Os 125 anos da psicanálise e a ética do psicanalista / 125 years of psychoanalysis and the ethics of the psychoanalyst

A autora apresenta um panorama da evolução cultural humana, partindo dos primórdios da humanidade até o aparecimento da psicanálise, no final do século XIX e começo do século XX. Introduz a figura de Sigmund Freud, o criador da psicanálise, e a trajetória desse novo saber, que traz à luz a instância do inconsciente. Fala também das principais obras freudianas, chegando até Jacques Lacan, no século XX, que faz uma releitura de Freud. Discute ainda o conceito de ética, salientando que a psicanálise tem uma ética própria, que é a ética do sujeito do inconsciente, a ética do bem dizer. Por fim, destaca o papel do analista na sociedade e as diversas aberturas que a psicanálise trouxe para o ser humano(AU)

The author presents an overview of human cultural evolution, starting from the beginnings of humanity, until the appearance of psychoanalysis, in the late 19th and early 20th centuries. It introduces the figure of Sigmund Freud, the creator of Psychoanalysis, and the trajectory of this new knowledge, which brings to light the instance of the unconscious. She also talks about the main Freudian works, reaching Jacques Lacan, in the 20th century, who rereads Freud. It also discusses the concept of Ethics, emphasizing that Psychoanalysis has its own ethics, which is the ethics of the subject of the unconscious, the ethics of saying this subject’s truth. Finally, she highlights the role of the analyst in society and the various openings that Psychoanalysis has brought to human beings(AU)

Lower respiratory tract microbiome composition and community interactions in smokers.

The lung microbiome impacts on lung function, making any smoking-induced changes in the lung microbiome potentially significant. The complex co-occurrence and co-avoidance patterns between the bacterial taxa in the lower respiratory tract (LRT) microbiome were explored for a cohort of active (AS), former (FS) and never (NS) smokers. Bronchoalveolar lavages (BALs) were collected from 55 volunteer subjects (9 NS, 24 FS and 22 AS). The LRT microbiome composition was assessed using 16S rRNA amplicon sequencing. Identification of differentially abundant taxa and co-occurrence patterns, discriminant analysis and biomarker inferences were performed. The data show that smoking results in a loss in the diversity of the LRT microbiome, change in the co-occurrence patterns and a weakening of the tight community structure present in healthy microbiomes. The increased abundance of the genus Ralstonia in the lung microbiomes of both former and active smokers is significant. Partial least square discriminant and DESeq2 analyses suggested a compositional difference between the cohorts in the LRT microbiome. The groups were sufficiently distinct from each other to suggest that cessation of smoking may not be sufficient for the lung microbiota to return to a similar composition to that of NS. The linear discriminant analysis effect size (LEfSe) analyses identified several bacterial taxa as potential biomarkers of smoking status. Network-based clustering analysis highlighted different co-occurring and co-avoiding microbial taxa in the three groups. The analysis found a cluster of bacterial taxa that co-occur in smokers and non-smokers alike. The clusters exhibited tighter and more significant associations in NS compared to FS and AS. Higher degree of rivalry between clusters was observed in the AS. The groups were sufficiently distinct from each other to suggest that cessation of smoking may not be sufficient for the lung microbiota to return to a similar composition to that of NS.

Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction.

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days. Markers of inflammation, including interleukin-6 (IL6), interleukin-8 (IL8) and matrix metalloproteinase-9 (MMP9) mRNAs, as well as MMP-9 activity and mucin 5AC (MUC5AC) expression levels, were also elevated in nasal samples from volunteers who vaped VG-containing e-liquids. In sheep, exposures to VG e-cig aerosols for five days increased mucus concentrations and MMP-9 activity in tracheal secretions and plasma levels of transforming growth factor-beta 1 (TGF-ß1). In vitro exposure of HBECs to VG e-cig aerosols for five days decreased ciliary beating and increased mucus concentrations. VG e-cig aerosols also reduced CFTR function in HBECs, mechanistically by reducing membrane fluidity. Although VG e-cig aerosols did not increase MMP9 mRNA expression, expression levels of IL6, IL8, TGFB1, and MUC5AC mRNAs were significantly increased in HBECs after seven days of exposure. Thus, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration.

O medo sem face na pandemia da covid-19 / The faceless fear of covid 19 pandemic

O medo é uma emoção não patológica, universal, própria dos seres mais elevados da escala animal. Tem sua origem na angústia e no desamparo. É caracterizado, diferentemente da angústia, como tendo um objeto identificável. Na pandemia da covid-19, seu causador, o coronavírus, não é facilmente verificável, o que tornou o medo muito mais próximo da angústia. Todos os outros seres humanos são vistos como possíveis portadores do mal, o que nos faz vulneráveis ao contato humano, em todas as situações(AU)

Fear is a non-pathological, universal emotion, typical of the highest beings of the animal scale. It has its origin in anguish and helplessness. It is characterized, unlike anxiety, as having an identifiable object. In the covid 19 pandemic, its cause, the corona virus, is not easily verifiable, which made fear much closer to anguish. All other human beings are seen as possible carriers of illness, which makes us vulnerable to human contact in all situations(AU)

Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion.

The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in an in vitro model and a small clinical trial. Primary human bronchial epithelial cells (HBECs) were differentiated at the air-liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-ß1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure. Parameters of mucociliary clearance were evaluated by measuring airway surface liquid volumes, mucus concentrations, and conductance of cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated and voltage-dependent potassium (BK) channels. Nasal cells were collected from study participants and expression of MUC5AC, TGF-ß1, and MMP-9 mRNAs was measured before and after losartan treatment. In vitro, CS exposure of HBECs caused a significant increase in mRNA expression of MUC5AC and TGF-ß1 and MMP-9 activity and decreased CFTR and BK channel activities, thereby reducing airway surface liquid volumes and increasing mucus concentrations. Treatment of HBECs with losartan rescued CS-induced CFTR and BK dysfunction and caused a significant decrease in MUC5AC expression and mucus concentrations, partially by inhibiting TGF-ß signalling. In a prospective clinical study, cigarette smokers showed significantly reduced mRNA expression levels of MUC5AC, TGF-ß1, and MMP-9 in the upper airways after 2 months of losartan treatment. Our findings suggest that losartan may be an effective therapy to reduce inflammation and mucus hypersecretion in CS-induced chronic airway diseases.

O estranho dentro de nós, a intolerância à diferença / The uncanny inside us, the intolerance to difference

A autora faz uma revisão do texto Das Unheimliche, apontando para o fato de que, com a noção freudiana de inconsciente, o aparecimento do estranho, do infamiliar no psiquismo perde seu aspecto patológico e é parte integrante do mesmo. Como somos seres divididos, o estranho está dentro de nós. Aborda a questão atual dos estrangeiros e migrantes, principalmente daqueles que voltam para as matrizes colonizadoras. Tal fato, a seu ver, se constitui num retorno do recalcado, pois as pulsões primitivas de ódio, vividas de parte a parte, se reatualizam nas ações de agora. Finaliza dizendo que a psicanálise é subversiva e libertária, e pode trazer uma luz para essa intolerância à diferença. Quanto mais somos conscientes de nossas estranhezas, mais podemos tolerar sua presença no outro(AU)

The author makes a review of the text “Das Unheimliche”, pointing to the fact that with the Freudian notion of unconscious, the appearance of the uncanny in the psyche loses its pathological aspect and is an integrant part of it. As we are divided beings, the uncanny is unside us. She adresses the current issue of foreigners and migrants especially those who return to colonizing matrices. This fact, in her opinion, constitutes a return of repressed, because the primitive hatred drives, lived from part to part, are reupdated in such situation. She concludes by saying that Psychoanalysis is subversive and libertarian, so can bring a light to this intolerance to difference. The more we are conscious of our uncanny aspects, the more we can tolerate their presence in the other(AU)

The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy. A Pilot Clinical Trial.

Rationale: Augmentation therapy with intravenous AAT (alpha-1 antitrypsin) is the only specific therapy for individuals with pulmonary disease from AAT deficiency (AATD). The recommended standard dose (SD; 60 mg/kg/wk) elevates AAT trough serum levels to around 50% of normal; however, outside of slowing emphysema progression, its effects in other clinical outcomes have not been rigorously proven.Objectives: To evaluate the biological effects of normalizing AAT trough levels with double-dose (DD) therapy (120 mg/kg/wk) in subjects with AATD already receiving SD therapy.Methods: Clinically stable subjects were evaluated after 4 weeks of SD therapy, followed by 4 weeks of DD therapy, and 4 weeks after return to SD therapy. At the end of each phase, BAL fluid (BALF) and plasma samples were obtained.Measurements and Main Results: DD therapy increased trough AAT levels to normal and, compared with SD therapy, reduced serine protease activity in BALF (elastase and cathepsin G), plasma elastase footprint (Aα-Val360), and markers of elastin degradation (desmosine/isodesmosine) in BALF. DD therapy also further downregulated BALF ILs and cytokines including Jak-STAT (Janus kinases-signal transducer and activator of transcription proteins), TNFα (tumor necrosis factor-α), and T-cell receptor signaling pathways, cytokines involved in macrophage migration, eosinophil recruitment, humoral and adaptive immunity, neutrophil activation, and cachexia. On restarting SD after DD treatment, a possible carryover effect was seen for several biological markers.Conclusions: Subjects with AATD on SD augmentation therapy still exhibit inflammation, protease activity, and elastin degradation that can be further improved by normalizing AAT levels. Higher AAT dosing than currently recommended may lead to enhanced clinical benefits and should be explored further.Clinical trial registered with www.clinicaltrials.gov (NCT01669421).

Sobre a transmissão da psicanálise nas instituições psicanalíticas / On the transmission of psychoanalysis in psychoanalytical institutions

O artigo fala em favor da formação psicanalítica em instituições que existem para tal fim, contrapondo à formação de analistas na universidade. Aponta também medidas que podem aprimorar a transmissão da psicanálise nas instituições psicanalíticas, tais como a análise pessoal desde o princípio da formação e o acompanhamento de um referente para cada participante da formação, tendo em vista o acolhimento que vise o sujeito em questão e não apenas o aluno.(AU)

The article deals with Analytical studies in Institutions that exist for this purpose, against the formation of analysts by the University. It also points out measures that can improve the transmission of psychoanalysis in the specific institutions such as personal analysis from its beginning of training and the monitoring by a referential for each participant, aiming the reception centered in the subject and not just the student.(AU)

A falta que consome / The lack that consumes

Vivemos hoje numa sociedade hedonista, onde o prazer é buscado a qualquer custo. Em decorrência disso, assiste-se a um aumento exacerbado do consumo, como fonte imediata de felicidade. Hoje a moralidade se traduz, para o consumidor, em usufruir o máximo prazer da vida. Em sintonia com a moral do espetáculo, estar feliz não é apenas sentir-se sentimentalmente repleto, mas é preciso se ver semelhante aos ‘vencedores’, aos ‘visíveis’, aos astros midiáticos. A autora usa os exemplos do funk ostentação e do consumo ilegítimo dos políticos corruptos que se utilizam do dinheiro do povo para preencher seu bolso e seu vazio existencial (sua falta). Quando esse espaço fica tomado, vem a angústia. Se ela é obturada, o desejo não aparece, e sem o desejo tem lugar uma repetição interminável de uma mesma cadeia, que o aprisiona e o consome. Os que não mais desejam se acham consumidos ou desaparecidos enquanto sujeitos. Aí se pode falar da falta que consome.(AU)

We live in a hedonistic society, where pleasure is sought at all costs. As a result, there is an exacerbated increase in consumption, as an immediate source of happiness. Today, morality is, for the consumer, to enjoy the maximum pleasure of life. In tune with the morality of the spectacle, to be happy is not only to feel sentimentally fulfilled, but one must look like the 'winners', the 'visible', the mediatic stars. The author uses the examples of funk ostentation and the illegitimate consumption of corrupt politicians who use the money of the people to fill their own pockets and their existential emptiness (their lack). When this space is taken, anguish comes. If it is filled, desire does not appear, and without desire there takes place an endless repetition of the same chain, which imprisons and consumes that desire. Those who no longer desire are consumed or disappeared as subjects. Then we can talk about the lack that consumes.(AU)

Raízes da violência no Brasil: impasses e possibilidades / Roots of violence in Brazil: impasses and possibilities

Atualmente a violência aparece de várias formas no Brasil. Rapidamente o Brasil passou de um país agrícola para industrializado, o que resultou em amplo êxodo rural e explosão demográfica nas grandes cidades. O Brasil enfrenta hoje uma enorme disparidade social e econômica, acrescida de uma corrupção endêmica do governo, além do nepotismo e falta de planejamento social. As raízes de tal violência podem ser encontradas na herança arcaica, que tem formado a identidade brasileira desde nossos primeiros dias. O interesse dos colonizadores de então era extrair riquezas, sem considerar o estabelecimento da nação. Essa exploração foi sempre feita pela força e pela violência através do trabalho escravo dos índios nativos e dos negros importados da África. Como um estado, o Brasil ficou exposto à lei do pai primevo e à ausência de um pai simbólico, que poderia garantir a seu povo uma identidade mais estável, a qual apenas a lei paterna pode conceder. Será possível reformular a herança arcaica, reconstruindo a imagem do pai que falta, sem recorrer a um falso salvador da pátria? Será possível construir uma sociedade mais igualitária, que possa propiciar condições verdadeiras de cidadania, a fim de tornar cada cidadão, na medida do possível, o protagonista de sua própria história?(AU)

Nowadays, violence appears in various forms in Brazil. From an agricultural country, Brazil became rapidly industrialized, which resulted in large rural exodus and explosion of population density in major cities. Brazil faces today a great social and economic disparity, added to endemic corruption of government, nepotism and lack of social planning. The roots of such violence can be found in our archaic heritage that has been forming Brazilian identity since its early days. The interest of former colonizers was to extract wealth, without regarding the establishment of a nation. This exploitation has been always done by force and violence, with the slave labor of native Indians and imported black people. As a state Brazil was exposed to the primal father’s law, and to the absence of a symbolic father, who could have provided his people with a more stable identity, only given by the paternal law. Is it possible to reframe archaic heritage, rebuilding the missing father image without resorting to a false savior of the fatherland? Is it possible to construct a more equitable society that could propitiate true conditions of citizenship in order to make every citizen, to the extent possible, the protagonist of his own history?(AU)

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.

Chronic inflammation is a hallmark of cystic fibrosis (CF) and associated with increased production of transforming growth factor (TGF) ß and interleukin (IL)-8. α-klotho (KL), a transmembrane or soluble protein, functions as a co-receptor for Fibroblast Growth Factor (FGF) 23, a known pro-inflammatory, prognostic marker in chronic kidney disease. KL is downregulated in airways from COPD patients. We hypothesized that both KL and FGF23 signaling modulate TGF ß-induced IL-8 secretion in CF bronchial epithelia. Thus, FGF23 and soluble KL levels were measured in plasma from 48 CF patients and in primary CF bronchial epithelial cells (CF-HBEC). CF patients showed increased FGF23 plasma levels, but KL levels were not different. In CF-HBEC, TGF-ß increased KL secretion and upregulated FGF receptor (FGFR) 1. Despite increases in KL, TGF-ß also increased IL-8 secretion via activation of FGFR1 and Smad 3 signaling. However, KL excess via overexpression or supplementation decreased IL-8 secretion by inhibiting Smad 3 phosphorylation. Here, we identify a novel signaling pathway contributing to IL-8 secretion in the CF bronchial epithelium with KL functioning as an endocrine and local anti-inflammatory mediator that antagonizes pro-inflammatory actions of FGF23 and TGF-ß.

Airway and Pulmonary ß2-Adrenergic Vasodilatory Function in Current Smokers and Never Smokers.

BACKGROUND: Cigarette smoking has been associated with diminished vasodilatory function in the airway circulation. It is possible that cigarette smoking similarly affects the pulmonary circulation before resting pulmonary circulatory abnormalities become manifested. The aim of this study was to compare the acute effect of inhaled albuterol on airway and pulmonary hemodynamic function as an index of ß2-adrenoceptor-mediated vasodilation in smokers and never smokers. METHODS: In 30 adults, airway and pulmonary vascular function was assessed before and 15 min after albuterol inhalation (270 µg). From mean systemic arterial pressure, cardiac output, airway blood flow, and mean pulmonary arterial pressure, airway vascular resistance (AVR) and pulmonary vascular resistance (PVR) were derived. RESULTS: Albuterol induced a substantial drop in mean (± SE) PVR (-67.2% ± 5%), with no difference between groups. In contrast, the albuterol-induced decrease in AVR was significantly greater in never smokers than in smokers (-28.6% ± 3% vs -3.1% ± 6%; P < .02). CONCLUSIONS: These results are consistent with a dysfunction in a ß2-adrenergic signaling pathway mediating vasorelaxation in the airway circulation of current smokers. The vasodilatory deficit in the airway circulation but not in the pulmonary circulation could be related to local differences in the impact of cigarette smoke on the vascular endothelium.

Hispanics/Latinos With Type 2 Diabetes Have Functional and Symptomatic Pulmonary Impairment Mirroring Kidney Microangiopathy: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE: Type 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored. RESEARCH DESIGN AND METHODS: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18-74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses. RESULTS: Among Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1 3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81 [3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P < 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P < 0.001), 6% lower FEV1 (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/Latinos with lung disease. CONCLUSIONS: Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further.

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Alguns impasses da clínica psicanalítica contemporânea e a sua operacionalização pelo desejo do analista / Some impasses of the contemporary psychoanalytic clinic and its management by the desire of the analyst

O texto discute alguns dos impasses encontrados na clínica psicanalítica contemporânea, que vão afetar as relações tranferenciais e a condução do tratamento. Como modo de abordar essa clínica, Lacan propõe sua teorização sobre o desejo do analista, permitindo ao analisante repetir e elaborar seus próprios conflitos na transferência. O analista atua como uma função operadora, fazendo semblante de objeto a, empregando um saber entusiasmado: o gaio saber.(AU)

This text discusses some of the impasses found in contemporary psychoanalytic clinic, which will affect the transference relations and the conduct of the treatment. As the clinical management mode, Lacan proposes his theory of the desire of the analyst, allowing the analysand to repeat and to work through in the transference. The analyst takes the place of a function operator, making semblance of the object a, using enthusiastic knowledge, the so called gay science, or joyful science.(AU)

Trauma e identidade brasileira / Trauma and brazilian identity

A autora faz um rastreamento das origens da sociedade brasileira, salientando os traumas que, como uma herança arcaica, constituíram nossa identidade. Aborda mais especificamente o povoamento desordenado do território brasileiro, com deserdados da sorte e posteriormente a instituição da escravidão, com suas marcas indeléveis. Relembra a história do primeiro e segundo reinados e da república, as ditaduras da era Vargas e do golpe militar de 1964, além da morte de Tancredo Neves na retomada da democracia. A corrupção atual parece ser um legado de um estado onde prevalece a lei do pai primevo, na qual o pacto social é pouco respeitado. Após analisar alguns traços da identidade brasileira, questiona se é possível ressignificar o pai faltante e se essas retificações podem atingir o inconsciente coletivo.(AU)

The author traces the origins of Brazilian society, stressing the traumas that, as an archaic heritage have constituted our identity. Deals more specifically with the disorderly settlement of the Brazilian territory, with disinherited people, and later the constitution of slavery, with its indelible mark. Recalls the history of the first and the second Kingdom, and the establishment of the Republic and also the dictatorship of era Vargas and the military coup of 1964, and the death of Tancredo Neves, in the return to democracy. The current corruption appears to be a legacy of a state where the prevailing law is that of the primal father, in which the social pact is little respected. After analyzing some aspects of Brazilian identity, questions whether it is possible to reframe the missing father and whether these corrections can achieve the collective unconscious.(AU)

Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

BACKGROUND: In vitro and animal experiments have shown that the transport and signaling of ß2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic ß2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. METHODS: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed. RESULTS: Mean ± SE EBC pH (units) and ΔQ̇aw (µl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing). CONCLUSIONS: Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic ß2-adrenergic agonists during airway disease exacerbations associated with changes in pH. TRIAL REGISTRATION: Registered at clinicaltrials.gov: NCT01216748 .

Acute effect of an inhaled glucocorticosteroid on albuterol-induced bronchodilation in patients with moderately severe asthma.

BACKGROUND: We have previously shown that in patients with asthma a single dose of an inhaled glucocorticosteroid (ICS) acutely potentiates inhaled albuterol-induced airway vascular smooth muscle relaxation through a nongenomic action. An effect on airway smooth muscle was not seen, presumably because the patients had normal lung function. The purpose of the present study was to conduct a similar study in patients with asthma with airflow obstruction to determine if an ICS could acutely also potentiate albuterol-induced airway smooth muscle relaxation in them. METHODS: In 15 adult patients with asthma (mean ± SE baseline FEV1, 62% ± 3%), the response to inhaled albuterol (180 µg) was assessed by determining the change in FEV1 (ΔFEV1) for airway smooth muscle and in airway blood flow (ΔQaw) for airway vascular smooth muscle measured 15 min after drug inhalation. Using a double-blind design, the patients inhaled a single dose of the ICS mometasone (400 µg) or placebo simultaneously with or 30 min before albuterol inhalation. RESULTS: After simultaneous drug administration, mean ΔFEV1 was 0.20 ± 0.05 L (10%) after placebo and 0.32 ± 0.04 L (19%) after mometasone (P < .05); mean ΔQaw was -2% after placebo and 30% after mometasone (P < .005). When mometasone or placebo was administered 30 min before albuterol, there was a lesser and insignificant difference in ΔFEV1 between the two treatments, whereas the difference in ΔQaw remained significant. CONCLUSIONS: This pilot study showed that in adult patients with asthma with airflow obstruction, a single standard dose of an ICS can acutely increase the FEV1 response to a standard dose of inhaled albuterol administered simultaneously. The associated potentiation of albuterol-induced vasodilation in the airway was of greater magnitude and retained when the ICS was administered 30 min before albuterol. The clinical significance of this observation will have to be established by a study involving a larger patient cohort. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01210170; URL: www.clinicaltrials.gov.

Immediate antiinflammatory effects of inhaled budesonide in patients with asthma.

BACKGROUND: In patients with asthma, single doses of inhaled glucocorticosteroids (ICS) have been reported to have antiinflammatory actions that can be detected several hours after drug administration. However, the onset and duration of the effect have not been investigated. We therefore measured airway blood flow ([Formula: see text]aw) as an index of airway inflammation to determine the time course and dose dependence of the antiinflammatory action of an ICS in 20 patients with moderate asthma receiving regular ICS treatment. METHODS: [Formula: see text]aw and spirometry were measured before and serially for 360 minutes after a single inhaled dose of 360 µg, 720 µg, and 1,440 µg budesonide or placebo as well as after four repetitive 720-µg budesonide doses given 30 minutes apart. RESULTS: Baseline mean [Formula: see text]aw was increased and FEV1 was decreased without significant differences among the 5 treatment days. After budesonide inhalation, there was a transient, dose-dependent decrease in mean [Formula: see text]aw from 12 to 21%, with significant differences from baseline at 60 and 90 minutes for the 720-µg and 1,440-µg doses (P < 0.05). Thirty minutes after four repetitive budesonide administrations, mean [Formula: see text]aw was 28% below baseline (P < 0.05) and remained 11% below baseline after 270 minutes. There was no change in mean FEV1 after any of the treatments. CONCLUSIONS: In subjects with moderate asthma who use ICS regularly, inhaled budesonide caused a transient dose-dependent vasoconstriction in the airway, thereby reversing one manifestation of airway inflammation. These results suggest that a pure controller medication can have immediate beneficial effects not paralleled by changes in airflow. Clinical trial registered with www.clinicaltrials.gov (NCT 01219738).