Melatonin inhibits apoptosis and oxidative tissue damage in cisplatin-induced pulmonary toxicity in rats.

Introduction: Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis. Material and methods: The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases. Results: Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only. Conclusions: These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.

Lycopene and Caffeic Acid Phenethyl Ester Affect Caspase-3 Activity, but Do Not Alter the NO Pathway in Lung Tissue Damage Induced by Cisplatin.

INTRODUCTION: Antioxidants such as lycopene (LCP) and caffeic acid phenethyl ester (CAPE) represent ideal molecules for the treatment of different reactive oxygen species (ROS) associated disorders. Cisplatin is a chemotherapeutic agent, causing an increase in ROS and DNA damage, with numerous side effects, which include lung toxicity. In the presents study, we evaluated and mutually compared the potential of LCP and CAPE in preventing cisplatin-induced rat lung damage. METHODS: The study was done using pathohistological analysis and a panel of biochemical parameters that reflect lung oxidative tissue damage, inflammation, and apoptosis. RESULTS: The obtained results suggest that cisplatin (10 mg/kg) causes significant disturbances in the lung tissue morphology, followed by an increase in lipid peroxidization and protein modification. Also, a pronounced inflammatory response and cell apoptosis cascade activation was noted. Both LCP and CAPE were able to mitigate the changes, to a different extent, in oxidative damage and apoptosis progression induced by cisplatin. However, they both had limited effect on inflammation since they only prevented an increase in myeloperoxidase activity but had not been able to prevent the NO generation. CONCLUSION: It is hard to be exact in saying whether LCP or CAPE is better in preventing cis-platin-induced lung damage since they obviously possess different mechanisms of action.

Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis - limitations for the underlying COPD detection.

BACKGROUND: During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. PURPOSE: The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. PATIENTS AND METHODS: Prospective, nest case-control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. RESULTS: From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (P<0.01). Their changes in forced expiratory volume in the first second (%) during the PTB treatment were strongly associated with the air pollution exposure in living (0.474%-20.971% for 95% confidence interval [CI]; P=0.041) and working environments (3.928%-20.379% for 95% CI; P=0.005), initial radiological extent of PTB lesions (0.018%-0.700% for 95% CI; P=0.047), leukocyte count (0.020%-1.328% for 95% CI; P=0.043), and C-reactive protein serum level (0.046%-0.205% for 95% CI; P=0.003) compared to the other patients. The multivariate logistic regression analysis model shows initial radiological extent of pulmonary tuberculosis lesions (OR 1.01-1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02-1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. CONCLUSION: AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel dust exposure. Initial spirometry testing in patients with active PTB is not a sufficient and accurate approach in the detection of underlying COPD, which may lead to their further potential health deterioration.

Pulmonary function parameters as prognostic factors in advanced non-small cell lung cancer.

AIM: To investigate the impact of some parameters of lung function (forced expiratory volumen in 1 second - FEV1, forced vital capacity - FVC and ratio FEV1/FVC%) on survival in patients with advanced non-small cell lung cancer (NSCLC). METHODS: It retrospectively analyzed data of 155 patients with NSCLC receiving second-line treatment in the Clinic for Lung Diseases, Clinical Center Nis, Serbia, from October 2009 to December 2012. Fifteen potential prognostic variables were subjected to univariate and multivariate analysis to investigate prognostic impact to survival. RESULTS: Among the total of 155 patients, 124 (80%) were males. The most frequent was squamous carcinoma, 86 (55,5%). Mean FEV1 was 1.89 ± 0.71 L (61.8%), mean FVC 2.95 ± 0.8 L (77.2%) and mean FEV1/FVC% was 63.6%. In a multivariate analysis using Cox regression hazard model (hazard ratio, HR), independent prognostic factors for overall survival (OS) were: FEV1 less than 50% of predicted HR= 4.513, 95% confidence interval (CI): 1.433-14.216 (p=0.010), performance status 2 (HR= 0.090, CI= 0.035-0.230 (p=0.000) and weight loss more than 5 % (HR= 0.162, CI= 0.068-0.382 (p=0.000). CONCLUSION: FEV1 in patients with advanced NSCLC receiving chemotherapy is an important independent factor that can predict survival. There was close relationship between impaired lung function and lung cancer patients survival.

Challenges in the diagnosis and treatment of recurrent non-resolving pneumonia - the case of foreign body aspiration in adult mimicking lung neoplasm.

Foreign-body tracheobronchial aspiration in adults is fairly rare, and it is caused mostly by the failure of airway protective mechanisms. The symptoms of this clinical entity can mimic many other respiratory diseases, such as recurrent or non-resolving pneumonia, asthma, lung neoplasm etc. Flexible bronchoscopy was indicated in this situation, both for diagnostic and therapeutic purposes. We are reporting on a case of a fiftythree- year old women with recurrent, non-resolving pneumonia, recurrent hemoptysis, dyspnea, fiver, chest pain and radiological presentation of middle lobe neoplasm caused by aspirated chicken neck bone.

Nutrition disorder and systemic inflammation in patients with chronic obstructive pulmonary disease.

AIM: To detect nutrition disorders (underweight and obesity) in patients with chronic obstructive disease (COPD) and presence of systemic inflammation by determination of inflammatory mediators serum values C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α) and leptin. METHODS: The examination involved 85 patients with COPD. Nutrition categories were defined by body mass index (BMI). Fat free mass (FFM) was evaluated by mid upper-arm circumference (MUAC) and fat mass (FM) by tricipital skin-fold thickness (TFS). Values of TNF-α and leptin were measured by standardized ELISA kits and, CRP by latex turbidimetry. RESULTS: There were 14 (16.5%) underweight patients, 28 (32.9%) normal, 28 (32.9%) pre-obese and 15 (17.6%) obese. Values of MUAC and TSF were significantly different among the nutrition categories (p=0.000). The lowest MUAC and TSF values were in the underweight, and the highest in the obese. There was no significant difference of CRP and TNF-α among nutrition categories. Leptin of the underweight and normal nutrition was significantly different from leptin of the pre-obese and obese (p=0.000). The highest CRP and the lowest TNF-α and leptin were in the underweight patients. The obese had the lowest CRP (although increased as compared to normal values) and the highest leptin, while the pre-obese had the highest TNF-α. CONCLUSION: Two basic nutrition disorders (underweight and obesity) were manifested in COPD patients. The inflammatory profile differs between underweight COPD patients and obese. Probably that happens due to systemic inflammation, and in part due to dysfunction of adipose tissue.

[Infective complications in patients with lung cancer].

INTRODUCTION: This study was aimed at analyzing the site, kind and type of infection which develop in patients having lung cancer at hospital treatment. MATERIAL AND METHODS: Clinical data of the patients hospitalized for lung cancer were analyzed at the Clinic for Lung Diseases and Tuberculosis in Knez Selo in the period from January 2002 till December 2007. A great number of patients (1296-75.9%) had non-small cell lung cancer. In 1708 patients with lung cancer, 773 febrile episodes were recorded, i.e. 687 states of infections. RESULTS: Most of the infections were recorded in the tracheobronchial tree (60.9%). The infection was confirmed microbiologically in 38% of infectious states. Predominant Gram positive pathogens were Staphylococcus aureus and Streptococcus, but among Gram negative pathogens there were Escherichia coli and Haemophilus influenzae. DISCUSSION: A significantly better therapy response to antibiotics was found in the group of patients where microbiological agents were isolated (p < 0.05). The predominant site of infection in the patients with lung cancer is the tracheobronchial tree without a significant difference between frequency of Gram positive and Gram negative pathogens.

Difficulties in establishing a timely diagnosis of pulmonary artery sarcoma misdiagnosed as chronic thrombo-embolic pulmonary disease: a case report.

INTRODUCTION: Pulmonary artery sarcomas are rare neoplasms that are often confused with chronic thrombo-embolic disease, as both can have similar clinical and imaging presentation. CASE PRESENTATION: In this report, we present a case of a 50-year-old man initially diagnosed with chronic thrombo-embolic pulmonary disease, but who was later found to have pulmonary artery sarcoma with poor survival prognosis. We review the clinical and imaging characteristics of the two diseases and discuss the difficulties in establishing a timely diagnosis. CONCLUSION: Similar clinical features and imaging presentation of pulmonary artery sarcoma and chronic thrombo-embolic pulmonary disease make definitive diagnosis difficult. This case report also illustrates and emphasizes that in any case with no predisposition factors for embolism, no evidence of deep venous thrombosis and pulmonary emboli, and inadequate relief of symptoms with anticoagulation, an alternative diagnosis of pulmonary artery sarcoma should be considered. If pulmonary artery sarcoma is diagnosed late in the course of the disease, there is usually a poor survival outcome.

Diagnostic value of CEA in pleural fluid for differential diagnosis of benign and malign pleural effusion.

UNLABELLED: The diagnostic value of tumor markers in pleural fluid is still the subject of debate. The aim of this work was to evaluate diagnostic value of carcinoembryonic antigen (CEA) in pleural fluid for differentiating malignant from non malign pleural effusion, and their additive value to cytological examination. DESIGN: Prospective, case control study. SETTING: Tertiary University hospital, Clinic for Lung Disease, Knez Selo. PATIENTS: Eighty two patients with pleural effusion, forty one with malignant, and forty one with non malignant pleural effusion. MEASUREMENTS AND RESULTS: Levels of CEA in pleural fluid was measured by IRMA CEA methods, INEP Belgrade. Patients with lung cancer were found to have significantly higher CEA levels than patients with non malign pleural effusion. Using cut off values of 2.4 ng/ml, the sensitivity of marker was 78%, and specificity 95.1% (CI 95%). The addition of CEA to cytology increase diagnostic rate from 68 to 85.3%. CONCLUSION: CEA may represent a helpful adjunct to cytology in order to include malignancy as probable diagnosis, thus guiding the selection of patients for more invasive procedures.

[Gastrointestinal stromal tumors--microscopic and immunihistochemical features].

BACKGROUND/AIM: Gastrointestinal (GI) stromal tumors (GIST) are the most common mesenchymal tumors of GI tract. The most frequent localization is gastric (60-70%) followed by intestinal localization (20-30%). The histogenesis, classification, diagnostic criteria and biological behavior of GIST are still discussable. Gastrointestinal stromal tumors are thought to originate from interstitial pacemaker intestinal cells of Cajal. Histologic appearance of a GIST is complicated and biologic potential unpredictable. The aim of of tha study was to investigate anatomic localization, the size of the tumor, incapsulation, microscopic and immunohistochemical characteristics. METHODS: The study involved 21 GIST taken by a complete resection in the period from 1994-2006. The analysed parameters were the localization, size, microscopic (mitotic index, nectosis, bleeding, invasivity) and immunohistochemical characteristics (CD117 (c-kit), CD34, desmin, vimentin, smooth muscle actin and s-100 protein expression. RESULTS: Gastrointestinal stromal tumors (n=21) size varied from 10-150 mm were most frequently gastric localised with predominance of malignant tumors (85.72%). Most GIST were comprised of a uniform spindle cell population, but some were dominated by epitheloid cells. Eosinophilic cells stained CD117, CD34 and vimentin positively, were usually arranged in fascicles with the presence of skeinoid fibers. Positive correlation of biologic potential and tumor size, haemorrhagia and mitotic index were found, so as negative correlation of biologic potential and incapsulation. CONCLUSION: The above results, a specially localization, tumor size, mitotic index, CD117, CD34 and vimentin positivity, may be helpful for setting of a widespread criteria for diagnostic and differential diagnosis of GIST and their use in practice and therapy.