34 research outputs found
Bronchial artery embolization being the therapy of choice for massive hemoptyses in bronchiectases
Introduction. Hemoptyses may be very often due to bronchiectases. Although these bleedings are usually spontaneously resolved recurrent and massive hemoptyses may vitally endanger a patient. Therefore, an urgent diagnosis and treatment of hemoptyses is required. Case report. A 56- year old patient was admitted to the hospital due to massive hemoptyses, presented with a non-homogenous shadowing, paracardially on the left. The chest Computerized Tomography finding delineated atelectasis of the lower left lobe and bronchiectases. Bronchoscopy sampling of the left lung airways provided the fresh blood. The multislice angiography and embolization of the bronchial arteries was carried out, entirely ceasing hemoptyses so the patient was discharged with no symptoms. On the control examination one month later, he was well, with normal radiological finding and inflammation markers. Conclusion. In our patient, the life-threatening bleeding due to inflamed bronchiectases was successfully resolved by bronchial arterial embolization, thus avoiding surgery
Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Development of the chemoresistance in the PDAC is one of the key contributors to the poor survival outcomes and the major reason for urgent development of novel pharmacological approaches in a treatment of PDAC. Systematically tailored combination therapy holds the promise for advancing the treatment of PDAC. However, the number of possible combinations of pharmacological agents is too large to be explored experimentally. In respect to the many epigenetic alterations in PDAC, epigenetic drugs including histone deacetylase inhibitors (HDACi) could be seen as the game changers especially in combined therapy settings. In this work, we explored a possibility of using drug-sensitivity data together with the basal gene expression of pancreatic cell lines to predict combinatorial options available for HDACi. Developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC identified the sphingolipid signaling pathway with associated downstream effectors as a promising novel targets for future development of multi-target therapeutics or combined therapy with HDACi. Through the experimental validation, we have characterized novel synergism between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, and between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod
Association between tobacco smoking and pulmonary tuberculosis
Background/Aim. Numerous studies evaluate the influence of tobacco smoking on the tuberculosis (TB) development, with the results indicating that smoking can be also considered as important risk factor in TB. The aim of this study was to assess the influence of tobacco smoking as the risk factor in the development of TB as well as in its clinical course. Methods. We analyzed data from the medical records of 192 consecutively hospitalized TB patients (124 males and 68 females) in the Institute of Pulmonary Diseases and Tuberculosis, Clinical Center of Serbia, Belgrade in the period from 2005 to 2007. Results. Among the analyzed TB patients there were more smokers (63.5%) than nonsmokers (36.5%). The majority of the smokers (73.8%) belonged to a middle age group (35-54 years) while the majority of nonsmokers (64.3%) were older than 55 years. Sex ratio among the smokers showed the domination of males (80.3%). There were significantly more males in the smoking group and more females in the nonsmoking group (χ2 = 34.402, p < 0.0001). Most smokers (68.9%) smoked more than 20 cigarettes daily. The average index of pack/years among all of the examinated patients was 32.75 ± 18.26. Cavitary pulmonary lesions were more frequently verified in the smokers (64.2%) than in the nonsmokers (35.8%). The sputum acid-fast bacillus smear-positive finding was more frequent in the smokers (78%) than in the nonsmokers (22%). The nonsmoking TB patients had more accompanied immunodeficient diseases (34%) than the smoking ones (19%). Body-mass index was lower in the smokers (21.75) than in the nonsmokers (23.80), although this difference did not reach the statistical significance. Conclusion. There are more smokers than nonsmokers in TB patients. Smokers more frequently have cavitary forms of TB with sputum acid-fast bacillus smear - positive finding than nonsmokers
Occupational exposure to blood and body fluids among health-care workers in Serbia
© 2014 S. Karger AG, Basel. Objectives: The aim of this study was to examine the epidemiology of occupational accidents and self-reported attitude of health-care workers (HCWs) in Serbia. Subjects and Methods: A cross-sectional study was conducted among HCWs in selected departments of five tertiary care hospitals and in one secondary care hospital in February 2012. A previously developed self-administered questionnaire was provided to HCWs who had direct daily contact with patients. χ2 test and Student's t test were used for statistical analysis of the data. Results: Of the 1,441 potential participants, 983 (68.2%) completed the questionnaire: 655 (66.7%) were nurses/medical technicians, 243 (24.7%) were physicians and 85 (8.6%) were other personnel. Of the 983 participants, 291 (29.6%) HCWs had had at least one accident during the previous year and 106 (40.2%) of them reported it to the responsible person. The highest prevalence (68.6%) of accidents was among nurses/technicians (p = 0.001). Accidents occurred more often in large clinical centers (81.1%; p < 0.001) and in the clinical ward, intensive care unit and operating theater (p = 0.003) than in other departments. Seventy-six (13.1%) nurses/medical technicians had an accident during needle recapping (p < 0.001). Of all the HCWs, 550 (55.9%) were fully vaccinated, including significantly more doctors (154, 63.4%) than participants from other job categories (p < 0.001). Conclusion: There was a relatively high rate of accidents among HCWs in our hospitals, most commonly amongst nurses and staff working in clinical wards, intensive care units and operating theaters. The most common types of accidents were needlestick injuries and accidents due to improper handling of contaminated sharp devices or occuring while cleaning instruments or by coming into contact with blood through damaged skin or through the conjunctiva/mucous membranes
A FIRST RECORD OF THE ALIEN MANTIS SPECIES HIERODULA TENUIDENTATA (MANTODEA: MANTIDAE) IN SERBIA
An alien mantis species, Hierodula tenuidentata, has expanded its areal in Europe in the last few years. It was registered in several European countries, including some on the Balkan Peninsula. Herein are presented for the first time records of H. tenuidentata on the territory of Serbia, several from the capital city of Belgrade, and one from Novi Kneževac, a town in the northern part of country. The species was recognized for the first time in photos posted in a Facebook group of insect lovers and enthusiasts in 2019, but positive identification only took place in 2020 after group members collected specimens. Social networks can be a very important tool for the monitoring of invasive species in general, and invasive mantids in particular, especially due to their size and attractiveness
Pouzdanost složenih vodovodnih sistema na primeru RVS Dubovac-Zrenjanin-Kikinda
Water supply networks have a specific feature that makes them more complicated then many other water management systems. Namely, to make sure that the system performs well, apart from the mechanical characteristics of the system, the hydraulic reliability of its components must also be verified. In this particular case the reliability of the regional water supply system Dubovac-Zrenjanin-Kikinda has been assessed, the system being based on the concept of centralized water supply, in which water is conducted from the different regional sources to the municipal centers, and then distributed to the users.Vodovodni (distributivni) sistemi imaju jednu specifičnost koja ih, sa gledišta pouzdanosti, čini složenijim od drugih sistema. Da bi sistem uspešno obavljao svoju funkciju pored pouzdanosti mehaničkih karakteristika sistema uzima se u obzir i pouzdanost hidrauličkih parametara sistema. U ovom radu se na primeru regionalnog vodovodnog sistema Dubovac-Zrenjanin-Kikinda koji se bazira na konceptu centralizovanog vodosnabdevanja dovođenjem vode sa regionalnog izvorišta, preko PPV i dalje regionalnim cevovodima distribuira do opštinskih centara razmatra problem određivanja pouzdanosti vodovodnog sistema
Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation
Abstract Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations
Synthesis and characterization of a new diiminedioxime ligand and its copper (ii) complex as potential 64Cu(ii)-radiopharmaceuticals
As a part of effort to an develop 64Cu-based radiopharmaceuticals for PET
(positron emission tomography) imaging of multidrug resistance in cancer, a new
diiminedioxime ligand was prepared. Its Cu(II) complex was synthesized from
Cu(OAc)2 by heating in methanol. The structure of the ligand was established
using elemental analysis, UV-Vis, IR, 1H and 13C NMR technique. The isolated
complex was characterized by means of elemental analysis, IR and UV-Vis, and its
structure was proposed
99mTc-complex of novel diamine-dioxime ligand
Novel diamine-dioxime ligand, 4,7-diaza-3,8-diethyldecane-2,9-dione bis oxime
(LH2), derivative of hexamethyl-propylene amine oxime (HMPAO), was
synthesized in order to develop new brain perfusion imaging agent, based on
99mTc(V) complexes. The 99mTc(V)-d,l-HMPAO complex is well-known
radiopharmaceutical for brain imaging. The structures of the synthesized
compound were characterized by UV-Vis, IR, 1
H NMR and 13C NMR. The
procedure for radiolabeling of diamine-dioxime with 99mTc was developed and
radiolabeling yield of the 99mTc-complex was followed by paper and thin-layer
chromatography. The maximum radiolabeling yield was obtained when the
reactions were carried out at pH~9 within 10 min at room temperature (RT).
Biodistribution studies on rats has shown significant uptake of 99mTc-complex
(2.1% ID), 2 min after injection.Physical chemistry 2012 : 11th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 201
Towards the multitarget HDAC Inhibitors for the treatment of pancreatic carcinoma by joining the drug synergy predictions and the molecular modeling
Pancreatic ductal adenocarcinoma (PDAC) ranks among the most formidable and deadly
types of cancer. The emergence of chemoresistance in PDAC plays a significant role in the
unfavorable survival rates, making it imperative to swiftly develop new pharmaceutical
strategies to address this issue and improve treatment outcomes for PDAC (1). Considering
the numerous epigenetic changes observed in PDAC, the utilization of epigenetic drugs,
such as histone deacetylase (HDAC) inhibitors, holds a great promise as a transformative
approach, particularly when used in combination therapy settings (2).
In this study, we investigated the potential of utilizing drug sensitivity data and the basal
gene expression of pancreatic carcinoma cell lines to develop a bioinformatics screening
protocol for prediction of the combinatorial options available for HDAC inhibitors, including
sirtuin (SIRT) inhibitors. Experimental validation of the protocol performed on the two
pancreatic carcinoma cell lines (MIA PaCa-2 cells and PANC-1) confirmed the identified
synergisms between HDAC inhibitors and sphingosine 1-phosphate (S1P) receptor agonist
– fingolimod, or HDAC inhibitors and Rho-associated protein kinase (ROCK) inhibitor – RKI1447 (3).
Developed bioinformatics screening protocol for predictions of synergistic drug
combinations in PDAC identified several previously unreported interaction partners of
HDAC inhibitors. Predicted interaction partners of HDAC inhibitors including Aurora Kinase
A (AURKA) inhibitor, glutaminase (GLS) inhibitor and WEE1 kinase inhibitor were selected
for the design of novel classes of dual-acting HDAC inhibitors by the means of structure-based molecular modelling. Novel dual inhibitors (SIRT/AURKA, HDAC/GLS and HDAC/WEE1)
were designed relying on the known pharmacophoric features and molecular docking
models developed for each of the targets of interest. The docking scores of the designed
inhibitors revealed a notable affinity towards the specific targets. Additionally, when
combined with predictions of drug synergy, these designed molecules exhibit great
potential as promising structures for subsequent experimental evaluation.10th IAPC Meeting, Book of Abstract