Dinámica y patología del barrido mucociliar como mecanismo defensivo del pulmón y alternativas farmacológicas de tratamiento / Mucociliary clearance system in lung defense

The first line of defense to maintain the sterility of the intrapulmonary airways is the mucociliary clearance system. This rapidly responding, non-specific, immune defensive system is challenged by approximately 12,000 liters of air filtered by the lungs each day, containing millions of particles like spores, environmental and eventually toxic pollutants. The main components of this system are the floating mucus "blanket", the underlying mucus propelling cilia with periciliary fluid, and the airway epithelium with secretory and ciliated type of cells. The fine and coordinated regulation of these three components is critical for an effective performance. Deregulation resulting from continuous insults, inherited ion channel disease, infections or abnormal immune response may lead to mucus alterations, goblet cell hyperplasia and metaplasia, airway obstruction, air trapping and chronic lung disease. Options for treatment are limited. Understanding this system may reveal new targets for treatment of lung disease.

Antitussive and mucoactive drugs

Cough is the most frequent complaint from medical patients even though coughing is a protective reflex. The principle of relief from a cough is treatment of its underlying disease. However, when the treatment of the cause of coughing is not effective, cough suppression therapy just to relieve the symptom may be attempted. Antitussives and mucoactive drugs are used for this purpose. Unfortunately, the currently available agents are not consistently effective and frequently have intolerable side effects. Therefore, understanding the side effects and mechanism of action of these agents is definitely needed. This review provides a summary of the currently available antitussives and mucoactives.

Produção e comercialização de fitoterápicos à base de Hedera helix: avaliação comparativa dos produtos disponíveis no Brasil / Production and marketing of Hedera helix-based phytotherapeutic products: comparative assessment of the products available in Brazil

O mercado brasileiro de fitoterápicos apresenta diversos produtos broncodilatadores e expectorantes produzidos com extratos da espécie hera (Hedera helix L. - Araliaceae), os quais apresentam distintas composições em termos de quantidade de extrato seco e de marcador por ml. Visando contribuir ao entendimento dessas diferenças, realizou-se levantamento da literatura clínica sobre a espécie com foco nos aspectos de concentração de extratos e quantidade de marcadores. Verificou-se existirem mundialmente três diferentes formatos comerciais de extratos de hera, preparados com relação droga-extrato de 3-6:1, 5-7,5:1 e 4-8:1, gerando diferentes teores de marcador por cento. Os dois primeiros formatos estão presentes no mercado brasileiro, apresentam base clínica eficaz e segura, demonstrando que a espécie em questão mostra faixa variável de ação. O estudo multicêntrico de maior evidência clínica foi realizado por Fazio e colaboradores (2009), utilizando produto com concentração de marcadores que somente são fornecidas, no Brasil, pelos fitoterápicos de formulação do tipo 5-7,5:1, enquanto produtos no formato de formulação 3-6:1 apresenta teores abaixo do mínimo utilizado nesse estudo multicêntrico. O perfil de segurança dos vários tipos de produtos à base de Hedera helix é muito bem estabelecido, com mínimas ocorrências de efeitos adversos, basicamente gastrointestinais.

Tosse: neurofisiologia, métodos de pesquisa, terapia farmacológica e fonoaudiológica / Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology

Introdução: A tosse é o sintoma respiratório mais comum em crianças e adultos. Objetivo: Apresentar uma revisão sobre a neurofisiologia e os métodos para estudo do reflexo da tosse, bem como a farmacoterapia e terapia fonoaudiológica da tosse, baseada nos trabalhos publicados entre 2005 e 2010 e indexados nas bases Medline, Lilacs e Biblioteca Cochrane sob os unitermos "tosse" ou "antitussígenos". Síntese dos dados: O reflexo da tosse envolve ativação de múltiplos receptores vagais nas vias aéreas e de projeções neurais do núcleo do trato solitário para outras estruturas do sistema nervoso central. Técnicas experimentais permitem estudar o reflexo da tosse ao nível celular e molecular para desenvolver novos agentes antitussígenos. Não há evidências de que antitussígenos isentos de prescrição médica tenham eficácia superior à do placebo para o alívio da tosse. A terapia fonoaudiológica pode beneficiar pacientes com tosse crônica refratária ao tratamento farmacológico, sobretudo quando coexiste movimento paradoxal das pregas vocais. Comentários Finais: A abordagem multidisciplinar tem papel fundamental no diagnóstico etiológico e tratamento da tosse. O otorrinolaringologista deve informar os pacientes sobre os riscos dos antitussígenos de venda livre a fim de prevenir intoxicações e efeitos adversos, especialmente em crianças...

Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children...

Pharmacokinetics and Tolerability Evaluation of Fudosteine after Oral Administration in Healthy Korean Volunteers

BACKGROUND: Fudosteine, (-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid, is a cysteine derivative that was approved in Japan, as a new mucoactive agent. The aim of this study was to evaluate the tolerability and pharmacokinetics (PK) of fudosteine in healthy Korean subjects. METHODS: A randomized, open-label, parallel, escalating single-dose study was conducted in 16 healthy Korean male subjects. The subjects were allocated to single-dose groups of 400 or 800 mg. Serial blood samples for PK analysis were collected immediately prior and after dosing up to 24 hours, and plasma concentrations were determined by high performance liquid chromatography (HPLC). Safety profiles were evaluated by monitoring adverse events and clinical evaluations throughout the study. RESULTS: Median time to peak concentration (Tmax) of both dosing group were around 0.5 hours and half-life (t1/2) were around 3 hours. Mean peak concentration (Cmax) of 400 mg and 800 mg dosing group were 10.8 and 21.5 microg/mL and the mean area under the plasma concentration versus time curve from the dosing time to infinity (AUCinf) were 26.8 and 55.0 microg.h/mL, respectively. Mean dose-normalized Cmax were 0.0271 and 0.0269 microg/mL/mg (P=0.923), respectively and dose-normalized AUCinf were 0.0669 and 0.0688 microg.hr/mL/mg (P=0.093), respectively. Fudosteine was well tolerated without any serious adverse events or clinical laboratory abnormalities. CONCLUSION: This study showed that fudosteine has a linear PK property and is well tolerated within 800 mg in healthy Korean volunteers.

Clinical significance of inhaling ambroxol hydrochloride in airway inflammation in elderly patients with chronic obstructive pulmonary disease / 中华老年医学杂志

Objective 1.To establish an improved method by inhaling hyperosmotic saline and mucosolvan ampoule and to observe the security and validity in elderly patients with chronic obstructive pulmonary disease(COPD).2.To observe the changes of cell component and soluble substance in the induced sputum of the elderly patients with COPD at their acute and stable stage,and explore the role of these substances in airway inflammation. Methods 1.40 elderly patients with COPD who were at their acute stage were stochastically divided into two groups,20 patients each,who inhaled hyperosmotic saline(3%)(group A)and hyperosmotie saline(3%)plus ambroxol hydrochloride(group B).We compared their electrocardiogram before and after inhalation,lung function,saturation of oxygen in artery,cell component,inflammatory factors in sputum and validity of inducing sputum.2.The cell component,inflammatory factors and the lung function of the patients in group B were determined at their acute and stable stage. Results 1.55.0% of the patients in group A felt uncomfortable.and 2 of them had excessive bronchial irritability so not undergoing sputum inducement.However,side effects were found in only 5 patients of the group B.Side effects in the group B were lower than those in hyperosmotic saline group(P＜0.05).Before and after the experiment,electrocardiogram of the patients in the two groups had no statistical difference(P＞0.05).It was the same as lung function and oxygenic saturation.Cell component and inflammatory faetors in the sputum of the two groups had no statistical difference(P＞0.05).2.In group B,the total cells,monoeyte,neutrophil,IL-8 and TNF-αof the patients at their acute stage were(3.4 5±0.52)×108/L,(38.8±4.3)%,(30.8±3.1)%,(316.75±43.14)ng/L,(39.4±4.58)ng/L.respectively.And those at their stable stage were(2.94±0.57)×108/L,(29.1±6.1)%,(28.2±4.2)%,(170.00±25.70)ng/L,(20.60±5.10)ng/L,respectively.The total cells,monocyte,neutrophils,IL-8 and TNF-α in acute and stable stage of the patients had statistical significance(P＜0.05).There was a negative correlation of the total cells,monocyte,neutrophil,IL-8,TNF-αwith the degree of the disease in group B at acute and stable stage. Conclusions The results suggest that inhaling ambroxol hydrodiloride is a practical,safe and effective method,for clarifying the mechanism of airway inflammation in elderly patients with COPD.

The Impact of Different Endotracheal Suction Methods on Respiratory Function: Normal Saline with Chest Vibration vs Normal Saline with Expectorant Mixture / 성인간호학회지

PURPOSE: Regarding the respiratory function of patients with an artificial airway, this study compared the effects between normal saline with chest vibration and normal saline with expectorant mixture, administered before endotracheal suction. METHODS: The study was conducted in the ICUs of one university hospital located in Incheon. The experimental group I received normal saline with chest vibration administered before endotracheal suction while the experimental group II received normal saline with expectorant mixture administered before endotracheal suction. For respiratory function, PaO2, PaCO2, and O2 saturation were measured by ABGA at 3 minutes after endotracheal suction for both pre-test and post-test. RESULTS: The two groups were not different significantly regarding PaO2 level and O2 saturation after the treatments, while, the experimental group II had lower PaCO2 level than the experimental group I after the treatments (t = 2.075, p = .042). For experimental group II, post-test score of PaCO2 level was significantly lower than that of the pre-test score (t = 1.842, p = .075). CONCLUSION: The administration of normal saline with expectorant mixture before endotracheal suction reduced PaCO2 level and improved the respiratory function.

The Impact of Different Endotracheal Suction Methods on Respiratory Function: Normal Saline with Chest Vibration vs Normal Saline with Expectorant Mixture / 성인간호학회지

PURPOSE: Regarding the respiratory function of patients with an artificial airway, this study compared the effects between normal saline with chest vibration and normal saline with expectorant mixture, administered before endotracheal suction. METHODS: The study was conducted in the ICUs of one university hospital located in Incheon. The experimental group I received normal saline with chest vibration administered before endotracheal suction while the experimental group II received normal saline with expectorant mixture administered before endotracheal suction. For respiratory function, PaO2, PaCO2, and O2 saturation were measured by ABGA at 3 minutes after endotracheal suction for both pre-test and post-test. RESULTS: The two groups were not different significantly regarding PaO2 level and O2 saturation after the treatments, while, the experimental group II had lower PaCO2 level than the experimental group I after the treatments (t = 2.075, p = .042). For experimental group II, post-test score of PaCO2 level was significantly lower than that of the pre-test score (t = 1.842, p = .075). CONCLUSION: The administration of normal saline with expectorant mixture before endotracheal suction reduced PaCO2 level and improved the respiratory function.

Effects of Yiqi Huoxue Tablet on Expression of Platelet Membrane Adhesion Molecules in Rats with Cerebral Infarction / 广州中医药大学学报

[Objective] To investigate the effects of Yiqi Huoxue Tablet (YHT, mainly composed of Radix Angelicae Sinensis, Herba Leonuri, Rhizoma Chuanxiong , Radix Astragali ) on expression of platelet membrane adhesion molecules (PMAM) in whole blood of rats with cerebral infarction. [Methods] Flow cytometry was used to detect the expression of PMAM (CD

Effect of Naohuandan Capsule in Treating Mild and Moderate Cases of Vascular Dementia / 广州中医药大学学报

To observe the therapeutic effect of Naohuandan Capsule (mainly composed of Radix Ginseng, Radix Rehmanniae Preparata,etc.) in treating mild and moderate cases of vascular dementia (VD).Forty five cases of VD, which are subjected to the diagnostic standard of American Association of Psychiatry (DSM Ⅳ), were randomly allocated to two groups for a 3-month treatment course. Group A (n=22) was treated with Naohuandan Capsule and Group B (n=23) with Naofukang Tablet. Therapeutic effect was evaluated by scoring of mini-mental state examination (MMSE) and activity of daily living (ADL) and serum levels of estradiol (E 2) and testosterone (T) were also observed.Scores of MMSE and ADL were increased, E 2 and T levels were elevated and the ratio of E 2/T was decreased in Group A(P0 05). [Conclusion]Naohuandan Capsule has a definite effect in preventing and treating VD and its mechanism may be related to the increase of E 2 and T levels, decrease of E 2/T ratio and the regulation of neuroendocrine function.

Effects of Blood-Circulation Promoting and Phlegm Removing Treatment on Mitochondria membrane in Spontaneous Hypertensive Rats / 广州中医药大学学报

Objective To explore the effects of blood-circulation promoting and phlegm removing treatment on the structure, activity of Ca 2+ -Mg 2+ ATPase and malondialdehyde(MDA) content of mitochondria membrane in spontaneous hypertensive rats (SHR). Methods Spontaneous hypertensive rats (SHR) were classified into 14-week-old model group(Group C),28-week-old model group(Group D) and treatment group (treated with blood-circulation promoting and phlegm removing Chinese herbal medicine,Group E).Normal Wistar rats 14 weeks old (Group A)and 28 weeks old(Group B) served as the controls.The structure of myocardial mitochondria membrane were analyzed quantitatively by transmission electron microscope,and the activity of Ca 2+ -Mg 2+ ATPase and MDA content were also detected. Results Specific surface area of mitochondria was smaller, the activity of Ca 2+ -Mg 2+ ATPase was lower and MDA content was higher in SHR than the controls.MDA content increased as the duration of disease prolonged. Chinese herbal medicine could counteract the above changes. Conclusion Blood-circulation promoting and phlegm removing herbs can partially counteract the progress of left ventricular hypertrophy in SHR.

A Clinical Study of Lipi Huatan Jiangzhi Tablet for Hyperlipemia / 广州中医药大学学报

To investigate the therapeutic effects of Lipi Huatan Jiangzhi Tablet(LHJT),80 cases of hyperlipenda were landomly allocated to LHJT group(50) and lypanthy group(30) and single-blindedtrial was applied.Blood lipids(total cholesterol,triglyceride,high density lipoprotein,apoprotein A andapoprotein B),blood theology and free radicals(lipid peroxide, superotide dismutase and glutathionesuperokidase) were observed.The results showed that the regulatory effect on lipid medslism in LHJTgroup was better and more stable; blood theology, free radicals and the main symptoms were more improved as comapared with lypanthy group. Meanwhile,the total effective rate of LHJT for patients withspleen-deficiency and phlegm-stagnation syndrome was higher than that with other TCM syndromes(P

Effect of Jiazhongfang on Benign Nontoxic Goiter / 广州中医药大学学报

0.05 ). The total effective rate was 89.29 % and 62.50 % in Group A and Group B respectively, the differences being significant ( P