selective phosphodiesterase 4 (PDE4) inhibitors are of potential interest in the treatment of asthma. We examined the effects of the alkaloid S-(+)-glaucine, a PDE4 inhibitor, on human isolated bronchus and granulocyte function. 2. Glaucine selectively inhibited PDE4 from human bronchus and polymorphonuclear leukocytes (PMN) in a non-competitive manner (Ki=3.4 microM). Glaucine displaced [3H]-rolipram from its high-affinity binding sites in rat brain cortex membranes (IC50 approximately 100 microM). 3. Glaucine inhibited the spontaneous and histamine-induced tone in human isolated bronchus (pD2 approximately 4.5). Glaucine (10 microM) did not potentiate the isoprenaline-induced relaxation but augmented cyclic AMP accumulation by isoprenaline. The glaucine-induced relaxation was resistant to H-89, a protein kinase A inhibitor. Glaucine depressed the contractile responses to Ca2+ (pD'2 approximately 3.62) and reduced the sustained rise of [Ca2+]i produced by histamine in cultured human airway smooth muscle cells (-log IC50 approximately 4.3). 4. Glaucine augmented cyclic AMP levels in human polymorphonuclear leukocytes challenged with N-formyl-Met-Leu-Phe (FMLP) or isoprenaline, and inhibited FMLP-induced superoxide generation, elastase release, leukotriene B4 production, [Ca2+]i signal and platelet aggregation as well as opsonized zymosan-, phorbol myristate acetate-, and A23187-induced superoxide release. The inhibitory effect of glaucine on superoxide generation by FMLP was reduced by H-89. 5. In conclusion, Ca2+ channel antagonism by glaucine appears mainly responsible for the relaxant effect of glaucine in human isolated bronchus while PDE4 inhibition contributes to the inhibitory effects of glaucine in human granulocytes. The very low PDE4/binding site ratio found for glaucine makes this compound attractive for further structure-activity studies.

Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study.

We have investigated the role of human bronchial cyclic nucleotide phosphodiesterases in the effects of fenspiride, a drug endowed with bronchodilator and anti-inflammatory properties. Functional studies on human isolated bronchi showed that fenspiride (10(-6)-3 x 10(-3) M, 30 min) induced a shift to the left of the concentration-response curves for isoprenaline and sodium nitroprusside with -logEC50 values of 4.1+/-0.1 (n = 7) and 3.5+/-0.2 (n = 8), respectively. Biochemical studies were carried out on three human bronchi in which separation of cyclic nucleotide phosphodiesterase isoenzymes was performed by ion exchange chromatography followed by determination of phosphodiesterase activity with a radioisotopic method. Phosphodiesterase 4 (cyclic AMP-specific) and phosphodiesterase 5 (cyclic GMP-specific) were the major phosphodiesterase isoforms present in the human bronchial tissue. The presence of phosphodiesterase 1 (Ca2+/calmodulin-stimulated), phosphodiesterase 2 (cyclic GMP-stimulated) and, in two cases, phosphodiesterase 3 (cyclic GMP-inhibited) was also identified. Fenspiride inhibited phosphodiesterase 4 and phosphodiesterase 3 activities with -logIC50 values of 4.16+/-0.09 and 3.44+/-0.12, respectively. Phosphodiesterase 5 activity was also inhibited with a -logIC50 value of approximately 3.8. Fenspiride (< or = 10(-3) M) produced less than 25% inhibition of phosphodiesterase 1 and phosphodiesterase 2 activities. In conclusion, fenspiride is an effective inhibitor of both cyclic AMP and cyclic GMP hydrolytic activity in human bronchial tissues and this action may contribute to its airway effects.

Effects of erythromycin on chemoattractant-activated human polymorphonuclear leukocytes.

1. Erythromycin (2-100 micrograms ml-1) produced a concentration-related inhibition of superoxide generation and elastase release induced by in vitro exposure of human polymorphonuclear leukocytes (PMNs) to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP; 30 nM). 2. By contrast, erythromycin (100 micrograms ml-1) did not alter the leukotriene B4 production elicited by FMLP (30 nM; in the presence of thimerosal 20 microM) or the intracellular calcium changes promoted by FMLP (30 nM; in the absence or presence of thimerosal 20 microM). 3. These results indicate that by reducing chemoattractant-triggered release of oxidative and proteolytic mediators from human PMNs, erythromycin may have clinically useful antiinflammatory effects.

Pharmacological activity of PF-904 in guinea pig in vivo, and on human bronchus and neutrophils in vitro.

The effects of PF-904 (4-amino-1-ethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide), a pyrazinothiadiazine derivative, were examined in guinea-pig airways in vivo, in human isolated bronchus and human polymorphonuclear leukocytes. PF-904 (12.5-200 mg/kg, intraduodenal) reduced bronchoconstriction in response to histamine, arachidonic acid, platelet-activating factor (PAF) and methacholine. PF-904 (50-200 mg/kg) prevented PAF-induced airways hyperreactivity and inhibited antigen-induced bronchoconstriction, airway microvascular leakage and eosinophil lung accumulation, but antigen-induced airways hyperresponsiveness was not reduced. PF-904 (1 microM-1 mM) produced complete inhibition of spontaneous (-logEC50 = 3.57+/-0.04; n = 10) and histamine-stimulated tone (-logEC50 = 3.66+/-0.07; n = 10) of human isolated bronchus. Glibenclamide (10 microM) or precontraction with KCl (80 mM) did not impede PF-904-induced bronchial relaxation. PF-904 inhibited cyclic AMP (-logIC50 = 2.83+/-0.25; n = 8) and cyclic GMP (-logIC50 = 2.90+/-0.21; n = 8) phosphodiesterase activity in human bronchus. The activity of type IV phosphodiesterase was inhibited by PF-904 (-logIC50 = 3.43+/-0.11; n= 3). PF-904 also inhibited superoxide release by N-formylmethionyl-leucyl-phenylalanine-stimulated human polymorphonuclear leukocytes, but the maximal effect was approx. 50% of that produced by rolipram (10 microM). This profile of activities of PF-904 suggests that this compound has potential therapeutic value as an anti-asthma drug.

Inhibitory effects of N-acetylcysteine on superoxide anion generation in human polymorphonuclear leukocytes.

It has been suggested that reactive oxygen species released by activated polymorphonuclear leukocytes (PMN) in man is one mechanism of tissue injury. Therapeutic action aimed at increasing antioxidant defence mechanisms is still a clinical challenge. This study examines the activity of N-acetylcysteine, a known antioxidant, in the protection of PMN exposed in-vitro to the chemoattractant peptide fMet-Leu-Phe (FMLP), the protein kinase C activator phorbol myristate acetate or the lipid peroxidation promoter t-butyl hydroperoxide. FMLP (3-300 nM) and phorbol myristate acetate (160 pm-160 nM) induced concentration-related superoxide anion generation. Pre-treatment with N-acetylcysteine (33-333 microM) resulted in concentration-related inhibition of superoxide production induced by FMLP (30 nM) or phorbol myristate acetate (16 nM);-log IC50 values were 3.97 +/- 0.07 and 3.91 +/- 0.10, respectively. Changes in intracellular calcium ion concentration ([Ca2+]i) induced by FMLP (30 nM) were studied in fura-2-loaded human PMN. FMLP produced a transient calcium response, i.e. a peak followed by decay to a residual value above baseline. N-Acetylcysteine (333 microM) did not affect either basal [Ca2+]i values or changes in [Ca2+]i values after treatment with FMLP. Activation by phorbol myristate acetate caused a reduction in glutathione levels from 5.94 +/- 0.86 (control) to 1.84 +/- 0.51 nmol/3 x 10(6) cells (P < 0.05 compared with control). Pre-treatment with N-acetylcysteine (333 microM) fully reversed the reduction in glutathione levels induced by phorbol myristate acetate (4.83 +/- 0.68 nmol/3 x 10(6) cells; P > 0.05 compared with control). Exposure to t-butyl hydroperoxide (0.5 mM, 30 min) markedly increased malondialdehyde levels (from 0.03 +/- 0.02 to 0.73 +/- 0.07 nmol/10(6) cells), and index of lipid peroxidation. Malondialdehyde levels were significantly reduced in PMN treated with N-acetylcysteine (333 microM; 0.55 +/- 0.04 nmol/10(6) cells; P < 0.05 compared with untreated cells exposed to t-butyl hydroperoxide). In conclusion, N-acetylcysteine reduces superoxide generation in response to FMLP and phorbol myristate acetate and partially protects against lipid peroxidation in PMN from man. The protection afforded by N-acetylcysteine is not related to alteration of the intracellular calcium signal but might be effected by replenishment of the intracellular glutathione levels.

Effects of SCA40 on human isolated bronchus and human polymorphonuclear leukocytes: comparison with rolipram, SKF94120 and levcromakalim.

1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10) and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) > SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16; n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and PDE V (4.32 +/- 0.11; n = 4). 3. Human polymorphonuclear leukocytes (PMNs) stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP) produced a concentration-dependent superoxide anion generation and elastase release. SCA40 (1 nM-10 microM) produced a concentration-related inhibition of FMLP (30 nM approximately EC50)-induced superoxide production (-log IC50 = 5.48 +/- 0.10; n = 6) and elastase release (-log IC50 = 5.50 +/- 0.26; n = 6). Rolipram was an effective inhibitor of superoxide generation and elastase release (-log IC50 values approximately 8) while SKF94120 and levcromakalim were scarcely effective. 4. FMLP (30 nM) and thimerosal (20 microM) induced leukotriene B4 production and elevation of intracellular calcium concentration in human PMNs. The production of leukotriene B4 was inhibited by SCA40 in a concentration-related manner (-log IC50 = 5.94 +/- 0.22; n = 6) but SCA40 was less effective against the elevation of intracellular calcium. Rolipram was an effective inhibitor of leukotriene B4 synthesis (-log IC50 approximately 7) and intracellular calcium elevation (-log IC50 approximately 6) while SKF94120 and levcromakalim were scarcely effective. 5. It is concluded that SCA40 is an effective inhibitor of the inherent tone of human isolated bronchus. The bronchodilatation produced by SCA40 appears mainly related to PDE inhibition since the potency of SCA40 as a relaxant of human isolated bronchus was found to be close to its potency as inhibitor of PDE III activity isolated from human bronchus. In addition, SCA40 exhibited inhibitory effects on human PMN function stimulated by FMLP. These effects may be related to the ability of SCA40 to inhibit PDE IV from human PMNs while the contribution of PDE V inhibition is uncertain. We found no evidence of a role for levcromakalim-sensitive plasmalemmal K+-channels in human PMNs.

Inhibition of phosphodiesterase IV and intracellular calcium levels in human polymorphonuclear leukocytes.

Phosphodiesterase (PDE) isoenzyme type IV is the predominant cyclic AMP hydrolytic activity in polymorphonuclear leukocytes (PMNs). PDE IV inhibitors depress functional responses of PMNs but their influence on intracellular calcium concentration ([Ca2+]i) has not been extensively studied. The present study examined the effects of rolipram (a selective PDE IV inhibitor) on the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP)-induced changes of [Ca2+]i in fura-2 loaded human PMNs. Rolipram (1 nM-10 microM) did not alter basal [Ca2+]i values. fMLP (10 nM approximately EC50) produced a transient calcium response, i.e., a peak followed by decay to a residual value above baseline. Peak [Ca2+]i values after fMLP were not altered but a faster decay and a lower residual [Ca2+]i were observed in rolipram (0.1-10 microM)-treated cells. fMLP added after thimerosal (20 microM) produced a peak followed by a sustained oscillatory response. Rolipram (up to 10 microM) did not alter the peak but inhibited the sustained response (-log IC50 = 6.39 +/- 0.12). The inhibitory effects of rolipram may be due to alterations in the mobilization of Ca2+ produced by the increase in the cellular content of cyclic AMP. SKF94120 (a selective PDE III inhibitor) produced minor effects on the fMLP-induced calcium response. SCA40 (a mixed PDE III/IV/V inhibitor) produced similar effects but was less potent than rolipram. Reduction of the calcium response probably underlies the inhibition of PMN functions produced by PDE IV inhibitors.

Effect of serotonin and calcium in normal and sensitized guinea pig isolated trachea.

Tracheal strips from normal and actively sensitized guinea pigs were studied to determine the responses to serotonin (5-hydroxytryptamine, 5-HT; 1 nM-0.1 mM) and ouabain (0.1 microM-0.1 mM), and the effects of increasing the extracellular calcium (Cao) concentration on tonic contractions elicited by 5-HT. Sensitized trachea exhibited an increased responsiveness and sensitivity to 5-HT and ouabain. Increases in Cao to achieve final concentrations of 5, 10 and 20 mM caused concentration-related relaxations of normal and sensitized tissues contracted to a similar plateau level with 5-HT. Inhibition of the Na+/K(+)-ATPase by ouabain (10 microM) reversed the effects of Cao from relaxation to contraction in normal and sensitized tissues contracted with 5HT. Sensitized preparations showed reduced relaxations in response to Cao (10-20 mM), and sensitized, ouabain-treated, trachea showed augmented contractions to Cao (10-20 mM) when compared to normal tissues. These results demonstrate a decreased membrane-stabilizing effect of Cao in sensitized trachea and the implication of the Na+/K(+)-ATPase in the regulation of membrane stability by Cao, suggesting a possible relevance to those mechanisms underlying airway hyperreactivity.