Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1ß (IL-1ß) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1ß. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

L'utilisation du monoxyde d'azote inhalé chez les nouveau-nés.

Le monoxyde d'azote inhalé (NOi), un vasodilatateur pulmonaire sélectif, est utilisé pour le traitement des nouveau-nés en insuffisance respiratoire hypoxémique (IRH) associée à une hypertension pulmonaire persistante du nouveau-né. Idéalement, il doit commencer à être administré après la confirmation échocardiographique de ce type d'hypertension. L'utilisation de NOi est recommandée chez les nouveau-nés peu prématurés ou à terme chez qui survient une IRH malgré des stratégies d'oxygénation ou de ventilation optimales. Cependant, il n'est pas recommandé d'y recourir systématiquement chez les nouveau-nés prématurés sous assistance respiratoire. On peut l'envisager comme traitement de secours chez les nouveau-nés prématurés en IRH précoce associée à une rupture prolongée des membranes ou à un oligoamnios, ou en IRH tardive en cas d'hypertension pulmonaire liée à une dysplasie bronchopulmonaire et accompagnée d'une insuffisance ventriculaire droite marquée. On peut aussi l'envisager chez les nouveau-nés atteints d'une hernie diaphragmatique congénitale qui présentent une IRH persistante, malgré un recrutement pulmonaire optimal, des signes échocardiographiques d'hypertension pulmonaire suprasystémique et un fonctionnement ventriculaire gauche approprié.

Definition of internal target volumes based on planar X-ray fluoroscopic images for lung and hepatic stereotactic body radiation therapy. Comparison to inhale/exhale CT technique.

PURPOSE: To compare tumor motion amplitudes measured with 2D fluoroscopic images (FI) and with an inhale/exhale CT (IECT) technique MATERIALS AND METHODS: Tumor motion of 52 patients (39 lung patients and 13 liver patients) was obtained with both FI and IECT. For FI, tumor detection and tracking was performed by means of a software developed by the authors. Motion amplitude and, thus, internal target volume (ITV), were defined to cover the positions where the tumor spends 95% of the time. The algorithm was validated against two different respiratory motion phantoms. Motion amplitude in IECT was defined as the difference in the position of the centroid of the gross tumor volume in the image sets of both treatments. RESULTS: Important differences exist when defining ITVs with FI and IECT. Overall, differences larger than 5 mm were obtained for 49%, 31%, and 9.6% of the patients in Superior-Inferior (SI), Anterior-Posterior (AP), and Lateral (LAT) directions, respectively. For tumor location, larger differences were found for tumors in the liver (73.6% SI, 27.3% AP, and 6.7% in LAT had differences larger than 5 mm), while tumors in the upper lobe benefitted less using FI (differences larger than 5 mm were only present in 27.6% (SI), 36.7% (AP), and 0% (LAT) of the patients). CONCLUSIONS: Use of FI with the linac built-in CBCT system is feasible for ITV definition. Large differences between motion amplitudes detected with FI and IECT methods were found. The method presented in this work based on FI could represent an improvement in ITV definition compared to the method based on IECT due to FI permits tumor motion acquisition in a more realistic situation than IECT.

The potential of Atorvastatin for chronic lung diseases therapy.

Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase thus leading to a reduction in cholesterol synthesis. It has recently been demonstrated that ATO has different pharmacological actions, which are unrelated to its lipid-lowering effects and has the ability to treat chronic airway diseases. This paper reviews the potential of ATO as an anti-inflammatory, antioxidant, and anti-proliferative agent after oral or inhaled administration. This paper discusses the advantages and disadvantages of using ATO under conditions associated with those found in the airways. This treatment could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases.

In vitro killing of drug susceptible and multidrug resistant bacteria by amikacin considering pulmonary drug concentrations based on an inhaled formulation.

Nosocomial infections with drug resistant bacteria impact morbidity and mortality, length of therapy and stay and the overall cost of treatment. Key pathogens with ventilator associated pneumonia may be drug-susceptible or multi-drug resistant and inhaled amikacin has been investigated as an adjunctive therapy option. High pulmonary drug concentrations (epithelial lining fluid [ELF]) along with minimal systemic toxicity is seen as an advantage to inhaled formulations. In vitro killing of bacteria using clinically relevant drug concentrations provide insight on bug-drug interactions. The aim of this study was to measure killing of clinical isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus using the minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and median (976 µg/ml) ELF drug concentration for amikacin. Overall killing took longer at the MIC drug concentration and was inconsistent amongst the pathogens tested with the percentage of bacteria killed following 180 min of drug exposure ranging from growth in the presence of the drug to 95% kill. At the MPC drug concentrations, killing ranged from 55-88% for all pathogens following 30 min of drug exposure and increased to 99-100% following 180 min of drug exposure. At the ELF amikacin tested, killing was 81-100% following 20 min and 94-100% by 30 min of drug exposure. Rapid killing against MDR respiratory pathogens by amikacin ELF drug concentrations is encouraging.

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH-induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half-life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH-induced RVF.

Predicting Inhaled Drug Dose Generated by Mesh Nebulizers.

Background: The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. Methods: An in vitro model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns (n = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the ex vivo study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. Results: The in vitro model showed that the inspiratory time to total respiratory cycle time (Ti/Ttotal; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The ex vivo model showed that Ti/Ttotal was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the ex vivo model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. Conclusions: The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.

[Cushing's syndrome with inhaled corticosteroid: Drug interactions to avoid]. / Syndrome de Cushing sous fluticasone inhalée : interactions médicamenteuses à éviter.

Cushing's syndrome is an iatrogenic event occurring during co-administration of inhaled corticosteroids and potent inhibitors of P450 cytochromes. We report the clinical case of a 29-year-old woman with a past history of asthma treated with inhaled fluticasone propionate (FP), chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) treated with itraconazole (ITZ), and Mycobacterium xenopi infection treated with moxifloxacin (MXF), ethambutol (EMB) and clarithromycin (CLR). Four months after initiation of antibiotic and antifungal medication, the patient contracted Cushing's syndrome. Its etiology consisted in interaction between FP, ITZ and CLR, which led to pronouncedly increased corticosteroid concentrations in circulating plasma cells. Following on the one hand cessation of FP and ITZ and on the other hand hydrocortisone supplementation, evolution was favorable. Several cases of iatrogenic Cushing's syndrome induced by co-administration of FP and potent CYP3A4 inhibitors have been reported in the literature. If possible, FP should be avoided in patients being treated with CYP3A4 inhibitors. Due to its differing physicochemical properties, beclometasone may be considered as the safest therapeutic alternative.

Dose-related effects of inhaled essential oils on behavioural measures of anxiety and depression and biomarkers of oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EOs) are extracts of organic, volatile metabolites of plants that are typically oily liquids at ambient temperatures. Inhalation of EOs can regulate brain health and functions associated with mood and neurodegeneration, reflecting their bioavailability to brain. The aim was to identify physicochemical properties that influenced EO volatility and pathways of brain uptake by inhalation. MATERIALS AND METHODS: Dose-dependency of effects, determined as: total EO intake (µg/g bodyweight-BW), and rate of EO intake (µg/hr/g-BW), was determined by meta-analysis of data from animal studies (10 studies, 12 EOs), measuring effects on anxiety, depression and selected biomarkers of oxidative stress and inflammation (OSI). RESULTS: Results demonstrated benefits on animal behavior at EO intakes of 1-100 µg/g BW and 1-10 µg/hr/g BW (Elevated Plus Maze and Forced Swimming tests) and <100 µg/g BW and 10-100 g/hr/g BW (Marble Burying). EOs regulated OSI biomarkers at intakes of 10-100 µg/g BW and 1-10 µg/h/g BW, and a dose-dependent elevation of dopamine at >1000 µg/g BW and 100-1000 µg/hr/g BW. CONCLUSION: The results support that EO 'aromatherapy' can promote dose-dependent regulation of anxiety, depression and OSI and that efficacy requires optimization of dose.

Preferences and Inhalation Techniques for Inhaler Devices Used by Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Inhaler technique and patient preferences are often overlooked when selecting maintenance treatments for patients with chronic obstructive pulmonary disease (COPD), but are important issues in ensuring drug efficacy and patient adherence. Few data on these issues are available for new inhalation devices. OBJECTIVES: To evaluate the inhalation techniques for the HandiHaler®, Breezhaler®, Genuair®, and Respimat® inhalation devices, and patient preferences for the three latter inhalers that were recently developed. METHODS: A prospective two-center cross-sectional study of COPD patients was conducted. The patients were required to be current HandiHaler users who had not previously used the new inhalers (Breezhaler, Genuair, Respimat). The patients were given the new devices and asked to identify the one they preferred before and after using the inhaler. Each patient tried the HandiHaler and two devices out of the three new inhalers: one preferred by the patient and one imposed by the investigator. Their inhalation technique was evaluated using an assessment checklist. A logistic regression model was used to determine which device was used with the fewest errors. RESULTS: Of the 98 patients who completed the study, 57.1% (95% CI: 47.4-66.9) had an adequate HandiHaler technique. There was no difference between the proportions of patients with an adequate Breezhaler and Genuair inhalation technique (aOR 1.08, 95% CI: 0.51-2.30), but 62% fewer patients using Respimat had an adequate technique than those using Genuair (aOR for adequate technique 0.38, 95% CI: 0.18-0.82). There were no significant differences in the initial patient preferences for the three new inhalers, and no association between the patient's preference and an adequate inhaler technique. CONCLUSION: Inhalation techniques were suboptimal and varied between inhalers. The arrival of new inhalers is an opportunity to reassess patient techniques and preferences. Further studies should also explore the association between the inhaler preferences and treatment adherence of patients.

[Effect of Different Concentrations of Moxa-smoke on Lung Function and TNF-α and IL-1 ß Levels in Serum and Lung Tissues in Normal Rats].

OBJECTIVE: To study the effect of moxa-smoke inhaling on the respiratory system, so as to provide experimental data and theoretical basis for evaluating the safety of moxa-smoke inhaling during moxibustion treatment. METHODS: A total of 48 SD rats were randomized into control, low, medium and high moxa-smoke-concentration groups (n＝12 in each group). The low, medium and high concentrations of smoke were controlled in (0.11±0.05) mg/m3, (0.23±0.05) mg/m3 and (0.53±0.05) mg/m3 respectively in each of 3 glass boxes (with reference to the level of PM 2.5). The smoking was conducted 4 hours each time, twice a day for 100 days. The normal group did not receive any moxa-smoke inhaling. The histopathological changes of lung and bronchial tissues were detected by H．E. stainning, and the contents of TNF-α and IL-1 ß of plasma, bronchoalveolar la-vage fluid (BALF) and lung tissue detected by ELISA. The levels of forced vital capacity (FVC), forced expiratory volume (FEV), FEV 0.3/FVC (0.3＝ the 0.3rd second), maximal mid-expiratory flow rate(MMEF), peak expiratory flow(PEF) were detected by animal pulmonary function analysis system. RESULTS: After 100 days' moxa-smoke inhaling, the contents of TNF-α in the plasma, BALF and lung tissues and IL-1 ß in the lung tissue of the low, medium and high concentration moxa-smoke groups, and IL-1 ß in the plasma and BALF of the medium and high concentration groups were significantly increased relevant to the control group (P<0.05, P<0.01). H．E. stain showed various inflammatory changes in the lungs and trachea tissues, including obvious fusion of pulmonary alveoli, lymphocyte infiltration, increase of capillary permeability, red blood cell exudation, etc. in the high concentration group, these situations were milder in the medium concentration group and were not obvious in the low concentration group. Compared with the control group, there were no significant changes in the FVC, FEV, FEV 0.3/FVC, MMEF and PEF of lung function in the three concentration groups (P> 0.05)．. CONCLUSION: Long term inhalation of high concentration of moxa-smoke may lead to inflammatory injury in the lung and bronchial tissues but has no significant effect on the respiratory function in rats. Nevertheless, a good air-ventilation during moxibustion in a treatment room is necessary.

[Theoretical and practical assessment of Lille general practice and pharmacy students' knowledge about use of inhaler devices for asthma control]. / Évaluation théorique et pratique de la connaissance d'utilisation des dispositifs inhalés dans l'asthme chez les internes en médecine générale et les étudiants en pharmacie de Lille.

INTRODUCTION: Asthma is a potentially serious chronic respiratory disease impacting patients quality of life. Satisfactory control requires proper use of inhaled devices. This study assesses general medical residents and pharmacy students knowledge about proper use of inhaled asthma devices. MATERIALS AND METHODS: We evaluated knowledge of 43 general practice students and 43 pharmacy students in Lille for three inhaler devices (metered-dose inhaler, Turbuhaler® and Diskus®) during individual interviews. Students were assessed on 8 proper use criterias for each device. RESULTS: General practice and pharmacy students are unfamiliar with proper use of inhaler devices. However, pharmacy students get better average scores than general practice students for all devices included in this study: 6.3/8 respected criterias against 5/8 for metered-dose inhaler; 5.3/8 against 3.2/8 for Turbuhaler®; and 6/8 against 4.3/8 for Diskus®. Pharmacy students more frequently perform a demonstration of proper use to patients when a device is first prescribed or when a prescription is renewed; general practice students more frequently ask patients themselves to perform a demonstration of proper use. CONCLUSION: Introducing trainings workshops for inhaler devices to pharmacy and general practice students appears appropriate in order to promote therapeutic patient education, to increase asthma control and better patients life quality.

Can we improve clinical outcomes in patients with pneumonia treated with antibiotics in the intensive care unit?

INTRODUCTION: Pneumonia in the intensive care unit (ICU) is associated with high morbidity, mortality and healthcare costs. However, treatment outcomes with conventional intravenous (IV) antibiotics remain suboptimal, and there is an urgent need for improved therapy options. AREAS COVERED: We review how clinical outcomes in patients with pneumonia treated in the ICU could be improved; we discuss the importance of choosing appropriate outcome measures in clinical trials, highlight the current suboptimal outcomes in patients with pneumonia, and outline potential solutions. We have included key studies and papers based on our clinical expertise, therefore a systematic literature review was not conducted. Expert commentary: Reasons for poor outcomes in patients with nosocomial pneumonia in the ICU include inappropriate initial therapy, increasing bacterial resistance and the complexities of IV dosing in critically ill patients. Robust clinical trial endpoints are needed to enable an accurate assessment of the success of new treatment approaches, but progress in this field has been slow. In addition, only very few new antimicrobials are currently in development for nosocomial pneumonia; two potential alternative solutions to improve outcomes could therefore include the optimization of pharmacokinetic/pharmacodynamics (PK/PD) and dosing of existing therapies, and the refinement of antimicrobial delivery by inhalation.

[Nasally delivered drugs (corticosteroids and vaccines), ultra long-acting bronchodilators and inhaled therapies in an animal model]. / Médicaments administrés par voie nasale (corticoïdes et vaccins), bronchodilatateurs de très longue durée d'action et aérosolthérapie dans un modèle animal.

Inhaled therapies are widely prescribed. Several aspects of these treatments were considered during the 4th meeting of the aerosol therapy workgroup (GAT) of the French-speaking respiratory society (Société de pneumologie de langue française [SPLF]). In this report, will be detailed the medications delivered by the nasal route, particularly corticosteroids and vaccines as well as the ultra long-acting beta2-agonists, and inhaled therapies for asthma due to allergy to cat dander.

The effect of loaded deep inhale training on mild and moderate COPD smokers.

OBJECTIVE: To research the therapeutic effect of loaded deep inhale training on mild and moderate COPD smokers. DESIGN: 30 mild and moderate COPD smokers were divided into the observation group and the control group at random. The observation group underwent loaded deep inhale training in the morning and in the evening twice for 30 minutes each time for 3 months. The control group did regular aerobics like jogging twice a day for 30 minutes as well for 3 months. The power of respiratory muscles and pulmonary function parameters of each group were measured and compared before and three months after the training. RESULTS: After 3 months of hard training, pulmonary function parameters of the observation group was impressively improved compared with the control group and before training. CONCLUSIONS: Loaded deep inhale exercise has a remarkable effect on improving pulmonary function of mild and moderate COPD.

The influence factor analysis of retinopathy of prematurity / 天津医药

Objective To investigate the incidence of retinopathy of prematurity (ROP) and analyse the associated risk factors of the severe ROP. Methods A total of 703 preterm infants, who met the ROP screening criteria in Department of Neonatology Maternal and Child Health Hospital of Changzhou and with integrated data from July 2011 to July 2014, were analysed in this study. ROP screening was done by ophthalmologist with binocular indirect ophthalmoscope at 4 weeks after birth or chronological age of 32 weeks. According to the screening results they were decided to be treated or not. Data were collected and compared for the severity of ROP in children with different gestational ages and birth weights. Results The detection rate of mild ROP was 5.26%and severe ROP was 0.85%. Birth gestational age<28 weeks and birth weight 500-1 000 g of the children, the risk of severe ROP was significantly increased. The differences were statistically significant (P<0.05). Conclusion Gestational age and birth weight are risk factors for severe ROP. Early detection and treatment can prevent the blindness of ROP.

Evaluating the suitability of using rat models for preclinical efficacy and side effects with inhaled corticosteroids nanosuspension formulations.

Inhaled corticosteroids (ICS) are often prescribed as first-line therapy for patients with asthma Despite their efficacy and improved safety profile compared with oral corticosteroids, the potential for systemic side effects continues to cause concern. In order to reduce the potential for systemic side effects, the pharmaceutical industry has begun efforts to generate new drugs with pulmonary-targeted topical efficacy. One of the major challenges of this approach is to differentiate both efficacy and side effects (pulmonary vs. systemic) in a preclinical animal model. In this study, fluticasone and ciclesonide were used as tool compounds to explore the possibility of demonstrating both efficacy and side effects in a rat model using pulmonary delivery via intratracheal (IT) instillation with nanosuspension formulations. The inhibition of neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and cytokine (TNFα) production were utilized to assess pulmonary efficacy, while adrenal and thymus involution as well as plasma corticosterone suppression was measured to assess systemic side effects. Based on neutrophil infiltration and cytokine production data, the ED50s for ciclesonide and fluticasone were calculated to be 0.1 and 0.03 mg, respectively. At the ED50, the average adrenal involution was 7.6 ± 5.3% for ciclesonide versus 16.6 ± 5.1% for fluticasone, while the average thymus involution was 41.0 ± 4.3% for ciclesonide versus 59.5 ± 5.8% for fluticasone. However, the differentiation became less significant when the dose was pushed to the EDmax (0.3 mg for ciclesonide, 0.1 mg for fluticasone). Overall, the efficacy and side effect profiles of the two compounds exhibited differentiation at low to mid doses (0.03-0.1 mg ciclesonide, 0.01-0.03 mg fluticasone), while this differentiation diminished at the maximum efficacious dose (0.3 mg ciclesonide, 0.1 mg fluticasone), likely due to overdosing in this model. We conclude that the rat LPS model using IT administration of nanosuspensions of ICS is a useful tool to demonstrate pulmonary-targeted efficacy and to differentiate the side effects. However, it is only suitable at sub-maximum efficacious levels.

The clinical curative effect about fog turns to inhale Chuan Le Ning to cure the child′s asthma / 中国实用护理杂志

Objective Inquiring into the clinical curative effect about fog turns to inhale Chuan Le Ning to cure the child′s asthma. Methods Stochastically to divide the 79 examples of acute asthmas into the observation groups(44 examples) with the contrast(35 examples).Two all go the normal regulations for breathe heavily,the ant-infection and handle to the disease.The observation group atomizes to breathe Chuan Le Ning in the foundation. Results FVC,FEV and PEF numbers show the remarkable improvement before the treatment(P