Mucolytic Properties Research Articles

A phase IIa proof-of-concept, placebo-controlled, randomized, double-blind, crossover, single-dose clinical trial of a new class of bronchodilator for acute asthma

BackgroundThis study evaluates a novel bronchodilator, S1226, for its efficacy in reversing allergen-induced bronchoconstriction in subjects with mild, allergic asthma. S1226 is a new class of bronchodilator that is an aerosol/vapor/gas mixture combining pharmacological and biophysical principles for a novel mode of action. It contains a potent bronchodilator gas (carbon dioxide or CO2) and nebulized perflubron (a synthetic surfactant possessing mucolytic properties). It has demonstrated rapid reversal of allergen-induced bronchoconstriction in an ovine study model.MethodsThis was a phase IIa proof-of-concept, placebo-controlled, randomized, double-blind, crossover single-dose clinical trial to evaluate the safety, tolerability, and efficacy of S1226 (8% CO2) administered by nebulization following an allergen-induced early asthmatic response in 12 subjects with mild, allergic asthma. Primary safety endpoints were adverse events, vital signs, pulse oximetry, and spirometry. Efficacy endpoints included bronchodilator response (measured as the forced expiratory volume in 1 s or FEV1) over time, the area under the curve of FEV1 for the early asthmatic response over time, and achievement of responder status, defined as a 12% improvement after the allergen challenge.ResultsNo significant safety issues were observed. All adverse events were non-serious, mild, and transient. There was a statistically significant decrease in peripheral blood oxygenation levels over time in the placebo group following allergen inhalation, whereas blood oxygenation was maintained at normal levels in the S1226-treated subjects (P = 0.028). This effect was greatest 5 min after start of treatment (P < 0.001). The recovery rate was faster but not significantly so (P = 0.272) for S1226 compared to the placebo at earlier time points (5, 10, and 15 min), as assessed by ≥12% reversal of FEV1. The recovery of FEV1 over time was significantly greater (P = 0.04) with S1226 compared to the placebo.ConclusionsS1226 was safe, tolerated well, and provided bronchodilation and improved blood oxygenation in subjects with mild atopic asthma following allergen-induced bronchoconstriction. Additional studies to optimize the therapeutic response are indicated.Trial registrationClinicalTrials.gov, NCT02334553. Registered on 12 November 2014.

Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis.

BackgroundCystic Fibrosis (CF) is a genetic disorder caused by mutation(s) in the CF-transmembrane conductance regulator (Cftr) gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa), a common CF pathogen, exacerbates obstructive CF lung pathology. In the present study, we aimed to develop and test a novel strategy to improve the bioavailability and potentially achieve targeted drug delivery of cysteamine, a potent autophagy-inducing drug with anti-bacterial properties, by developing a dendrimer (PAMAM-DEN)-based cysteamine analogue.ResultsWe first evaluated the effect of dendrimer-based cysteamine analogue (PAMAM-DENCYS) on the intrinsic autophagy response in IB3-1 cells and observed a significant reduction in Ub-RFP and LC3-GFP co-localization (aggresome-bodies) by PAMAM-DENCYS treatment as compared to plain dendrimer (PAMAM-DEN) control. Next, we observed that PAMAM-DENCYS treatment shows a modest rescue of ΔF508-CFTR as the C-form. Moreover, immunofluorescence microscopy of HEK-293 cells transfected with ΔF508-CFTR-GFP showed that PAMAM-DENCYS is able to rescue the misfolded-ΔF508-CFTR from aggresome-bodies by inducing its trafficking to the plasma membrane. We further verified these results by flow cytometry and observed significant (p<0.05; PAMAM-DEN vs. PAMAM-DENCYS) rescue of membrane-ΔF508-CFTR with PAMAM-DENCYS treatment using non-permeabilized IB3-1 cells immunostained for CFTR. Finally, we assessed the autophagy-mediated bacterial clearance potential of PAMAM-DENCYS by treating IB3-1 cells infected with PA01-GFP, and observed a significant (p<0.01; PAMAM-DEN vs. PAMAM-DENCYS) decrease in intracellular bacterial counts by immunofluorescence microscopy and flow cytometry. Also, PAMAM-DENCYS treatment significantly inhibits the growth of PA01-GFP bacteria and demonstrates potent mucolytic properties.ConclusionsWe demonstrate here the efficacy of dendrimer-based autophagy-induction in preventing sequestration of ΔF508-CFTR to aggresome-bodies while promoting its trafficking to the plasma membrane. Moreover, PAMAM-DENCYS decreases Pa infection and growth, while showing mucolytic properties, suggesting its potential in rescuing Pa-induced ΔF508-CF lung disease that warrants further investigation in CF murine model.

Development and in vitro characterization of a papain loaded mucolytic self-emulsifying drug delivery system (SEDDS)

The aim of the study was to create a self-emulsifying drug delivery system (SEDDS) with mucolytic properties based on incorporated papain for improved mucus permeation. In order to increase the lipophilicity of the enzyme and to dissolve it in SEDDS, hydrophobic ion pairing with sodium deoxycholate in a molar ratio of 20:1 (surfactant: enzyme) was performed. The yield of precipitated papain was 86.8±2.7% and the ion pair was loaded into the formulations to 1% (m/m). Suitable formulations were chosen according to their properties to dissolve the ion pair and characterized regarding droplet size and polydispersity index. Prepared emulsions were in a droplet size range between 50 and 120nm. Enzyme activity assay of complex and loaded SEDDS was conducted to ensure proteolytic qualities for following permeation and diffusion studies. SEDDS loaded with the ion pair showed an almost 2-fold increase in mucus permeation compared to the control without complex. Furthermore, 3-fold enhanced mucus diffusion could be confirmed in a second assay and an increase of mucosal residence on porcine intestinal mucosa up to 3- and 5-fold was observed as against the blank formulations. Consequently the incorporation of enzymes exhibiting proteolytic properties in self-emulsifying drug delivery systems may be considered as a promising strategy to enhance mucus permeation and overcome intestinal barriers.

A Polymer Chemistry Point of View on Mucoadhesion and Mucopenetration.

Although oral is the preferred route of administration of pharmaceutical formulations, the long-standing challenge for medically active compounds to efficiently cross the mucus layer barrier limits its wider applicability. Efforts in nanomedicine to overcome this hurdle consider mucoadhesive and mucopenetrating drug carriers by selectively designing (macromolecular) building blocks. This review highlights and critically discusses recent strategies developed in this context including poly(ethylene glycol)-based modifications, cationic and thiolated polymers, as well as particles with high charge density, zeta-potential shifting ability, or mucolytic properties. The latest advances in ex vivo test platforms are also reviewed.

Acute and Chronic Effects of Oral Erdosteine on Ciliary Beat Frequency, Cough Sensitivity and Airway Reactivity.

Erdosteine as a mucolytic agent that decreases mucus viscosity and facilitates mucus expulsion from the airways by cough or ciliary movement. Our objective was to determine whether erdosteine can directly contribute to mucus clearance. We addressed the issue by monitoring acute and chronic effects of erdosteine on ciliary beat frequency (CBF), cough sensitivity, and airway smooth muscle reactivity. The experiments were performed in healthy guinea pigs. Erdosteine (10 mg/kg) was administrated orally in a single dose or daily through 7 days. The cough reflex and specific airway resistance were evaluated in vivo. The CBF in tracheal brushed samples and the contractile response of tracheal smooth muscle stripes to bronchoconstrictive mediators were evaluated in vitro. We found that neither acute nor chronic erdosteine treatment had a significant effect on cough sensitivity and airway reactivity. However, in the vitro condition, erdosteine increased CBF and reduced tracheal smooth muscle contractility; the effects were more pronounced after chronic treatment. We conclude that erdosteine may directly contribute to mucus clearance by CBF stimulation. Although erdosteine has no effect on cough reflex sensitivity, its mild bronchodilator and mucolytic properties may promote effective cough.

Antibacterial effect of N-acetylcysteine on common canine otitis externa isolates.

N-Acetylcysteine (NAC) has the potential to be a useful therapeutic agent for the treatment of otitis externa due to its antimicrobial and mucolytic properties, as well as its ability to disrupt bacterial biofilm. To determine the antibacterial activity of NAC against common bacterial isolates associated with canine otitis externa. Twenty two isolates from canine clinical cases of otitis externa were identified and tested, including five Staphylococcus pseudintermedius, six Pseudomonas aeruginosa, five Corynebacterium spp. and six β-haemolytic Streptococcus spp. isolates. Each isolate was grown on blood agar for 24h and transferred to Mueller Hinton Broth (MHB) to achieve a final concentration of 5×10(5) CFU/mL. NAC was diluted in MHB to a starting concentration of 160 mg/mL and serial two-fold microdilution assays were performed in triplicate with negative controls for all isolates tested. Concentrations of NAC tested ranged from 0.125 to 80mg/mL. A 50μL volume of bacterial suspension was used to inoculate each well. The minimum inhibitory concentration (MIC) of NAC for all isolates tested ranged from 5 to 20mg/mL. N-Acetylcysteine inhibits clinically relevant and drug resistant bacteria in vitro, and has potential for use as a novel agent for treatment of otitis externa.

Effects of administration of oral n-acetylcysteine on oxidative stress in chronic obstructive pulmonary disease patients in rural population

Background: Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease and the fourth leading cause of death globally. Oxidative stress is an important attribute in the pathogenesis of COPD. Targeting oxidative stress would be a logical therapeutic approach for COPD and glutathione precursors like N-acetylcysteine (NAC) have shown therapeutic promise in the treatment of this chronic pathology. This study attempts to determine the dose related effects of NAC on the oxidative stress, its safety and efficacy in COPD patients. Methods: A randomized, double blind, placebo controlled, parallel group, single centred study, and was carried out in rural set-up. Sixty eight diagnosed cases of COPD according to GOLD criteria (global initiative for chronic obstructive lung disease), were recruited in the study, following approval from the ethics committee. The patients were randomized to three treatment arms (placebo, NAC 600 mg once a day (OD) and NAC 600 mg bis a day (BID). The patients were monitored for incidence and severity of adverse effects as a measure of safety. Efficacy of NAC was determined based on symptom improvement, pulmonary function, oxygen saturation and serum malondialdehyde (MDA) concentration. Results: Results indicate a significant improvement in the efficacy parameters in the group that received higher dose of NAC. NAC was well tolerated by all the study subjects. Addition of NAC to the standard treatment of COPD exhibits beneficial effects in disease exacerbations, symptom improvement and a decline in oxidative stress parameters, reinforcing the antioxidant, anti-inflammatory and mucolytic properties of NAC. Conclusions: This approach opens possibilities for a novel therapeutic approach in COPD.

A Breathe in Cystic Fibrosis Therapy: A New Therapeutic Endeavor for Cysteamine

Cystic fibrosis (CF) is a lethal monogenic disease with mortality and morbidity mostly associated to lung destruction (O'Sullivan and Freedman, 2009). This, in turn, is strictly dependent on recurrent pulmonary infections, with bacteria growing also in biofilms, leading to an unsatisfactory effect of antibiotics (Ratjen and Doring, 2003). The CF registry of patients reports an improvement of both patient survival and quality of life, due to a global care of several aspects of the disease. Yet, it is an unmet need, hence, the urgency of new antibiotics. Recently, Vertex Ph. has introduced in therapy a new potentiator (a channel gating activator), namely ivacaftor (Kalydeco), whose effects, are beneficial, to date, for patients exhibiting the G551D mutation (Ramsey et al., 2011). Furthermore, the same company has introduced a combination of lumacaftor (a corrector of defective CFTR folding/cellular processing, Orkambi) and ivacaftor (Kalydeco) for patients exhibiting F508del-CFTR, the most common mutation (Wainwright et al., 2015). The effects of this approach have been discussed in several papers (see an extensive comment in (Maiuri et al. (2015)). Interestingly, a recent paper reported the effects of Cysteamine in combination with epigallocatechin gallate, in restoring CFTR function and expression at plasma membrane in nasal brushing from CF patients, via rescue of defective autophagy (De Stefano et al., 2014). Noteworthy, cysteamine has received an Orphan Drug Designation in CF also for its mucolytic properties. Such an effect is extremely attractive, being thick mucus an important issue for CF patients. Charrier et al. described the antimicrobial, antibiofilm and mucoactive properties of cysteamine, either alone or in combination with recommended antibiotics, a novel mucoactive antimicrobial and antibiofilm agent for the treatment of CF (Charrier et al., 2014). The authors subsequently reported in the study recently published and herein discussed, that patients were invited to provide their sputum, the most being infected with P. aeruginosa (Devereux et al., 2015). The results of the study prove that daily incubation of sputum with cysteamine significantly decreased the sputum bacterial load and decreased mucus viscosity. The major limitation regarding this study is that no patient has been directly administered. Although cysteamine exhibits also a mucolytic activity that might help in reaching the infected pulmonary site, such an issue must be addressed. Moreover, no characterization of the bacterial type has been provided, meaning that it is also difficult to establish a proper mechanism of action. Finally, the patient mutation type should be taken into account. The study, however, has a great appeal. In fact, cysteamine is an already FDA approved drug for another rare disease, cystinosis, and, thus, in therapy in children. Moreover, side effects have been extensively documented and cysteamine is a safe drug for cystinosis patients although it is well known that pharmacokinetic profile and, thus, tolerability, might be different in CF patients. Moreover, cysteamine is endogenously present, although at very low levels, as a consequence of coenzyme A metabolism (Besouw et al., 2013). The herein cited study, per se, offers the opportunity to address a new mechanism of action for cysteamine and to have a novel drug exhibiting multiple mechanisms of action, being cysteamine an antibiotic, mucolytic and capable of functionally rescuing misfolded CFTR at plasma membrane. These results have been developed from independent research groups and allow to prospectively be positive on the opportunity that cysteamine will be also authorized for CF therapy. In conclusion, there is a strong hope that future studies, carried on with CF patients, will clarify the antibiotic effects of cysteamine, possibly identifying also a dose regimen and, if the case, the bacterial strains that can be treated. Cysteamine, therefore, represents an old drug with several new targets for CF therapy.

Rational Drug Development for Mucous Dehydration and Mucous Metaplasia.

Airway diseases that are clinically characterized by mucous hypersecretion are associated with dehydrated secretions and impaired mucociliary clearance. The failure to clear pro-inflammatory proteases can further exacerbate the mucous dehydration, giving rise to a positive feedback loop that produces a mucous metaplasia and lung remodeling. Increased understanding of the complex mechanisms that regulate airway hydration in health and disease is a prerequisite for rational design of novel therapies. Clinical trials of aerosolized osmolytes and of modulators of epithelial ion channels have provided support for the hypothesis that correcting mucus hydration improves clinical benefit, with the caveat that many of these agents have direct mucolytic properties that are likely to be synergistic with enhanced hydration.

Mucus permeating thiomer nanoparticles

The aim of this study was to develop and evaluate a novel mucoadhesive drug delivery system based on thiolated poly(acrylic acid) nanoparticles exhibiting mucolytic properties to enhance particle diffusion into deeper mucus regions before adhesion. Mediated by a carbodiimide, cysteine and the mucolytic enzyme papain were covalently attached to poly(acrylic acid) via amide bond formation. The conjugates were co-precipitated with calcium chloride in order to obtain papain modified (PAA-pap) and thiolated nanoparticles (PAA-cys) as well as particles containing both conjugates (PAA-cys-pap). The nanoparticulate systems were characterized regarding particle size distribution and zeta potential. Particle transport was investigated by diffusion studies across intestinal mucus using two different techniques. Furthermore, mucoadhesive properties of all particles were evaluated via rheological measurements. Results demonstrated that all nanoparticles were in a size range of 158–214nm and showed negative zeta potentials. Due to the presence of papain, the PAA-cys-pap particles were capable of cleaving mucoglycoprotein substructures and consequently exhibited a 2.0-fold higher penetration into the mucus layer in comparison with PAA-cys particles. Within the rheological studies, an 1.9-fold increase in mucoadhesion could be achieved for the nanoparticulate system based on thiolated PAA compared to papain modified particles (PAA-pap). Therefore, the newly developed particulate system (PAA-cys-pap) is characterized by mucoadhesive as well as mucolytic properties. The combination of both effects – mucus-permeating and mucoadhesive properties – might be a promising strategy for the development of oral drug delivery systems to overcome the mucus barrier and providing a prolonged residence time close to the absorption membrane.

Hepatoprotective Effect of Aqueous Extract of Lippia multiflora Leaves against Ethanol-induced Toxicity in Wistar Rats

Aim: Usually called Tea of Gambia, Lippia multiflora is traditionally used for its sedative, relaxing, febrifuge, anti-flu-like, antispasmodic, hypotensive, anti-inflammatory, anti-catarrhal, mucolytic, antiinfective and hepatoprotective properties. The present study was carried out to evaluate the hepatoprotective effect of aqueous extract of Lippia multiflora leaves against ethanol induced toxicity in rat livers. Study Design: Thirty Wistar albino rats (100-162 g) were divided into six groups of five animals. Original Research Article Bouagnon et al.; EJMP, 7(3): 146-155, 2015; Article no.EJMP.2015.077 147 Group 1 served as control and received only distilled water. Group 2 received only 15%ethanol (3 mL/100 g body weight/day). Group 3 served as standard group and received silymarin (70 mg/kg b.w.). Groups 4, 5 and 6 served as extract treatment groups and received respectively 100, 300 and 900 mg/kg of L. multiflora aqueous extract. 15% ethanol (3 mL/100 g b.w./day) was administered 1h after treatment in groups 3, 4, 5 and 6. Place and Duration of Study: The study was carried out in Laboratory of Biochemical Pharmacodynamy, Felix Houphouet-Boigny University of Cocody-Abidjan (Cote d’Ivoire) between September and November 2014. Methodology: All treatment protocols followed 28 days. Animals received daily doses and were observed for psychomotor changes and other signs of toxicity including death throughout the period of study. At days 7, 14, 21 and 28 of experimental period, blood samples were collected from retroorbital venous plexus in non-heparinized tubes and the serum levels of liver marker enzymes, biochemical metabolites and hematological parameters (numbers of red blood cells, white blood cells, platelet count and mean cell volume)were monitored. Results: L. multiflora extract (300 and 900 mg/kg b.w.) provides significant protection (P<0.05) against ethanol induced toxicity in rat livers showed by reduction of enzymatic parameters activities (ALT, AST and GGT). Histopathological study shows a normal hepatic architecture in L. multiflora extract (300 and 900 mg/kg b.w.) group compared to 15% ethanol group. Additionally, hematological analyses revealan increase of red blood cells and platelet count. A decrease of white blood cells and mean cell volume values in groups treated with 300 and 900 mg/kg of L. multiflora compared to 15% ethanol group is also observed. Conclusion: Our results prove that L. multiflora extract has protective effects against ethanolinduced toxicity.

Anti-tussive, muco-suppressant and expectorant properties, and the safety profile of a hydro-ethanolic extract of &amp;lt;i&amp;gt;Scoparia dulcis&amp;lt;/i&amp;gt;

Background: Scoparia dulcis is used in Ghanaian folkloric medicine for the management of asthma and its related complications. This study was therefore aimed at evaluating the anti-tussive, muco-suppressant and expectorant properties of hydroethanolic extract of S. dulcis (SDE), and to ascertain its safety for use in asthma and obstructive pulmonary disease management. Methods: The number of coughs induced in guinea pigs using citric acid and the concentration of phenol red secreted in tracheae of mice were measured. Preliminary phytochemical analysis was conducted on the extract using standard procedures. Safety for use of the extract was assessed by conducting an acute and delayed toxicity test. Results: The extract showed a dose-independent inhibition (p ≤ 0.001) of cough elicited by 7.5% citric acid, and a dose-dependent increase (p ≤ 0.05) in the amount of phenol red output in mice tracheae similar to that of ammonium chloride. For the muco-suppressant activity, SDE dose-dependently reduced (p ≤ 0.001) the concentration of ammonium chloride-induced phenol red secretions from mice tracheae. Phytochemical screening showed the presence of tannins, alkaloids, glycosides, saponins, steroids, and phenolic compounds. No acute and/or delayed toxic symptoms were observed after an oral administration of up to 5 g/kg of S. dulcis extract. Conclusion: The results showed that S. dulcis extract has anti-tussive, muco-suppressant and, expectorant and/or mucolytic properties; making it a possible remedy for asthma, and obstructive pulmonary disease.

N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine

Context. Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. Objective. Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. Materials and methods. Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 μg.kg− 1, 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml− 1 Mucomyst™ at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. Results. Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO2) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO2) significantly increased, and arterial blood pH and bicarbonate (HCO3−) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO3− levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. Discussion. NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving clinically relevant physiological indices affected by sulfur mustard exposure. Conclusion. Beneficial effects of nebulized NAC were apparent following inhaled sulfur mustard exposure. Further therapeutic benefit may result from a combination therapy approach.

Efficacy of cineole in patients suffering from acute bronchitis: a placebo-controlled double-blind trial

ObjectiveCineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole.MethodsAs part of a double-blind, placebo-controlled, multi-center-study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 x 200 mg of Cineole, or a respective placebo, per day. The primary outcome measure was a Bronchitis Sum Score, which summarises the relevant symptoms of acute bronchitis.ResultsAfter 4 days of treatment it was notable, that the patient group treated with Cineole, showed significantly more improvements of the bronchitis-sum-score than those of the placebo group (p = 0.0383). The statistical significant difference of the individual outcome measures was especially underlined by the frequency of cough fits by p = 0.0001 after 4 days.ConclusionsThe effects of Cineole in the treatment of acute bronchitis were clearly measurable and could be proven after a treatment period of merely 4 days. This study corroborates the fact that Cineole actively and significantly reduces cough frequency after four days. Therefore it has been shown to have a great socioeconomic impact.Trial registrationISRCTN: ISRCTN37784439

The Rational Use of Mucolytic Drugs in Children: Worsening of the Cough as Adverse Drug Reaction after Carbocysteine in Children

Carbocysteine and acetylcysteine are drugs with mucolytic and expectorant properties widely used in respiratory disease in adults but also in children. Acetylcysteine is also used as donor of SH groups in the drug overdose such as in the acetaminophen poisoning. Chronic cough is a vexing and common problem for children, their care givers, and health care providers. Effective treatment may be difficult, especially if the underlying cause of the cough cannot be determined. On the other hand, asthma, recurrent wheezing, bronchiolitis and both upper and lower respiratory tract disease are very common seen in paediatric emergency department. We have tried to found any relationship between use of drugs which are containing carbocysteine and some symptoms such as persistent cough, recurrent wheezing or bronchospasm. We are considering these symptoms as adverse drug reactions of carbocysteine. Our work was focused on 191 children divided in two groups: group A (who received carbocysteine) and group B (without carbocysteine). Our work shows that in all cases of worsening of cough, this effect was credited on the use of carbocysteine. On the other hand, worsening of cough (as frequency and duration) often causes the appearance of reflex vomiting. In case of the late condition the number of hospital admission is increased. Overall we believe that the use of carbocysteine in children exceeds the therapeutic benefit.

Clinical efficacy of Jalaukawacharana (leech application) in Thrombosed piles

‘Arsha’ (hemorrhoids) is an ailment that affects all economical groups of population. Though the disease is within the limits of management, it has its own complications like severe hemorrhage, inflammation, and thrombosis, by which a patient gets severe pain and is unable to continue his routine work. Prior to surgical treatment of hemorrhoids, associated conditions like inflammation, strangulation, thrombosis, etc. need to be managed. Thrombosed piles possibly occur due to high venous pressure associated with severe anal pain. Leech (Hirudina medicanalis) application is found to be effective in reducing pain. In thrombosed piles, leech application has shown thrombolytic action, which contributes in re-establishment of circulation. It is observed in the study that, pus and mucous discharge have been reduced after leech application; which may be due to antimicrobial and mucolytic properties of leech. This method of treatment is found to be effective and increase the quality of life in patients suffering with thrombosed piles.

Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

Mucolysis by Ascorbic Acid and Hydrogen Peroxide on Compact Mucin Secreted in Pseudomyxoma Peritonei

This study examines the potential efficacy of hydrogen peroxide and ascorbic acid in the dissolution of mucinous ascites from pseudomyxoma peritonei. The mucolytic action of both ascorbic acid (0%-0.2%) and hydrogen peroxide (0%-3%) are investigated as single agent on mucin samples derived from patient. This was followed by examining the joint action of ascorbic acid (0.2%) and hydrogen peroxide (0%-3.0%) on mucin. To lower the concentration of hydrogen peroxide in the mixture, the action of equal concentration of ascorbic acid/hydrogen peroxide ranging from 0%-0.3% are then examined. Finally, the pH (4.5-7.0) effect on mucolytic properties of equal concentration (0.2%) of ascorbic acid/hydrogen peroxide was studied. At the concentrations examined (0%-0.2%), ascorbic acid showed highest mucolytic activity at 0.2%. Similarly, hydrogen peroxide as a single agent (0%-3.0%) showed highest mucolytic activity at 3.0%. The mucolytic action of hydrogen peroxide (0%-3.0%) containing 0.2% ascorbic acid demonstrated synergistic effects. At equal concentration of the two agents, ranging from 0%-0.5%, maximal mucolytic action was observed at 0.2%. The mucolytic property of the final mixture (0.2% ascorbic acid/0.2% hydrogen peroxide) was pH-dependent and showed maximal degradation at pH 4.5 and declined as it reached towards neutral pH. The current study introduces the potential applicability of a formulation that holds promise as a mucolytic agent in patients with mucinous ascites from pseudomyxoma peritonei.

The Potential Role of N-Acetylcysteine for the Treatment of Helicobacter pylori

The Potential Role of N-Acetylcysteine for the Treatment of Helicobacter pylori

Constituents of Verbascum reeseanum

The genus Verbascum (Scrophulariaceae) is represented by 228 species, of which 185 are endemic in the flora of Turkey and East Aegean Islands [1]. Verbascum species contain biologically active compounds, such as flavonoids, phenylethanoid and neolignan glycosides, saponins, and iridoid and monoterpene glycosides [2]. The leaves and flowers of Verbascum are reported to have expectorant, mucolytic and demulcent properties, and are used to treat respiratory disorders such as bronchitis, dry coughs, tuberculosis and asthma in traditional Turkish medicine [3].