Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine

This is an open access article under the CC BY-NC-ND license - http://creativecommons.org/licenses/by-nc-nd/4.0/

Synthesis and antibacterial profile of novel azomethine derivatives of β-phenylacrolein moiety

Purpose: To develop some novel molecules effective against antibiotic-resistant bacterial infections. Methods: A series of azomethines (SB-1 to SB-6) were synthesized from β-phenyl acrolein moiety. The structures of the synthesized compounds were confirmed on the basis of their UV ultra-violet (UV) spectroscopy (λmax: 200 - 400 nm), Fourier transform infra-red (FTIR, vibrational frequency: 500-4000 cm-1), 1H nuclear magnetic resonance (NMR, chemical shift: 0 - 10 ppm), 13C NMR (chemical shift: 0 - 200 ppm), mass spectrometry (m/z values: 0 - 500) and carbon hydrogen nitrogen (CHN) elemental analysis. The new compounds were screened for antibacterial activity by test-tube dilution and disc diffusion methods using gentamicin as reference standard. Results: The structures of azomethine were in full agreement with their spectral data. Among all the synthesized compounds, compounds SB-5 and SB-6 exhibited the highest minimum inhibitory concentration (MIC) of 62.5 μg/mL. At MIC of 250 μg/mL, all compounds SB-1 to SB-6 displayed significant antibacterial activity, compared to gentamycin (p < 0.05). SB-5 and SB-6 were active against S. aureus, P. aeruginosa and K. pneumoniae; SB-3 was active against B. subtilis and S. aureus. SB-4 was active against P. aeruginosa and S. aureus while SB-1 and SB-2 were active against S. aureus. Conclusion: The synthesized compounds possess antibacterial activities compared to those of gentamycin.

Antitumor activity of doxorubicine-loaded nanoemulsion against Ehrlich ascites carcinoma-bearing mice

Purpose: To evaluate the antitumor activity of doxorubicine (DOX)-loaded nanoemulsion (NE) on Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. Methods: The mice were divided into five groups (n = 20) according to the administered drug. Groups I - V were labeled as negative control (normal), positive control of the untreated EAC bearing mice (EAC control), blank nanoemulsion (BI-NE), DOX-loaded-NE (DOX/LNE) and free DOX (DOX-Sol), respectively. Cardiotoxicity was assessed by measuring changes in body and organ weight, analyzing serum enzymes and lipids, and examining histological changes in heart tissues by light microscopy. In addition, mean survival time (MST), increase in life span (ILS) and survival (S) of the mice were determined. Results: DOX/LNE group reduced levels of serum enzymes and lowered damage to heart tissues relative to DOX-Sol group. The MST of the DOX/LNE group (80 ± 0.0 days) was significantly greater than that for DOX-Sol group (34.6 ± 8.9 days), while ILS of DOX/LNE (265.30 days) was higher than that of DOX-Sol (57.99 days) by 4.6-fold. Conclusion: Administration of DOX/LNE to EAC-bearing mice improves the efficacy of DOX and reduce its side effects on the heart.

Phytochemical profile and some biological activities of three Centaurea species from Turkey

Purpose: To characterise the phytochemical profile of whole plants of Centaurea balsamita, C. depressa and C. lycopifolia with LC-ESI-MS/MS, and as well as their antioxidant, anticholinesterase and antimicrobial activities. Methods: Organic and aqueous extracts of the three Centaurea species were evaluated for DPPH free radical, ABTS cation radical scavenging and cupric reducing antioxidant capacity (CUPRAC). Acetyland butyryl-cholinesterase enzyme inhibition abilities of the extracts using petroleum ether, acetone, methanol and water were studied to determine anticholinesterase activity, while antimicrobial activity was determined by disc diffusion method using appropriate antimicrobial standards and organisms. The phytochemical components of the methanol extracts were assessed by LC-MS/MS. Results: The methanol extract of C. balsamita exhibited much higher DPPH free and ABTS cation radicals scavenging activities (with IC50 of 62.65 ± 0.97 and 24.21 ± 0.70 mg/ml, respectively) than the other extracts. The petroleum ether extracts of the plant species exhibited moderate inhibitory activity against butyrylcholinesterase enzymes while the acetone extract of C. balsamita showed good antifungal activity against Candida albicans. Quinic acid (17513 ± 813 μg/g, 63874 ± 3066 μg/g and 108234 ± 5195 μg/g) was the major compound found in the methanol extracts of C. balsamita, C. depressa and C. Lycopifolia, respectively. Conclusion: These results indicate quinic acid is the major compound in the three plant species and that Centaurea balsamita has significant antioxidant, anticholinesterase and antimicrobial properties. Further studies to identify the compounds in the extracts responsible for the activities are required.

Exploring the relationship between patterns of physical activity, sedentary behaviour and cardiometabolic health in middle-aged Irish adults

Background and Study Rationale Being physically active is a major contributor to both physical and mental health. More specifically, being physically active lowers risk of coronary heart disease, high blood pressure, stroke, metabolic syndrome (MetS), diabetes, certain cancers and depression, and increases cognitive function and wellbeing. The physiological mechanisms that occur in response to physical activity and the impact of total physical activity and sedentary behaviour on cardiometabolic health have been extensively studied. In contrast, limited data evaluating the specific effects of daily and weekly patterns of physical behaviour on cardiometabolic health exist. Additionally, no other study has examined interrelated patterns and minute-by-minute accumulation of physical behaviour throughout the day across week days in middle-aged adults. Study Aims The overarching aims of this thesis are firstly to describe patterns of behaviour throughout the day and week, and secondly to explore associations between these patterns and cardiometabolic health in a middle-aged population. The specific objectives are to: 1 Compare agreement between the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and GENEActiv accelerometer-derived moderate-to-vigorous (MVPA) activity and secondly to compare their associations with a range of cardiometabolic and inflammatory markers in middle-aged adults. 2 Determine a suitable monitoring frame needed to reliably capture weekly, accelerometer-measured, activity in our population. 3 Identify groups of participants who have similar weekly patterns of physical behaviour, and determine if underlying patterns of cardiometabolic profiles exist among these groups. 4 Explore the variation of physical behaviour throughout the day to identify whether daily patterns of physical behaviour vary by cardiometabolic health. Methods All results in this thesis are based on data from a subsample of the Mitchelstown Cohort; 475 (46.1% males; mean aged 59.7±5.5 years) middle-aged Irish adults. Subjective physical activity levels were assessed using the IPAQ-SF. Participants wore the wrist GENEActiv accelerometer for 7 consecutive days. Data was collected at 100Hz and summarised into a signal magnitude vector using 60s epochs. Each time interval was categorised based on validated cut-offs. Data on cardiometabolic and inflammatory markers was collected according to standard protocol. Cardiometabolic outcomes (obesity, diabetes, hypertension and MetS) were defined according to internationally recognised definitions by World Health Organisation (WHO) and Irish Diabetes Federation (IDF). Results The results of the first chapter suggest that the IPAQ-SF lacks the sensitivity to assess patterning of activity and guideline adherence and assessing the relationship with cardiometabolic and inflammatory markers. Furthermore, GENEActiv accelerometer-derived MVPA appears to be better at detecting relationships with cardiometabolic and inflammatory markers. The second chapter examined variations in day-to-day physical behaviour levels between- and within-subjects. The main findings were that Sunday differed from all other days in the week for sedentary behaviour and light activity and that a large within-subject variation across days of the week for vigorous activity exists. Our data indicate that six days of monitoring, four weekdays plus Saturday and Sunday, are required to reliably estimate weekly habitual activity in all activity intensities. In the next chapter, latent profile analysis of weekly, interrelated patterns of physical behaviour identified four distinct physical behaviour patterns; Sedentary Group (15.9%), Sedentary; Lower Activity Group (28%), Sedentary; Higher Activity Group (44.2%) and a Physically Active Group (11.9%). Overall the Sedentary Group had poorer outcomes, characterised by unfavourable cardiometabolic and inflammatory profiles. The remaining classes were characterised by healthier cardiometabolic profiles with lower sedentary behaviour levels. The final chapter, which aimed to compare daily cumulative patterns of minute-by-minute physical behaviour intensities across those with and without MetS, revealed significant differences in weekday and weekend day MVPA. In particular, those with MetS start accumulating MVPA later in the day and for a shorted day period. Conclusion In conclusion, the results of this thesis add to the evidence base regards an optimal monitoring period for physical behaviour measurement to accurately capture weekly physical behaviour patterns. In addition, the results highlight whether weekly and daily distribution of activity is associated with cardiometabolic health and inflammatory profiles. The key findings of this thesis demonstrate the importance of daily and weekly physical behaviour patterning of activity intensity in the context of cardiometabolic health risk. In addition, these findings highlight the importance of using physical behaviour patterns of free-living adults observed in a population-based study to inform and aid health promotion activity programmes and primary care prevention and treatment strategies and development of future tailored physical activity based interventions.

TECTONIC CONTROLS ON FLUVIAL LANDSCAPE DEVELOPMENT IN CENTRAL-EASTERN PORTUGAL: INSIGHTS FROM LONG PROFILE TRIBUTARY STREAM ANALYSES

This study examines the long profiles of tributaries of the Tejo (Tagus) and Zêzere rivers in central eastern Portugal (West Iberia) in order to provide new insights into the patterns, timing and controls on drainage development during the Pleistocene to Holocene incision stage. The long profiles were extracted from lower order tributary streams associated with the trunk drainage of the Tejo River and one main tributary, the Zêzere River (Fig. 1). These streams flow through a landscape strongly influenced by variations in bedrock lithology (mainly granites and metasediments), fault structures delimiting crustal blocks with distinct uplift rates, and a base-level lowering history (tectonic uplift / eustatic). The long profiles of the tributaries of the Tejo and Zêzere rivers record a series of transient and permanent knickpoints. The permanent knickpoints have direct correlation with the bedrock strength, corresponding to the outcropping of very hard quartzites or to the transition from softer (slates/metagreywaques) to harder (granite) basement. The analyzed streams/rivers record also an older transient knickpoint/knickzone separating: a) an upstream relict graded profile, with lower steepness and higher concavity, that reflects a long period of quasi-equilibrium conditions reached after the beginning of the incision stage; and b) a downstream reach displaying a rejuvenated long profile, with steeper gradient and lower concavity, particularly for the final segment, which is often convex (Fig. 2). The rejuvenated reaches testify the upstream propagation of several incision waves that are the response of each stream to continuous or increasing crustal uplift and dominant periods of base-level lowering by the trunk drainages, coeval of low sea level conditions. The long profiles and their morphological configurations enabled spatial and relative temporal patterns of incision to be quantified for each individual tributary stream. The incision values of streams flowing in uplifted blocks of the Portuguese Central Range (PCR) (ca.380-280 m) indicate differential uplift and are higher than the incision values of streams flowing on the adjacent South Portugal planation surface – the Meseta (ca. 200 m). The normalized steepness index, calculated using the method of Wobus et al. (2006), proved to be sensitive to active tectonics, as lower ksn values were found in relict graded profiles of streams located in less uplifted blocks, (e.g. Sertã stream in the PCR), or in those flowing through tectonic depressions. Fig. 1 – Geological map of the study area. 1 – fluvial terraces (Pleistocene); 2 – sedimentary cover (Paleogene and Neogene); 3 – slates and metasandstones (Devonian); 4 – slates and quartzites (Silurian); 5 – quartzites (Ordovician); 6 – slates and metagreywackes (Precambrian to Cambrian); 7 – slates, metagreywackes and limestones (Precambrian); 8 – granites and ortogneisses; 9 – diorites and gabros; 10 - fault. SFf – Sobreira Formosa fault; Sf – Sertã fault; Pf – Ponsul fault; Gf – Grade fault. The differential uplift indicated by the distribution of the ksn values and by the fluvial incision was likely accumulated on a few major faults, as the Sobreira Formosa fault (SFf), thus corroborating the tectonic activity of these faults. Due to the fact that the relict graded profiles can be correlated with other geomorphic references documented in the study area, namely the T1 terrace of the Tagus River (with an age of ca. 1 Myr), the following incision rates can be estimated: a) for the studied streams located in uplifted blocks of the PCR, 0.38 m/kyr to 0.28 m/kyr; b) for the streams flowing on the South Portugal planation surface, 0.20 m/kyr. The differential uplift inferred between crustal blocks in the study area corroborates the neotectonic activity of the bordering faults, which has been proposed in previous studies based upon less robust data. Fig. 2 – Longitudinal profile of the Nisa stream a tributary of the Tejo River. Note the equilibrium relict profile upstream the older transient knickpoint (hatched line) and the downstream rejuvenated profile (continuous line). Legend: tKP – transient knickpoint; rKp – resistant knickpoint; Mt – schist and phyllite; Gr – granite; Hf – hornfels; Og – orthogneisse. In the inset Distance – Slope plots, fill circles correspond to the relict graded profile, crosses correspond to the rejuvenated profile located downstream the older transient knickpoint (tKP).

Impact of salt reduction on biogenic amines, fatty acids, microbiota, texture and sensory profile in traditional blood dry-cured sausages

Meat industry needs to reduce salt in their products due to health issues. The present study evaluated the effect of salt reduction from 6% to 3% in two Portuguese traditional blood dry-cured sausages. Physicochemical and microbiological parameters, biogenic amines, fatty acids and texture profiles and sensory panel evaluations were considered. Differences due to salt reduction were perceptible in a faint decline of water activity, which slightly favoured microbial growth. Total biogenic amines content ranged from 88.86 to 796.68 mg kg 1 fresh matter, with higher amounts, particularly of cadaverine, histamine and tyramine, in low-salt products. Still, histamine and other vasoactive amines remained at low levels, thus not affecting consumers’ health. Regarding fatty acids, no significant differences were observed due to salt. However, texture profile analysis revealed lower resilience and cohesiveness in low-salt products, although no textural changes were observed by the sensory panel. Nevertheless, low-salt sausages were clearly preferred by panellists.

Tectonic and lithological controls on fluvial landscape development in central-eastern Portugal: Insights from long profile tributary stream analyses

This study examines the long profiles of tributaries of the Tagus and Zêzere rivers in Portugal (West Iberia) in order to provide new insights into patterns, timing, and controls on drainage development during the Quaternary incision stage. The studied streams are incised into a relict culminant fluvial surface, abandoned at the beginning of the incision stage. The streams flow through a landscape with bedrock variations in lithology (mainly granites and metasediments) and faulted blocks with distinct uplift rates. The long profiles of the analyzed streams record an older transitory knickpoint/knickzone separating (1) an upstream relict graded profile, with lower steepness and higher concavity, that reflects a long period of quasi-equilibrium conditions reached after the beginning of the incision stage, and (2) a downstream rejuvenated long profile, with steeper gradient and lower concavity, particularly for the final reach, which is often convex. The rejuvenated reaches testify to the upstream propagation of several incision waves, interpreted as the response of each stream to increasing crustal uplift and prolonged periods of base-level lowering by the trunk drainages, coeval with low sea level conditions. The morphological configurations of the long profiles enabled spatial and relative temporal patterns of incisions to be quantified. The incision values of streams flowing on the Portuguese Central Range (PCR; ca. 380–150 m) are variable but generally higher than the incision values of streams flowing on the adjacent South Portugal Planation Surface (SPPS; ca. 220–110 m), corroborating differential uplift of the PCR relative to the SPPS. Owing to the fact that the relict graded profiles can be correlated with the Tagus River T1 terrace (1.1–0.9 My) present in the study area, incision rates can be estimated (1) for the streams located in the PCR, 0.38–0.15 m/ky and (2) for the streams flowing on the SPPS, 0.22–0.12 m/ky. The differential uplift inferred in the study area supports the neotectonic activity of the bordering faults, as proposed in previous studies based upon other geological evidence.

Evaluation of the evolution of the anthocyanins profile in red wine grape varieties in Alentejo

The flavonoids (including anthocyanins) are wine compounds with important anti-oxidant activity, protecting the cells against oxidative processes, preventing cardiovascular and neurodegenerative diseases, cancer, among others (Antoniolli et al. 2015; Castañeda-Ovando et al. 2009; Hosu et al. 2014; Huang et al. 2009; Kong et al. 2003). Anthocyanins in grapes at harvest are determinant to red wine quality and their development in the grape must be characterised in order to determine the most suitable date for the harvest. Thus the aim of this research is the evaluation of anthocyanins composition in two red wine grape varieties from véraison continuing through ripening. Anthocyanins were quantified by high resolution liquid chromatography (HPLC-DAD). Additionally, the total phenols content were quantified by UV-Vis Spectrometry. The anthocyanins’ profile evolution may be dependent on the variety and ripening phase. During ripening grape samples have shown an increase of coumaryl derivatives. This information may lead us to understand the anthocyanins biosynthesis pathway in different grape varieties. The development of anthocyanins from the véraison seems to follow a pattern that coincides with the increasing accumulation of soluble sugars.

Tectonic and lithological controls on fluvial landscape development in central-eastern Portugal: Insights from long profile tributary stream analyses

This study examines the long profiles of tributaries of the Tagus and Zêzere rivers in Portugal (West Iberia) in order to provide new insights into patterns, timing, and controls on drainage development during the Quaternary incision stage. The studied streams are incised into a relict culminant fluvial surface, abandoned at the beginning of the incision stage. The streams flow through a landscape with bedrock variations in lithology (mainly granites and metasediments) and faulted blocks with distinct uplift rates. The long profiles of the analyzed streams record an older transitory knickpoint/knickzone separating (1) an upstream relict graded profile, with lower steepness and higher concavity, that reflects a long period of quasi-equilibrium conditions reached after the beginning of the incision stage, and (2) a downstream rejuvenated long profile, with steeper gradient and lower concavity, particularly for the final reach, which is often convex. The rejuvenated reaches testify to the upstream propagation of several incision waves, interpreted as the response of each stream to increasing crustal uplift and prolonged periods of base-level lowering by the trunk drainages, coeval with low sea level conditions. The morphological configurations of the long profiles enabled spatial and relative temporal patterns of incisions to be quantified. The incision values of streams flowing on the Portuguese Central Range (PCR; ca. 380–150 m) are variable but generally higher than the incision values of streams flowing on the adjacent South Portugal Planation Surface (SPPS; ca. 220–110 m), corroborating differential uplift of the PCR relative to the SPPS. Owing to the fact that the relict graded profiles can be correlated with the Tagus River T1 terrace (1.1–0.9 My) present in the study area, incision rates can be estimated (1) for the streams located in the PCR, 0.38–0.15 m/ky and (2) for the streams flowing on the SPPS, 0.22–0.12 m/ky. The differential uplift inferred in the study area supports the neotectonic activity of the bordering faults, as proposed in previous studies based upon other geological evidence.

6-(Methylsulfonyl) hexyl isothiocyanate as potential chemopreventive agent: molecular and cellular profile in leukaemia cell lines

Despite numerous therapeutic interventions cancer is still today the second leading cause of death. A growing interest has been addressed to isothiocytanates and more recently, the 6- (methylsulfonyl) hexyl isothiocyanate (6-MITC), the main constituent of the rhizome of Wasabia Japonica, has stimulated the interest of researchers. Aim of the research was to study if 6-MITC is able to modulate the main mechanisms underlying chemopreventive process in leukemic cells lines, verify the selectivity of action and the safety of use in terms of mutagenicity. The study was conducted on different cell types. In particular, Jurkat and HL-60 cells were treated with increasing concentrations of 6-MITC and cell viability, induction of apoptosis, cell cycle analysis, autophagy modulation and stimulation of differentiation were evaluated by flow cytometry. PBL, the non-transformed counterparty of leukemia cells, was used to analyse the selectivity of action by studying the same mechanisms previously indicated. Finally, safety of use and antimutagenicity were studied in TK6 cells adopting an automated protocol in flow cytometry. The achieved results have demonstrated that isothiocyanate modulates many signaling pathways involved in chemopreventive mechanism. In fact, 6-MITC induces apoptosis of both transformed cells, limits tumor growth by slowing down the cell cycle of Jurkat cells and blocks HL-60 cell cycle, increases the autophagic flux and induces cytodifferentiation of promyelocytic HL-60 into macrophage and granulocytic phenotypes. Furthermore, the results obtained with 6-MITC on PBL from healthy donors suggest that the isothiocyante is a good selective cytotoxic agent. Essential feature of a good chemopreventive agent is selectivity toward cancer cells and low toxicity towards non-transformed cells. Finally, the analysis of the micronuclei revealed that 6-MITC is not mutagenic, ensuring safe use, and that instead, it is able to counteract the mutagenic activity of the aneuploidogen Vinblastine, demonstrating another important and interesting chemopreventive activity.

EBV Type II latency relies on PARP1 activity and is essential for gastric epithelial cell transformation in EBV-associated Gastric Cancer (EBVaGC)

Epstein-Barr virus (EBV) establishes a lifelong asymptomatic infection by replicating its chromatinized genome, called episome, together with the host genome. EBV exhibits different latency-associated transcriptional repertoires that mirror its three-dimensional structures of the genome. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents almost 10% of all gastric cancers globally. EBVaGC exhibit an intermediate viral transcription profile known as "Latency II", expressing specific viral genes and non-coding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed a destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and consequently, an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II, and III latencies display different 3D episomal structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched chromatin interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV episomes at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation.

Profile Of The Use Of Disease Modifying Drugs In The Brazilian Registry Of Spondyloarthritides.

Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). At least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Inhibitory Effects Of A Cured Antibacterial Bonding System On Viability And Metabolic Activity Of Oral Bacteria.

To evaluate the antimicrobial efficacy of Clearfil SE Protect (CP) and Clearfil SE Bond (CB) after curing and rinsed against five individual oral microorganisms as well as a mixture of bacterial culture prepared from the selected test organisms. Bacterial suspensions were prepared from single species of Streptococcus mutans, Streptococcus sobrinus, Streptococcus gordonii, Actinomyces viscosus and Lactobacillus lactis, as well as mixed bacterial suspensions from these organisms. Dentin bonding system discs (6 mm×2 mm) were prepared, cured, washed and placed on the bacterial suspension of single species or multispecies bacteria for 15, 30 and 60 min. MTT, Live/Dead bacterial viability (antibacterial effect), and XTT (metabolic activity) assays were used to test the two dentin system's antibacterial effect. All assays were done in triplicates and each experiment repeated at least three times. Data were submitted to ANOVA and Scheffe's f-test (5%). Greater than 40% bacteria killing was seen within 15 min, and the killing progressed with increasing time of incubation with CP discs. However, a longer (60 min) period of incubation was required by CP to achieve similar antimicrobial effect against mixed bacterial suspension. CB had no significant effect on the viability or metabolic activity of the test microorganisms when compared to the control bacterial culture. CP was significantly effective in reducing the viability and metabolic activity of the test organisms. The results demonstrated the antimicrobial efficacy of CP both on single and multispecies bacterial culture. CP may be beneficial in reducing bacterial infections in cavity preparations in clinical dentistry.

Identification Of Target Genes Using Gene Expression Profile Of Granulocytes From Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.