EMERGENCY TRACHEOTOMY IN TRACHEAL STENOSIS - A CASE REPORT.

Airway management in an emergency department is the first step in critical care of an urgent patient. When orotracheal intubation is not possible due to upper airway obstruction, such an emergency is known as a 'cannot intubate - cannot ventilate' situation. Then, emergency tracheotomy is indicated. We present a case of a 70-year-old patient complaining of progressive dyspnea. The patient was conscious, highly tachydyspneic, and tachycardic. Loud stridor and a scar from previous tracheostomy suggested upper airway obstruction. Patient history confirmed previous partial laryngectomy and temporary tracheostomy due to laryngeal cancer 10 months before. Differential diagnosis of tracheal stenosis was set, and an ENT specialist was requested. Flexible fiberoptic laryngoscopy demonstrated a 1-mm subglottic tracheal stenosis. Emergency surgical tracheotomy below the obstruction in awake state using local anesthesia was performed to secure the airway. Early postoperative care was complicated by incipient right-sided pneumonia, which may have provoked narrowing of the existing subglottic stenosis in the first place. Tracheal stenosis is an important differential diagnosis of airway obstruction in patients with previous malignant diseases of the upper respiratory system. Emergency physicians should promptly recognize these situations based on clinical examination to secure appropriate airway management.

Circulating levels of IL-6 and TGF-ß1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms.

BACKGROUND: The goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-ß1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue. METHODS: Thirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-ß1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA. RESULTS: The significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-ß1 levels and maximum genitourinary toxicity grades and between TGF-ß1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-ß1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-ß1 concentrations measured after the 25th fraction and maximum fatigue scores were observed. CONCLUSIONS: Our results suggest that serum levels of IL-6 and TGF-ß1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

Antimicrobial and Cytotoxic Activities of Selected Hieracium L. s. str. (Asteraceae) Extracts and Isolated Sesquiterpene Lactones.

Antimicrobial and cytotoxic activities were tested for dried MeOH extracts of Hieracium calophyllum (CAL), H. coloriscapum (COL), H. pseudoschenkii (PSE), H. valdepilosum (VAL) and H. glabratum (GLA) herbs (flowering aerial parts), their 2 sesquiterpene lactones (SLs) 8-epiixerisamine A and crepiside E, and dried CH2 Cl2 extract of H. scheppigianum (SCH) herb. In microdilution test, extracts showed activity on all tested microorganisms (8 bacteria, 10 fungi). The best effect was exhibited by SCH and CAL on Salmonella Typhimurium (MIC=1.7-2.5 mg/mL MBC=3.4-5.0 mg/mL), and SCH and VAL on Candida albicans (MIC=2.5 mg/mL MFC=5.0 mg/mL). SLs showed notable effect on all tested fungi Aspergillus ochraceus, Penicillium funiculosum, C. albicans and C. krusei (MIC=0.15-0.4 mg/mL MFC=0.3-0.8 mg/mL). In MTT test, extracts inhibited growth of all tested cancer cells (HeLa, LS174 and A549), with the best effect on HeLa (IC50 =148.1 µg/mL for SCH, and 152.3-303.2 µg/mL for MeOH extracts); both SLs were active against HeLa cells (IC50 =46.2 µg/mL for crepiside E and 103.8 µg/mL for 8-epiixerisamine A). Extracts and SLs showed good safety profile on normal MRC-5 cells.

Are the Persistent Postural-Perceptual Dizziness (PPPD) Patients More Anxious than the Patients with Other Dizziness?

BACKGROUND: The Behavioral Subcommittee of the Bárány Society Committee for Classification of Vestibular Disorders recently established the diagnostic criteria for a persistent postural-perceptive dizziness (PPPD). OBJECTIVES: This study aims to determine how significant the degree of anxiety and depression of PPPD patients is, compared to the patients with other dizziness. SUBJECTS AND METHODS: The study was conducted on 78 patients, 39 (50%) of whom suffer from PPPD, and of a control group consisting of the same number of patients with other types of dizziness. All the patients filled out the DHI and HADS questionnaire and were subjected to a VNG and VEMP examination. RESULTS: The DHI showed significant disability in the majority of patients, slightly more in the control group. The HADS showed an equal degree of anxiety in both groups of patients, but significantly higher pathological anxiety in the PPPD group (49%:31%). CONCLUSIONS: Majority of the patients in both groups experienced mild anxiety, while those with the pathological degree were more represented in the PPPD group. Depression was more expressed in the group of other dizziness. We can consider only the patients with a pathological degree of anxiety as predisposed to the emergence of PPPD.

RARE LARYNGEAL HAMARTOMA: A CASE REPORT.

Hamartoma (from the Greek language, where hamartia means defect or an error and -oma denoting a tumor or neoplasm) is a benign tumor-like mass composed of mature tissue or cells that are present in abnormal proportions or show a disorganized arrangement. Hamartomas are rarely seen in the head and neck area and especially rare in the larynx. Only few cases of laryngeal hamartoma have been reported in the literature so far. They are usually manifested by stridor, dysphonia and symptoms associated with airway obstruction. The diagnosis must be confirmed histologically and the method of choice in treatment is complete excision of the lesion. The authors present a case of laryngeal hamartoma of a 43-year-old woman treated for hoarseness and paralysis of the left vocal cord.

Synthesis, characterization, antimicrobial and cytotoxic activity and DNA-binding properties of d-metal complexes with hydrazones of Girard's T and P reagents.

In this work synthesis, characterization and crystal structures of 1, Zn(II) complex ([ZnL1(NCS)2]), with (E)-1-(2-oxo-2-(2-(quinolin-2-ylmethylene)hydrazinyl)ethyl)pyridin-1-ium chloride (HL1Cl) and 2, Bi(III) complex ([BiHL2Cl4] × 1/2CH3OH), with (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL2Cl), have been reported. Zn(II) complex possesses a distorted trigonal bipyramidal geometry while surroundings around Bi(III) ion are extended pentagonal bipyramidal. Antimicrobial activity, brine shrimp assay and DPPH radical scavenging activity of both complexes, including previously synthesized complexes with HL2Cl ligand (Zn(II) and Ni(II)) and complexes with (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL3Cl) (Zn(II), Cu(II), Cd(II), Co(II), Fe(III), Ni(II)), were evaluated. For the most active complexes, cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and normal cell line HaCaT, as well as generation of reactive oxygen species (ROS), was tested.

Helicobacter pylori gastric infection in patients with laryngeal cancer and chronic laryngitis.

BACKGROUND: The purpose of this study was to investigate the pathohistological status of mucous lining infected with Helicobacte pylori as the possible cause of chronic laryngitis and laryngeal carcinoma. MATERIALS AND METHODS: The prospective examination included 51 patients suffering from planocellular laryngeal cancer and 26 examinees suffering from chronic laryngitis. The examinees and the control group were subjected to esophagogastroduodenoscopy which described the local status of the esophagus and stomach. Two biopsy samplings are taken from the stomach antrum and corpus. One part of the biopsies was colored using the histological technique used in the pathohistological detection of H. pylori, while the other part was incorporated in paraffin cubes where the H. Pylori gene expression was determined using the deparaffinization and PCR method DNA isolation. RESULTS: In the group of examinees suffering from laryngeal tumor, there were a higher number of patients suffering also from chronic gastritis (32/51) than in the other group, suffering from chronic laryngitis (9/26). In the chronic laryngitis group, there were more examinees with acute gastritis (12/26) than in the examined group (11/51). The difference is statistically significant (p = 0.0457). CONCLUSION: Chronic gastritis and H. pylori infection are risk factors for laryngeal carcinoma formation; therefore, acute gastritis with helicobacter pylori infection must be immediately treated to not let infection to become chronic.

COMPARISON OF DIFFERENT OUT-OF-HOSPITAL AIRWAY MANAGEMENT TECHNIQUES IN PATIENTS WITH CARDIAC ARREST IN SLAVONIA REGION.

Endotracheal intubation is the gold standard in inpatient treatment of cardiac arrest patients; however, there are conflicting research results in out-of-hospital conditions. This prospective study included 92 patients with confirmed cardiac arrest occurring outside a hospital facility, who fulfilled the inclusion criteria and whom the emergency ambulance team reached within 20 minutes from the event. Medical data on each patient (age, gender, cause of arrest, estimated time of arrest, time to arrival of the ambulance team, resuscitation commenced prior to arrival of the ambulance team, initial electrocardiographic rhythm, method of airway management, and success of resuscitation) were recorded. The airway maintenance techniques applied in the patients were endotracheal intubation and I-gel laryngeal mask (LMA). The rate of spontaneous circulation recovery resulting from different techniques of airway management and the incidence of spontaneous circulation recovery between the defibrillation rhythm and non-defibrillable rhythm groups were recorded for each patient. Forty-seven patients received endotracheal tube and the rest of 45 patients I-gel LMA treatment. The ratio of achieving spontaneous circulation with intubation versus I-gel LMA was 13 (28%) to 11 (24%) (p=0.725). The best return of spontaneous circulation results was recorded in patients suffering from ventricular fibrillation; however, there was no statistically significant difference between the intubation and I-gel LMA treatments (8 (47%) vs. 7 (41%); p=0.916). No statistically significant difference was observed between the outcomes of patients resuscitated by endotracheal intubation and I-gel LMA methods either.

Mahonia aquifolium Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro.

Mahonia aquifolium and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell-cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, M. aquifolium extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in MMP9 expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic M. aquifolium extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues.

Association of uPA and PAI-1 tumor levels and 4G/5G variants of PAI-1 gene with disease outcome in luminal HER2-negative node-negative breast cancer patients treated with adjuvant endocrine therapy.

BACKGROUND: The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated. PATIENTS AND METHODS: This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy. Determination of uPA and PAI-1 concentrations in the breast cancer tissue extracts was performed using FEMTELLE® uPA/PAI-1 ELISA. An insertion (5G)/deletion (4G) polymorphism at position - 675 of the PAI-1 gene was detected by PCR-RFLP analysis. RESULTS: Our research showed that patients with uPA tumor tissue levels higher than 3 ng/mg of protein had significantly reduced disease-free survival (DFS) and overall survival (OS) when compared to patients with uPA tumor tissue levels lower or equal to 3 ng/mg of protein. Patients with PAI-1 tumor tissue levels higher than 14 ng/mg of protein had significantly decreased OS in comparison with patients with PAI-1 tumor tissue levels lower or equal to 14 ng/mg of protein. ROC analysis confirmed the uPA and PAI-1 discriminative potential for the presence/absence of relevant events in these patients and resulted in higher cut-off values (5.65 ng/mg of protein for uPA and 27.10 ng/mg of protein for PAI-1) than standard reference cut-off values for both biomarkers. The prognostic importance of uPA and PAI-1 ROC cut-off values was confirmed by the impact of uPA higher than 5.65 ng/mg of protein and PAI-1 higher than 27.10 ng/mg of protein on poorer DFS, OS and event-free survival (EFS). We observed that patients with dominant allele in PAI-1 genotype (heterozygote and dominant homozygote, - 675 4G/5G and - 675 5G/5G) had significantly increased DFS, OS and EFS when compared with patients with recessive homozygote genotype (- 675 4G/4G). CONCLUSION: Our study indicates that uPA and PAI-1 tumor tissue levels and 4G/5G variants of PAI-1 gene might be of prognostic significance in early node-negative luminal HER2-negative breast cancer patients treated with adjuvant endocrine therapy.

Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels.

In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography.

Highly selective anthraquinone-chalcone hybrids as potential antileukemia agents.

A series of 23 novel anthraquinone-chalcone hybrids containing amide function was synthesized and structurally characterized. Sixteen compounds exerted strong cytotoxic activities against K562, Jurkat and HL-60 leukemia cell lines and significantly lower cytotoxic effects against normal MRC-5 cells, indicating very high selectivity in their anticancer action. The compounds 6g, 6u and 6v activate apoptosis in K562 cells through the extrinsic and intrinsic apoptotic pathway. The compound 6e triggered apoptosis in K562 cells only through the extrinsic apoptotic pathway. Treatment of K562 cells with each of these four compounds caused decrease in the expression levels of MMP2, MMP9, and VEGF, suggesting their anti-invasive, antimetastatic and antiangiogenic properties. The compounds 6g and 6v downregulated expression levels of miR-155 in K562 cells, while compounds 6e and 6u upregulated miR-155 levels in treated cells, in comparison with control cells. The structure-based 3-D QSAR models for 6f, 6e, 6i and 6l describe pro-apoptotic activity against caspase-3.

Synthesis, antioxidant and antiproliferative activities of 1,3,4-thiadiazoles derived from phenolic acids.

Two 2-amino-1,3,4-thiadiazoles containing phenolic hydroxyl groups were combined with different carboxylic acid chlorides giving sixteen amide derivatives with good antioxidant and antiproliferative potential. The compound 3'c with an adamantane ring displayed excellent DPPH radical scavenging activity and good cytotoxic activity against human acute promyelocytic leukemia HL-60 cells, while 1,3,4-thiadiazole 3'h with 4-chlorophenyl moiety was found to be the most effective in inhibition of survival of lung carcinoma A549 cells. All examined thiadiazoles except 3a and 3'a exerted higher cytotoxic activities on A549 and HL-60 cancer cells when compared with normal fibroblasts MRC-5, pointing to selectivity in their antiproliferative action. Some of the most active novel compounds 3c, 3'c, 3'g and 3'h induced significant increase in the percentage of HL-60 cells in the subG1 cell cycle phase in comparison with the control cells. The induction of cell death in HL-60 cells by these compounds was at least partially dependent on activation of caspase-3 and caspase-8. The compounds 3c and 3'c exerted strong antiangiogenic activity. Furthermore, compounds 3c, 3'c, 3'g and 3'h showed the ability to down-regulate the MMP2 and VEGFA expression levels in the treated HL-60 cells when compared with the control cell samples.

Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis.

BACKGROUND: Dipeptidyl peptidase IV (DPPIV/CD26) plays an important role in T cell activation and immune regulation, however the role of this enzyme in early rheumatoid arthritis (eRA) has not been clearly defined. The aim of this study was to determine the serum activity of DPPIV, its expression on peripheral blood mononuclear cells (PBMC) and to examine possible correlations with disease activity (DAS28) in untreated patients with eRA. METHODS: The study included 50 patients newly diagnosed with RA, who had not received any corticosteroid or disease modifying antirheumatic drugs (DMARD) therapy and whose conventional radiographs of hands and feet showed no structural damage. The control group consisted of 40 healthy volunteers. Also, 30 patients with chronic RA (cRA) were examined. The serum activity of DPPIV was determined by the direct photometric method, while expression of CD26 on PBMC was determined using flow cytometry. RESULTS: Decreased DPPIV serum activity was detected in patients with eRA and cRA compared to the control group (p=0.024, p<0.0001, respectively). Although, the percentage of overall CD26+ white blood cells (WBC) was significantly decreased in eRA patients (p<0.001), the percentage of CD26+ lymphocytes and monocytes and mean fluorescence intensity of CD26 on these cells in eRA patients showed no significant difference compared to healthy volunteers. DAS28 showed no significant correlation with CD26 expression or DPPIV serum activity, but a significant inverse correlation between the duration of symptoms and DPPIV serum activity was observed. CONCLUSIONS: Our results show that a decrease in DPPIV serum activity, but not CD26 expression, is present in an early stage of rheumatoid arthritis.

Identification of Phenolic Compounds from Seed Coats of Differently Colored European Varieties of Pea (Pisum sativum L.) and Characterization of Their Antioxidant and In Vitro Anticancer Activities.

To date little has been done on identification of major phenolic compounds responsible for anticancer and antioxidant properties of pea (Pisum sativum L.) seed coat extracts. In the present study, phenolic profile of the seed coat extracts from 10 differently colored European varieties has been determined using ultrahigh-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometer technique. Extracts of dark colored varieties with high total phenolic content (up to 46.56 mg GAE/g) exhibited strong antioxidant activities (measured by 2,2-diphenyl-1-picrylhydrazyl or DPPH assay, and ferric ion reducing and ferrous ion chelating capacity assays) which could be attributed to presence of gallic acid, epigallocatechin, naringenin, and apigenin. The aqueous extracts of dark colored varieties exert concentration-dependent cytotoxic effects on all tested malignant cell lines (human colon adenocarcinoma LS174, human breast carcinoma MDA-MB-453, human lung carcinoma A594, and myelogenous leukemia K562). Correlation analysis revealed that intensities of cytotoxic activity of the extracts strongly correlated with contents of epigallocatechin and luteolin. Cell cycle analysis on LS174 cells in the presence of caspase-3 inhibitor points out that extracts may activate other cell death modalities besides caspase-3-dependent apoptosis. The study provides evidence that seed coat extracts of dark colored pea varieties might be used as potential cancer-chemopreventive and complementary agents in cancer therapy.

Neuroprotective coordination of cell mitophagy by the ATPase Inhibitory Factor 1.

The mitochondrial ATPase Inhibitory Factor 1 (hereafter referred to as IF1) blocks the reversal of the F1Fo-ATPsynthase to prevent detrimental consumption of cellular ATP and associated demise. Herein, we infer further its molecular physiology by assessing its protective function in neurons during conditions of challenged homeostatic respiration. By adopting in vitro and in vivo protocols of hypoxia/ischemia and re-oxygenation, we show that a shift in the IF1:F1Fo-ATPsynthase expression ratio occurs in neurons. This increased IF1 level is essential to induce accumulation of the PTEN-induced putative kinase 1 (PINK-1) and recruitment of the mitophagic ubiquitin ligase PARK-2 to promote autophagic "control" of the mitochondrial population. In IF1 overexpressing neurons ATP depletion is reduced during hypoxia/ischemia and the mitochondrial membrane potential (ΔYm) resilient to re-oxygenation as well as resistant to electrogenic, Ca(2+) dependent depolarization. These data suggest that in mammalian neurons mitochondria adapt to respiratory stress by upregulating IF1, which exerts a protective role by coordinating pro-survival cell mitophagy and bioenergetics resilience.

Antiproliferative and antibacterial activity of some glutarimide derivatives.

Antiproliferative and antibacterial activities of nine glutarimide derivatives (1-9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9-27 µM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6-8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10(-3 )mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

Controlled and Impaired Mitochondrial Quality in Neurons: Molecular Physiology and Prospective Pharmacology.

Tuned mitochondrial physiology is fundamental for qualitative cellular function. This is particularly relevant for neurons, whose pathology is frequently associated with mitochondrial deficiencies. Defects in mitochondria are indeed key features in most neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). When mitochondrial coupling impairs, so does cell metabolism, trafficking and the signaling depending on the homeostasis of the mitochondrial network. Moreover, the quality control of mitochondria - via the process of mitochondrial autophagy - results biased in neurodegeneration stemming major interest on the molecular determinants of this process among neuroscientists. In this review, we highlight the most notable and acknowledged deficiencies of mitochondrial function and their relationship with diseases occurring in neurons and their transmission. The physiological aspects of mitochondrial biology in relation to bio-energy, dynamics and quality control will be discussed with the finality to form a comprehensive picture of the mitochondrial contribution to the pathophysiology of neurodegenerative syndromes. In this way we aim to set the scene to conceive novel strategies to better diagnose and target these debilitative conditions.

Synthesis and biological activity of amino acid derivatives of avarone and its model compound.

A series of eighteen derivatives of marine sesquiterpene quinone avarone and its model system tert-butylquinone with amino acids has been synthesized by nucleophilic addition of amino acids to the quinones. In vitro cytotoxic activity toward human cancer cell lines (HeLa, A549, Fem-X, K562, MDA-MB-453) and normal MRC-5 cell line was determined. Several compounds showed very strong inhibitory activity with IC50 values less than 10 µM. Avarone derivatives were more active than the corresponding tert-butylquinone derivatives. The results of the cytofluorimetric analysis of cell cycle of HeLa cells showed that apoptosis might be one of possible mechanism of action of these compounds in cancer cells. In order to examine the influence of caspases on cell death, the apoptotic mechanisms induced by the tested compounds were determined using specific caspases 3, 8 and 9 inhibitors. For all compounds antibacterial activities against six strains of Gram-positive and four strains of Gram-negative bacteria were determined, as well as antifungal activity against three fungal species.

Novel anthraquinone based chalcone analogues containing an imine fragment: synthesis, cytotoxicity and anti-angiogenic activity.

A new class of imine derivatives of hybrid chalcone analogues containing anthraquinone scaffold was synthesized and evaluated for their in vitro cytotoxic activity against HeLa, LS174, and A549 cancer cells. The compound 5n with furan ring linked to imino group showed potent activity against all target cells with IC50 values ranging from 1.76 to 6.11µM. A mode of action study suggested that compounds induced changes typical for apoptosis in HeLa cells. The most active compounds inhibited tubulogenesis and 5h was found to exhibit a strong anti-angiogenic effect.