Carbocysteine in the Management of Stable COPD: Are Its Antioxidant and Anti-Inflammatory Properties Clinically Relevant?

BACKGROUND: The recent epidemiological and experimental evidence suggest possible antioxidant effect of carbocysteine in patients with chronic obstructive pulmonary disease (COPD).AIM: To assess efficacy and tolerability of carbocysteine in the management of stable COPD.METHODS: We performed an observational, non-randomized, open study (a real life study) including 87 patients with stable COPD (group B and D by combined COPD assessment) divided in two groups, examined group (EG) and control group (CG). All participants were treated with the regular treatment of the stable disease, but in the participants of the EG carbocysteine 1,500 mg daily was added to their regular treatment during the period of two months. The study protocol included completion of the COPD Assessment Test (CAT) and spirometric measurements at initial visit and at the end of the mentioned period.RESULTS: We found significantly lower mean value of the overall CAT score in the EG at the end of the study as compared to its mean value registered at initial visit (26.9 vs. 24.3; P = 0.007). In regard to certain CAT items, we found significantly lower values of the mean scores related to cough phlegm and sleep disturbances as compared to their mean scores at initial visit. In addition, the mean values of the overall CAT scores at initial visit and at the end of the study in controls were similar. In EG we found significantly higher mean value of the MEF 25-75 at the end of the study as compared to its mean value registered at initial visit (59.3% vs. 67.2%; P = 0.003). There was no significant difference in the mean values of other spirometric parameters at the end of the study as compared to their mean values at initial visit. In controls we registered similar values of all measured spirometric parameters at the end of the study as compared to their values registered at initial visit. Mild gastrointestinal manifestations were registered in 13.3% of the participants of the EG during the examined period.CONCLUSION: Our findings indicate positive effects of carbocysteine regarding the symptoms and lung function, as well as its good tolerability in the patients with stable COPD.

Factors Associated with Successful Mobilization and Collection of Peripheral Blood Hematopoietic Stem Cells in Autologous and Allogeneic Donors

BACKGROUND: Peripheral blood hematopoietic stem cells (PBSC) have largely replaced bone marrow derived stem cells in autologous transplantations, and have become the preferred source of stem cells in the majority of allogeneic transplantations. Sufficient number of mobilized and collected hematopoietic stem cells (HSC) is needed for successful hematopoietic stem cell transplantation.MATERIAL AND METHOD: This study was performed in the Institute for Transfusion Medicine of RM and the University Clinic of Hematology from 2008 till 2016. There were 30 allogeneic and 90 autologous donors that underwent mobilization and collection of PBSC. The association between possible predictive factors such as demographic characteristics, laboratory parameters and collection parameters in both groups, and mobilization strategy and clinical characteristics in autologous donors and number of collected PBSC was analyzed.RESULTS: There were 226 apheresis, 182 in autologous donors (mean 2, range 1-3) and 44 apheresis in 30 allogeneic donors (mean 1.5, range 1-2). The mean number of collected MNC in autologous donors was 3.09 x 108/kg and 2.85 x 106/kg CD34+ cells, and 3.23 x 108/kg MNC and 3.20 x 106/kg CD34+ cells in allogeneic donors. Significantly larger number of MNC and CD34+ cells was collected with the WBC set. There was a statistically significant correlation between the total number of collected MNC in autologous donors and platelet count before mobilization, the number of cycles in one apheresis procedure, quantity of collected graft and the number of collected MNC and CD34+ cells on the first day of harvestration. There was a statistically significant correlation between the total number of collected MNC in allogeneic donors and platelet count before mobilization, the number of cycles in one apheresis procedure, quantity of collected graft and number of MNC on first day of harvestration. There was a strong correlation between the number of collected MNC and CD34+ cells on the first harvest and the total number of collected MNC and CD34+ cells in poor mobilizers, and inverse correlation with the number of apheresis procedures. Donors who donated MNC ≤ 0.7 x 108/kg and/or ≤ 0.7 x 106/kg CD34+ cells on the first harvest (84.6%) were strong predictors of poor mobilizers.CONCLUSION: Determining the proper level of baseline and preaheresis laboratory parameters for initiating mobilization and apheresis procedure which is safe for donors and greatly efficient in collection of PBSC is needed for optimization of these procedures, as well as for early intervention in poor mobilizers.

Biomarkers of Inflammation in Peripheral Blood during Treatment with Inhaled Corticosteroids in Patients with Asthma

BACKGROUND: The main attribute of asthma is inflammation, which leads to airway remodelling, bronchial hyper-reactivity and reversible or partly reversible airway obstruction. According to GINA, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular, mast cells, eosinophils (Eo), and T lymphocytes. Many cells and mediators take part in creating the asthmatic inflammatory reaction, but eosinophils play a central role.AIM: The aim of this study was to show the values of biological inflammatory markers (IL-5, Eo, and ECP) during treatment with ICS by non-invasive methods.MATERIAL AND METHODS: This study includes 30 patients of the Pulmonology and Allergology Clinic, Skopje, with confirmed asthma, treated with ICS. In all of the patients, we followed Eo count, ECP and IL-5 in peripheral blood at the beginning of the study, after 2 and six months treatment. Following the parameters during treatment with ICS we registered changes in all of the tested parameters.RESULTS: Our results show high level of the tested biomarkers at the beginning of the study, IL-5 in all patients (100%), Eosinophils in 80%, and ECP in 90% of the asthmatics. Following the parameters during treatment with ICS we registered changes in all of the tested parameters.CONCLUSIONS: Our conclusion is that the ICS objectively suppress the inflammatory reaction in asthma and the biologic markers (IL-5, Eo and ECP), which we have followed, can measure the accomplished effect. They could be used in everyday practice, not only as diagnostic parameters but also as valid therapeutic guides in the treatment of asthma.

CD56dim/CD56bright NK cell subpopulations and CD16/CD57 expression correlated with tumor development stages

BACKGROUND: NK cells are characterized by cytotoxic activity against tumor cells and CD3-CD16+CD56+ phenotype. Two distinct subpopulations of NK cells were characterized in the peripheral blood: NK-CD56dim representing over 95% of NK cells and involved in antitumor cytotoxicity, and NK-CD56bright representing approximately 10% of NK cells and involved in secretion of cytokines.AIM: The aim of the study was to compare the presence of NK-CD56dim/NK-CD56bright subpopulations and their CD16/CD57 expression in peripheral blood NK cells during the particular development stages of malignancy: primary tumor (PT), lymph node invasion (LNI) and distant sites metastases (Mt). MATERIAL AND METHODS: We have analyzed by flow-cytometry peripheral blood samples from total 36 cancer patients: 24 patients with PT, 6 patients with LNI and 6 patients with Mt.RESULTS: The presence of the overall NK cells showed no significant variation between patients in different stages of tumor development. The phenotype analysis showed that CD16+ and/or CD57+ cells were lower in LNI patients compared to PT or Mt patients. Double-positive CD16+CD57+ cells were found decreased in patients with Mt, compared to patients with PT. During the stages of tumor development, NK-CD56bright subpopulation increased progressively (7% in PT patients, 13% in LNI patients, 65% in Mt patients), whereas NK-CD56dim subpopulation gradually decreased (92%, 86%, and 35% respectively). CD16/CD57 expression decreased in NK-CD56dim and increased in NK-CD56bright cells over the three studied stages.CONCLUSION: Our results show changes in NK cells characteristics during tumor development: reversal of NK-CD56dim/NK-CD56brightdistribution and modification of CD16/CD57 expression. Both types of changes can concur in reducing the efficiency of NK cell activity in patients with progressive tumors.

ROS-mediated Cytotoxicity and Macrophage Activation Induced by TiO2 Nanoparticles with Different in vitro Non-Cellular Photocatalytic Activities

AIM: The aim of the study described in the present paper was to assess several in vitro effects of TiO2 nanoparticles with different colloidal and photocatalytic properties on RAW 264.7 macrophages.METHODS: The cells were exposed to Degussa P25 titania and two other types of nanoparticles synthesized by a hydrothermal procedure in our laboratory: undoped and Fe3+-doped TiO2. Compared to Degussa P25, the hydrothermal nanomaterials were significantly less active in inducing cytotoxicity, production of intracellular reactive oxygen species (ROS) and release of pro-inflammatory cytokine interleukin-6 (IL-6). The induced effects were analysed with respect to nanoparticle size, surface charge, hydrophilicity, semiconductor bandgap energy and photocatalytic generation of ROS under non-cellular conditions.RESULTS: The overall results indicated that TiO2 nanoparticles with higher surface charge, hydrophilic surfaces and enhanced photocatalytic properties may preferentially induce macrophage cell damage and inflammation compared to other TiO2 nanomaterials.CONCLUSION: The present findings are relevant for studies regarding the evaluation of risks raised by self-cleaning technologies involving nanosized hydrophilic TiO2 photocatalysts as well as development of synthesis methods optimized for producing biocompatible TiO2 nanomaterials.

Occupational Exposure and Co-Occurrence of Work-Related Skin and Respiratory Disorder in Cleaner: A Case Report

BACKGROUND: Despite the connection between skin and respiratory system in occupational disease is growing area of research interest, there is still a limited evidence for the effects of both airborne and skin exposures together with skin and respiratory outcomes.CASE PRESENTATION: This report describes a 32-years old female with no previous history of atopy, asthma or skin disorders working as an office cleaner for three years. About two years after entering the actual workplace she developed episodic wheezing, shortening of breath and chest tightness. At the same time, she noticed eczematous lesions on the skin of both hands. She reported work-relatedness of both respiratory and skin symptoms, i.e. the symptoms improved during weekends and holidays and worsened when she returned to work. The patient was referred to Institute for Occupational Health of R. Macedonia for assessment of possible occupational asthma (OA) and occupational contact dermatitis (OCD). Diagnosis of asthma was confirmed by standard diagnostic procedure, while the diagnosis of sensitizer-induced OA was established by positive result of serial peak expiratory flow rate (PEFR) measurements at and away from work. Diagnosis of allergic OCD was confirmed by positive patch test to formaldehyde. The management of both diseases included complete removal from the harmful workplace exposure, as well as pharmacological treatment according to the actual recommendations.CONCLUSIONS: This case report represents a description of a co-occurrence of work-related skin and respiratory symptoms in a female working as an office cleaner. Formaldehyde is found to be a causative factor of allergic OCD, and it also may be a causative factor of sensitive-induced OA in the same patient, but other occupational sensitizers cannot be excluded.

Late Diagnosis of Takayasu Arteritis with Cardiac Involvement: Case Report

Takayasu arteritis (TA) is an idiopathic chronic granulomatous vasculitis that affects aorta, its main branches and occasionally pulmonary arteries. It is more common in Asian persons, affecting predominantly young women. Clinical presentation is nonspecific at the beginning of the disease, while in the ischemic disease’s stage it depends on the territories affected. We present the case of a 26-year-old woman who was diagnosed as having TA. Multiple vascular abnormalities of aorta and its branches and severely reduced left ventricular function were present at the time of diagnosis. Immunosuppressive treatment consisting of prednisone and azathyoprine along with conventional heart failure therapy significantly improved her cardiac function.