[Ion transporters in the lungs. Use as therapeutic targets]. / Transportadores de iones en pulmón. Uso como dianas terapéuticas.

The chloride channels, sodium and bicarbonate channels, and aquaporin water channels are coordinated to maintain the airway surface liquid that is necessary for mucociliary clearance. The general mechanism for the transport of electrolytes and fluids depends mainly on the differential expression and distribution of ion transporters and pumps. Ions and water move through the paracellular or transcellular pathways. The transcellular route of electrolyte transport requires an active transport (dependent on ATP) or passive (following electrochemical gradients) of ions. The paracellular pathway is a passive process that is ultimately controlled by the predominant transepithelial electrochemical gradients. Cystic fibrosis is a hereditary disease that is produced by mutations in the gene that encode cystic fibrosis transmembrane conductance regulatory protein (CFTR) that acts as a chloride channel and performs functions of hydration of periciliary fluid and maintenance of luminal pH. The dysfunction of the chlorine channel in the respiratory epithelium determines an alteration in the bronchial secretions, with an increase in its viscosity and alteration of the mucociliary clearance and that associated with infectious processes can lead to irreversible lung damage. CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease, and bronchial hyperreactivity in asthma. There are drugs that exploit physiological mechanisms in the transport of ions with a therapeutic objective.

Los canales de cloruros, de sodio, de bicarbonato y los de agua (aquaporinas) se coordinan para mantener la cubierta líquido superficial de las vías respiratorias, que es necesaria para el aclaramiento mucociliar. El mecanismo general para el transporte de electrolitos y agua depende principalmente de la expresión diferencial y distribución de los transportadores y bombas de iones. Los iones y el agua se mueven a través de las vía paracelular o transcelular. La ruta transcelular del transporte de electrolitos requiere un transporte activo (dependiente de ATP) o pasivo (siguiendo gradientes electroquímicos) de iones. La ruta paracelular es un proceso pasivo que está controlado, en última instancia, por los gradientes electroquímicos transepiteliales predominantes. La fibrosis quística es una enfermedad hereditaria que se produce por mutaciones en el gen que codifica la proteína reguladora de la conductibilidad transmembrana de la fibrosis quística (CFTR) que actúa como un canal de cloro y cumple funciones de hidratación del líquido periciliar y mantenimiento del pH luminal. La disfunción del canal de cloro en el epitelio respiratorio determina una alteración en las secreciones bronquiales, con aumento de su viscosidad y alteración de la depuración mucociliar y que asociado a procesos infecciosos puede conducir a daño pulmonar irreversible. La disfunción del CFTR, también se ha visto implicado en la patogénesis de la pancreatitis aguda, en la enfermedad pulmonar obstructiva crónica y la hiperreactividad en el asma. Existen fármacos que aprovechan los mecanismos fisiológicos en el transporte de iones, con un objetivo terapéutico.

Transportadores de iones en pulmón: Uso como dianas terapéuticas / Ion transporters in the lungs. Use as therapeutic targets

Los canales de cloruros, de sodio, de bicarbonato y los de agua (aquaporinas) se coordinan para mantener la cubierta líquido superficial de las vías respiratorias, que es necesaria para el aclaramiento mucociliar. El mecanismo general para el transporte de electrolitos y agua depende principalmente de la expresión diferencial y distribución de los transportadores y bombas de iones. Los iones y el agua se mueven a través de las vía paracelular o transcelular. La ruta transcelular del transporte de electrolitos requiere un transporte activo (dependiente de ATP) o pasivo (siguiendo gradientes electroquímicos) de iones. La ruta paracelular es un proceso pasivo que está controlado, en última instancia, por los gradientes electroquímicos transepiteliales predominantes. La fibrosis quística es una enfermedad hereditaria que se produce por mutaciones en el gen que codifica la proteína reguladora de la conductibilidad transmembrana de la fibrosis quística (CFTR) que actúa como un canal de cloro y cumple funciones de hidratación del líquido periciliar y mantenimiento del pH luminal. La disfunción del canal de cloro en el epitelio respiratorio determina una alteración en las secreciones bronquiales, con aumento de su viscosidad y alteración de la depuración mucociliar y que asociado a procesos infecciosos puede conducir a daño pulmonar irreversible. La disfunción del CFTR, también se ha visto implicado en la patogénesis de la pancreatitis aguda, en la enfermedad pulmonar obstructiva crónica y la hiperreactividad en el asma. Existen fármacos que aprovechan los mecanismos fisiológicos en el transporte de iones, con un objetivo terapéutico.

The chloride channels, sodium and bicarbonate channels, and aquaporin water channels are coordinated to maintain the airway surface liquid that is necessary for mucociliary clearance. The general mechanism for the transport of electrolytes and fluids depends mainly on the differential expression and distribution of ion transporters and pumps. Ions and water move through the paracellular or transcellular pathways. The transcellular route of electrolyte transport requires an active transport (dependent on ATP) or passive (following electrochemical gradients) of ions. The paracellular pathway is a passive process that is ultimately controlled by the predominant transepithelial electrochemical gradients. Cystic fibrosis is a hereditary disease that is produced by mutations in the gene that encode cystic fibrosis transmembrane conductance regulatory protein (CFTR) that acts as a chloride channel and performs functions of hydration of periciliary fluid and maintenance of luminal pH. The dysfunction of the chlorine channel in the respiratory epithelium determines an alteration in the bronchial secretions, with an increase in its viscosity and alteration of the mucociliary clearance and that associated with infectious processes can lead to irreversible lung damage. CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease, and bronchial hyperreactivity in asthma. There are drugs that exploit physiological mechanisms in the transport of ions with a therapeutic objective.

Topical Nigella Sativa for nasal symptoms in elderly.

OBJECTIVE: To compare the effects of intranasal application of black seed (Nigella Sativa) oil (NSO) and isotonic sodium chloride solution (ISCS) on nasal symptoms of the elderly. METHODS: In this prospective, crossover randomized controlled trial, 42 geriatric patients with nasal dryness and related symptoms were randomized to receive either 2 weeks of isotonic sodium chloride solution (ISCS) followed by 2 weeks of N. sativa oil (NG oil) or the same treatment in the opposite order. There was a washout period of 3 weeks in between the treatment periods. Subjective symptoms including nasal dryness, burning, obstruction, itching and crusting were evaluated by a visual analog scale. Mucociliary function was evaluated with saccharin test. RESULTS: Nasal dryness, obstruction and crusting improved significantly with the use of NSO compared to ISCS without any evidence of relevant carryover effects (p<0.05 for all for the difference in treatment). There was no significant difference between the effect of NSO and ISCS on nasal burning and itching (p>0.05 for all). There was no change in mucociliary clearance during any of the treatment periods. CONCLUSION: NSO is a better alternative to ISCS to treat nasal mucosa symptoms due to aging.

Ensayo clínico aleatorizado de técnicas de aclaramiento mucociliar en niños con bronquiectasias sin fibrosis quística / Randomized clinical trial of mucociliary clearance techniques in non-cystic fibrosis bronchiectasis in children

Objetivo Evaluar la eficacia de las presiones manuales espiratorias lentas y aumentos de flujo espiratorio (AFE) combinadas con insuflación-exuflación mecánica (I-EM) y tos asistida (TA), frente al ciclo activo de técnicas respiratorias (CATR) en bronquiectasia infantil estable sin fibrosis quística (FQ).Material y métodos Ensayo clínico aleatorizado en 2 grupos de 6 niños (edad 8,1±1,3) que reciben 2 sesiones de fisioterapia respiratoria (FR) al mes. Las principales variables de estudio son: peso de esputo recogido tras sesión de FR y medición de la función pulmonar al inicio del estudio y a los 12 meses; capacidad vital forzada (CVF), volumen espiratorio máximo en 1 s (VEMS o FEV1) y el flujo espiratorio forzado entre el 25%-75% de la CVF (FEF25-75%). Asimismo, evaluamos el número de ingresos y exacerbaciones infecciosas y el impacto de la tos en la calidad de vida con el Leicester Cough Questionnaire (LCQ), al inicio y al final del estudio. Resultados El peso del esputo y el FEF25-75%, aumenta significativamente con las presiones manuales espiratorias lentas, AFE combinados con I-E M y TA, frente al CATR, en nuestra muestra. No hay diferencias significativas en cuanto a FEV1 y CVF. El número de exacerbaciones disminuyó en ambos grupos con respecto al año anterior (sin tratamiento de FR), y la puntuación total del LCQ. Conclusión Las presiones manuales espiratorias lentas, AFE combinados con I-E M y TA, para la permeabilización de la vía aérea en niños con bronquiectasias sin FQ, producen beneficios significativos en comparación al CATR (AU)

Objective To evaluate effectiveness of manual expiratory pressure and expiratory flow increase (EFI) combined with mechanical insufflation-exsufflation (MI-E) and assisted coughing (AC) versus active cycle of breathing techniques (ACBT) in stable bronchiectasis children without cystic fibrosis (CF).Material and methods Randomized clinical trial with 2 groups of 6 children (age 8.1±1.3) who received of respiratory physiotherapy (RP) sessions twice a month. The main endpoints studied are: weight of sputum collected after each session of RP and lung function measurements at baseline and 12 months, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow between 25%-75% of FVC (FEF25-75%). We also evaluated the number of visits to emergency department, infective exacerbations and the impact of cough on quality of life with the Leicester Cough Questionnaire (LCQ), at the beginning and the end of study. Results The weight of sputum and FEF25-75% increase significantly with manual expiratory pressure, EFI combined with MI-E and AC versus ACBT in our sample. There are no significant differences in FEV1 and FVC. Number of exacerbations decreased in both groups compared to the previous year (without CP treatment), and total score of the LCQ. Conclusion Slow manual expiratory pressure, EFI combined with MI-E and AC for airway permeabilization in children with non-CF bronchiectasis produce significant benefits compared to ACBT (AU)

Long-term efficacy of microdebrider-assisted inferior turbinoplasty with lateralization for hypertrophic inferior turbinates in patients with perennial allergic rhinitis.

OBJECTIVES: The aim of the study was to evaluate the long-term efficacy of microdebrider-assisted inferior turbinoplasty with lateralization (MAITL) compared to submucosal resection for hypertrophic inferior turbinates. STUDY DESIGN: Surgical outcomes were evaluated with respect to visual analogue scale, anterior rhinomanometry, and saccharin test results. METHODS: From January 2002 to December 2006 inclusively, 160 patients with perennial allergic rhinitis and hypertrophic inferior turbinates were enrolled into this study. The patients, all suffering from chronic nasal obstruction, were randomly classified into two groups, MAITL group or SR group, each comprised of 80 patients. Ten patients who did not display any nasal discomfort served as normal controls. For the submucosal resection group, patients underwent submucosal resection of the inferior turbinate, whereas patients in the MAITL group underwent microdebrider-assisted inferior turbinoplasty with lateralization. Assessments (visual analogue scale, anterior rhinomanometry, and saccharin test) were conducted prior to the surgery and 1, 2, and 3 years after completion of surgery. RESULTS: Compared to preoperative values, subjective complaints including nasal obstruction, sneezing, rhinorrhea, and snoring improved significantly in both groups at 1, 2, and 3 years after surgery in both groups (P < .05 for all). Rhinomanometric assessment also showed significant improvement at 1, 2, and 3 years postoperatively in both groups (P < .05 for all). Saccharin transit time was significantly decreased (P < .05 for all) compared to preoperative values 1, 2, and 3 years after surgery in both groups. CONCLUSION: Microdebrider-assisted inferior turbinoplasty with lateralization appears to be as effective as submucosal resection at relieving nasal symptoms and decreasing total nasal resistance and saccharin transit times for more than 3 years in patients with perennial allergic rhinitis who have had substantial nasal obstruction.

The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearance.

NIGELLA SATIVA L. has many effects including those on the gastrointestinal tract and trachea and is, therefore, used in the Mediteranean area and in India/Pakistan. Our aim was to investigate the effect of two main constituents, nigellone and thymoquinone, on trachea (antispasmodic effect) and their influence on respiratory clearance. The effects on Ba (2+)-, carbachol- and leukotriene-induced trachea contractions and the transport of the fluorescence dye rhodamin B concerning ciliary action in the tracheal area were investigated using a microdialysis technique. Nigellone and high concentrations of thymoquinone had a concentration-dependent inhibitory effect on the trachea when being contracted by the depolarizing effect of Ba (2+). The trachea contractions induced by leukotriene-d (4) were inhibited by nigellone and by thymoquinone. The cholinergic system (stimulation by carbachol) was hardly involved. The rate of ciliary clearance (mucociliary transport) was slightly modified by a high thymoquinone concentration (153.0 vs. 505.0 sec/12 mm distance, respectively), and was highly increased by nigellone (217.5 vs. 505.0 sec/12 mm distance). In conclusion, this study provides evidence for an antispasmodic effect and an increase in mucociliary clearance for nigellone but not for thymoquinone. Altogether the data indicate that nigellone but not thymoquinone may be useful in treatment of different respiratory diseases.

Noves propostes terapèutiques en fisioteràpia de les malalties respiratòries infantils / No disponible

Fonament. La fisioteràpia respiratòria infantil és unaespecialitat fonamentada en evidències científiques, àmpliament desenvolupada a la resta de països europeus ique comença a incorporar-se en el nostre país.Objectiu. Donar a conèixer un nou model de fisioteràpiarespiratòria infantil, científicament validat i complementari al tractament mèdic, que té com a objectiu el drenatge de secrecions de les vies aèries intra i extratoràciques en nadons i infants.Mètode. S'ha fet una revisió bibliogràfica dels darrersquinze anys de les malalties respiratòries infantils, la seva incidència, el tractament mèdic i fisioterapèutic i dels nous abordatges terapèutics.Resultats. Els darrers deu anys ha tingut lloc un canvien les avaluacions, els diagnòstics i les tècniques de tractament que utilitzen els fisioterapeutes per tractar les malalties respiratòries infantils. Aquests tractaments basats en evidències científiques han demostrat que les tècniques convencionals, com el drenatge postural, el repic (clapping), etc. no aconsegueixen eliminar secrecions bronquials;per contra, les tècniques basades en les modificacionsdel flux espiratori obtenen millors resultats i generenmenys complicacions secundàries.Conclusions. L'evolució de les professions sanitàriespassa per la incorporació de tractaments fonamentats enevidències científiques que validen les teràpies aplicades als pacients. Els fisioterapeutes respiratoris han fet un esforç molt important en investigació científica els darrers anys que cal considerar i incorporar en pediatria

No disponible

Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties.

The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal drug delivery. The objective of the present investigation was to develop a mucoadhesive in situ gel with reduced nasal mucociliary clearance in order to improve the bioavailability of the antiemetic drug, metoclopramide hydrochloride (MCP HCl). The in situ gelation upon contact with nasal mucosa was conferred via the use of the thermogelling poloxamer 407 whereas mucoadhesion and drug release enhancement were modulated via the use of mucoadhesive and polyethylene glycol (PEG) polymers respectively. The results revealed that the different mucoadhesives augmented the gel viscosity but reduced its sol-gel transition temperatures (T(sol-gel)) and the drug release. The inclusion of PEG counteracted the effect of the mucoadhesive polymers whereby it decreased the gel consistency and increased the T(sol-gel) as well as the in vitro drug release. The formulations with favorable sol-gel transition temperatures (25-32 degrees C) and high in vitro drug release (100% release in 60 min) were also rheologically stable upon storage. The mucoadhesiveness test was performed in vivo in rats, results showed that the carbopol-containing in situ gel prolonged the mucociliary transport time from 10 min (control solution) to 52 min (mucoadhesive gel) and maintained nasal mucosal integrity after 14-days application. The bioavailability study in rabbits revealed that the absolute bioavailability of MCP HCl was significantly increased from 51.7% in case of the oral drug solution to 69.1% in case of the nasal in situ gel. The study point to the potential of mucoadhesive nasal in situ gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved drug bioavailability.

Forced expiratory technique, directed cough, and autogenic drainage.

In health, secretions produced in the respiratory tract are cleared by mucociliary transport, cephalad airflow bias, and cough. In disease, increased secretion viscosity and volume, dyskinesia of the cilia, and ineffective cough combine to reduce secretion clearance, leading to increased risk of infection. In obstructive lung disease these conditions are further complicated by early collapse of airways, due to airway compression, which traps both gas and secretions. Techniques have been developed to optimize expiratory flow and promote airway clearance. Directed cough, forced expiratory technique, active cycle of breathing, and autogenic drainage are all more effective than placebo and comparable in therapeutic effects to postural drainage; they require no special equipment or care-provider assistance for routine use. Researchers have suggested that standard chest physical therapy with active cycle of breathing and forced expiratory technique is more effective than chest physical therapy alone. Evidence-based reviews have suggested that, though successful adoption of techniques such as autogenic drainage may require greater control and training, patients with long-term secretion management problems should be taught as many of these techniques as they can master for adoption in their therapeutic routines.

Sulphurous-arsenical-ferruginous (thermal) water inhalations reduce nasal respiratory resistance and improve mucociliary clearance in patients with chronic sinonasal disease: preliminary outcomes.

CONCLUSIONS: In order to confirm these preliminary results, a prospective double-blind study has been instituted in Padova University ENT Section to compare the efficacy of sulphurous-arsenical-ferruginous thermal water nasal irrigations vs isotonic sodium chloride solution nasal irrigations after functional endoscopic sinus surgery for chronic sinusitis. OBJECTIVES: Despite their widespread use, much uncertainty exists about the indications and therapeutic mechanisms of nasal thermal water inhalations in the treatment of sinonasal chronic disease. The aim of the present study was to evaluate the effects of sulphurous-arsenical-ferruginous thermal water inhalations on nasal respiratory flow, mucociliary transport, nasal cytology, and chemo-physics of nasal mucus in a group of consecutive patients with chronic sinonasal disease. PATIENTS AND METHODS: Thirty-seven patients with chronic sinonasal disease underwent a 12-day course of sulphurous-arsenical-ferruginous thermal water warm vapour inhalations (38 degrees C) followed by nasal aerosol of the same thermal water (7 microns micelle). RESULTS: This preliminary study showed that a course of sulphurous-arsenical-ferruginous thermal water inhalations determined a significant improvement in nasal flow and reduction of nasal resistance; a statistically significant reduction of mean mucociliary transport time, from pathologic to physiologic values, has also been shown. Statistical analysis of our data confirmed that the presence of nasal bacteria was significantly reduced by thermal water inhalations.

Effect of needle puncture and electro-acupuncture on mucociliary clearance in anesthetized quails.

BACKGROUND: Acupuncture therapy for obstructive respiratory diseases has been effectively used in clinical practice and the acupuncture points or acupoints of Zhongfu and Tiantu are commonly-used acupoints to treat patients with the diseases. Since the impaired mucociliary clearance is among the most important features of airway inflammation in most obstructive respiratory diseases, the effect of needle puncture and electro-acupuncture at the specific acupoints on tracheal mucociliary clearance was investigated in anesthetized quails. METHODS: Mucociliary transport velocity on tracheal mucosa was measured through observing the optimal pathway, and fucose and protein contents in tracheal lavages were determined with biochemical methods. In the therapeutic group, needle puncture or electro-acupuncture stimulation to the acupoints was applied without or with constant current output in 2 mA and at frequency of 100 Hz for 60 minutes. In the sham group, electro-acupuncture stimulation to Liangmen was applied. RESULTS: Our present experiments demonstrated that the electro-acupuncture stimulation to Zhongfu and Tiantu significantly increased tracheal mucociliary transport velocity and decreased the content of protein in the tracheal lavage, compared with the control group. Moreover, either needle puncture or electro-acupuncture stimulation to Zhongfu and Tiantu significantly reverted the human neutrophil elastase-induced decrease in tracheal mucociliary transport velocity and human neutrophil elastase -induced increase in the contents of fucose and protein in the tracheal lavage, compared with the control group. CONCLUSION: These results suggest that either needle puncture or electro-acupuncture stimulation to the effective acupoints significantly improves both airway mucociliary clearance and the airway surface liquid and that the improvements maybe ascribed to both the special function of the points and the substantial stimulation of electricity.

Multicenter clinical trials on a novel polyherbal formulation in allergic rhinitis.

Allergic rhinitis is the most frequently occurring immunological disorder. It affects men, women and children and represents significant cost in terms of suffering and loss of productivity. Allergy is termed as an excessive reaction to an environmental allergen. Pollen, mold, dust, mite and animal allergens that contact the nasal or eye lining cause sneezing, nasal congestion and itchy, watery, swollen, red eyes. Although a broad spectrum of therapeutic options is available, the treatment of allergic rhinitis appears to be far from satisfactory. A novel polyherbal formulation (PF; Aller-7/NR-A2) comprising seven medicinal herbal extracts was assessed in a multicenter clinical trial involving 545 patients (321 males and 224 females) aged 18-59 years for 12 weeks to evaluate its clinical efficacy in patients suffering from allergic rhinitis. A total of 171 patients participated in double-blind, randomized, placebo-controlled studies in three centers, while 374 patients were included in the open-label studies in 11 centers. The three major symptoms (sneezing, rhinorrhea and nasal congestion) of allergic rhinitis were significantly reduced. Significant improvement was also observed in absolute eosinophil count, mucociliary clearance time, peak expiratory flow rate and peak nasal flow rate. No serious adverse events that warranted cessation of treatment were observed. Minor adverse effects were noted in both the treatment and placebo groups. Thus, this study demonstrates that Aller-7/NR-A2 is well tolerated and efficacious in patients with allergic rhinitis.

Lung tissue eosinophils may be cleared through luminal entry rather than apoptosis: effects of steroid treatment.

Spontaneous or steroid-induced eosinophil apoptosis occurring in vitro has not been demonstrated in lung tissues in vivo. This study examines cell apoptosis in rat lungs using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique and transmission electron microscopy (TEM). After establishing sustained lung edema and eosinophilia by challenge with Sephadex beads intratracheally, budesonide treatment was started intratracheally. Sephadex alone increased the total number of apoptotic cells, which were not efficiently engulfed by macrophages or other cells, in vivo. Yet apoptotic tissue eosinophils were exceedingly rare (1 of 360 TEM-analyzed eosinophils). By contrast, approximately 20% of eosinophils in the airway lumen were apoptotic, and unengulfed. Budesonide promptly inhibited edema but 3 d of steroid treatment were required to reduce the established tissue eosinophilia. Not at any time point did budesonide induce eosinophil apoptosis (0 of 318 TEM-analyzed tissue eosinophils). We conclude that (1) eosinophil apoptosis can occur but is a rare event in vivo in respiratory tract tissues; (2) airway tissue eosinophils, rather than undergoing apoptosis, are eliminated by migration into airway lumen followed by apoptosis and mucociliary clearance; (3) anti-inflammatory steroid treatment may not increase eosinophil apoptosis in vivo nor may it affect the luminal entry of eosinophils; (4) steroids permit elimination of eosinophils into airway lumen and slowly resolve established lung eosinophilia.

beta(2)-adrenergic receptor overexpression increases alveolar fluid clearance and responsiveness to endogenous catecholamines in rats.

beta-Adrenergic agonists accelerate the clearance of alveolar fluid by increasing the expression and activity of epithelial solute transport proteins such as amiloride-sensitive epithelial Na(+) channels (ENaC) and Na,K-ATPases. Here we report that adenoviral-mediated overexpression of a human beta(2)-adrenergic receptor (beta(2)AR) cDNA increases beta(2)AR mRNA, membrane-bound receptor protein expression, and receptor function (procaterol-induced cAMP production) in human lung epithelial cells (A549). Receptor overexpression was associated with increased catecholamine (procaterol)-responsive active Na(+) transport and increased abundance of Na,K-ATPases in the basolateral cell membrane. beta(2)AR gene transfer to the alveolar epithelium of normal rats improved membrane-bound beta(2)AR expression and function and increased levels of ENaC (alpha subunit) abundance and Na,K-ATPases activity in apical and basolateral cell membrane fractions isolated from the peripheral lung, respectively. Alveolar fluid clearance (AFC), an index of active Na(+) transport, in beta(2)AR overexpressing rats was up to 100% greater than sham-infected controls and rats infected with an adenovirus that expresses no cDNA. The addition of the beta(2)AR-specific agonist procaterol to beta(2)AR overexpressing lungs did not increase AFC further. AFC in beta(2)AR overexpressing lungs from adrenalectomized or propranolol-treated rats revealed clearance rates that were the same or less than normal, untreated, sham-infected controls. These experiments indicate that alveolar beta(2)AR overexpression improves beta(2)AR function and maximally upregulates beta-agonist-responsive active Na(+) transport by improving responsiveness to endogenous catecholamines. These studies suggest that upregulation of beta(2)AR function may someday prove useful for the treatment of pulmonary edema.

[Effects of one cycle of inhalation crenotherapy with radioactive fluoridated oligomineral]. / Studio oggettivo degli effetti di un ciclo di crenoterapia inalatoria con acque oligominerali radioattive fluorurate delle Terme di Merano.

The objective of the study was to test the effects of inhalation crenotherapy using the radioactive, fluoridated oligomineral waters from the Merano Spa on both subjects with specific upper respiratory tract phlogosis and normal subjects. The double-blind study was performed on a population of 27 adults of both sexes treated with radioactive-fluoridated water (group A) and 20 subjects, suffering from the same chronic catarrh pathology, selected with the same criteria but treated with inhalation of steam and an aerosol using drinking water from the municipal water supply (group C). In addition, a group of 13 subjects--which in terms of age and sex were statistically comparable to groups A and C but who did not show any signs of acute or chronic upper respiratory tract pathologies (group B) were also treated with the radioactive-fluoridated waters. All subjects included in the study underwent the following tests before and after the cycle of crenotherapy: Objective E.N.T. examination. Computerized Active Anterior Rhinomanometry. Detection of the ciliary mucous transport (CMT) time. Nasal cytology. Physical and immunochemical examination of the nasal mucous. The results of this study--seen in the trend in some parameters monitored both before and after the cycle of crenotherapy using Merano Spa water--clearly show that that the crenotherapy studied had an effect on aspecific chronic phlogosis of the upper respiratory tract. In fact, among other things, group A showed decreased nasal resistance, increased nasal respiratory flow, normalized mucociliary transport, decreased bacterial flora and an increased number of plasma cells in the rhinocytogram. In addition there was an increase in the following values in the nasal mucous: Albumin, non-secretory Immunoglobulin and the secretory portion of secretory Immunoglobulin A. None of these variations are seen in the results from the control group treated with municipal drinking water. After treatment with Merano spa water, the pathology-free subjects showed variations in the parameters in line with those found for group A. This biological reality can most likely be attributed to the favorable response of the respiratory mucosa, promoting anti-infection defenses.

[Effects of sulphur-arsenic-ferrous water treatment on specific chronic phloglosis of the upper respiratory tract]. / Studio sperimentale degli effetti di un ciclo di trattamento con acque solfato-arsenicali-ferruginose su flogosi croniche aspecifiche delle vie aeree superiori.

The aim of the present study was to demonstrate the therapeutic effect sulphurous-arsenical-ferruginous waters from had on aspecific phlogosis of the upper respiratory tract (URT). This double-blind study involved treating 37 adults of both sexes with sulphurous-arsenical-ferrignous water (group A) and another 14 subjects, again suffering from the same aspecific, chronic catarrhal disorder and selected with the same criteria, with the aerosol vapor inhalation of drinking water from the city mains (group B). All subjects included in the study underwent the following tests both before and after the cycle of crenotherapy: Objective E.N.T. examination Anterior Active Computerized Rhinomanometry (AACR) Mucociliary transport time (MTT) Nasal cytology Physical and immunochemical examination of the nasal mucous. The post crenotherapy variations achieved indicate that the sulphurous-ferruginous waters have a beneficial therapeutic effect: indeed, the mucosa was able to perform its complex functions, particularly specific and aspecific defense of the organism. In fact, among other things, group A showed decreased resistance and increased nasal respiratory flow, normalized of mucociliary transport, decreased bacterial layer and increased plasma cells in the rhinocytogram, and an increase in albumin, non secretory immunoglobulin and the secretory portion of secretory immunoglobulin A in the nasal mucosa. None of these variations--many of which were statistically significant--were seen in the controls group treated with drinking water from the public mains.

Sputum rheology changes in cystic fibrosis lung disease following two different types of physiotherapy: flutter vs autogenic drainage.

OBJECTIVE: The aim of the present study was to investigate the efficacy of two frequently used physiotherapies (PTs) for the removal of bronchial secretions in cystic fibrosis (CF) lung disease: autogenic drainage (AD) and the Flutter (Desitin in Germany). AD is believed to improve mucus clearance from peripheral to central airways due to airway caliber changes in combination with a special breathing technique. The Flutter is an easy-to-use physiotherapy device based on oscillations of a steel ball during expiration through a pipe-type device. MATERIALS AND METHODS: To evaluate the acute and chronic physiotherapy effects of these two techniques, 14 CF patients underwent either twice daily AD or Flutter treatment for 4 consecutive weeks in a randomized crossover design. Prior to each therapy interval, for a 1-week wash-out period, no PT was administered, but patients continued regular medication. At the beginning and end of each 4-week interval, pulmonary function was measured before and after an acute 30-min therapy. At the end of the PT session, sputum was collected, weighed, and deep frozen until analyzed. The viscoelasticity of the sputum was evaluated using a magnetic microrheometer. RESULTS: No significant changes were noted for FVC, FEV1, or sputum volume throughout the study. Sputum viscoelasticity (rigidity index), however, was significantly lower (p<0.01) after therapy with the Flutter in comparison with AD, predicting improvements in mucociliary and cough clearability of the secretions. In a companion in vitro experiment, oscillations generated by passing humidified air over CF sputum lining an acrylic tube connected to a Flutter de-ice were found to decrease sputum elasticity, as measured by a filancemeter. These findings suggest that applied oscillations are capable of decreasing mucus viscoelasticity within the airways at frequencies and amplitudes achievable with the Flutter device, and provide direct evidence that PT can reduce the viscoelasticity of sputum.

The herbal medicine, sairei-to, prevents endotoxin-induced otitis media with effusion in the guinea pig.

With current pharmacotherapy, otitis media with effusion (OME) is often recurrent and even develops to become chronic. There is now considerable experimental and clinical evidence that the cilia in the tubotympanum play an important part in the prevention of OME. A herbal medicine, sairei-to, has been shown to stimulate the ciliary activity in vitro, and oral administration of the medicine also stimulated the ciliary activity in the tubotympanum rather than physiological states. This study was designed to investigate whether oral administration of sairei-to could prevent experimental OME in the guinea pig. A total of 120 guinea pigs were used. The control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 120 and 600 mg/kg of sairei-to for 14 successive days, respectively. The saline-control group, the low-dosage group and the high-dosage group were then treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 micrograms/ml) derived from Klebsiella pneumoniae. All 10 animals from the 4 groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions in the low-dosage and the high-dosage groups was somewhat reduced compared with the saline-control group. The ciliary activity in the tubotympanum was significantly reduced in the saline-control and low-dosage groups compared with the normal-control group. By contrast, the magnitude of reduction in ciliary activity was much smaller in the high-dosage group. The ciliary activity especially in the Eustachian tube and the middle ear close to the tympanic orifice at 3 and 7 days in the high-dosage group was not significantly different from that in the normal-control group. Mucociliary clearance time in the high-dosage group was not different from that in the normal-control group throughout the observation period. The groups treated with sairei-to, especially the high-dosage group, exhibited much milder pathological changes in the tubotympanum than did the saline-control group. In conclusion, clinical application of sairei-to could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially OME-prone individuals.

[Nasal mucociliary transport time and ciliary beat frequency in healthy probands and patients with sinusitis]. / Nasale mukoziliare Transportzeit und ziliare Schlagfrequenz bei Gesunden und Sinusitispatienten.

The mucociliary system is an important defence mechanism of the respiratory tract. It depends on the interaction between cilia and mucus. To evaluate the value of the saccharin test and a photoelectrical in-vitro method for measurement of ciliary beat frequency for clinical routine diagnosis, we studied twenty patients suffering from acute sinusitis (aged 19-64) and twenty healthy non-smokers (aged 19-50). The nasal mucociliary transport time of saccharin was significantly higher (p < or = 0.01) and the ciliary beat frequency was significantly lower (p < or = 0.001) in patients with acute sinusitis, compared to normals. There was no correlation between nasal mucociliary transport time and ciliary beat frequency in patients with acute sinusitis (r = 0.21) and in healthy non-smokers (r = -0.37). Nasal mucociliary transport time of saccharin and photoelectrical in-vitro method for measurement of ciliary beat frequency measure different aspects of the mucociliary system. They are complementary. Both methods can be carried out together in routine diagnosis.