Littérature scientifique sur le sujet « Resistance to treatement »

The underdoped YBa 2 ( Cu 0.96 Fe 0.04)3 O y superconducting system has been prepared and investigated. The effect of oxygen content and the thermal treatment (fast quenching of underdoped samples from 250 K to 4.5 K) on the electrical resistance were studied. The semiconductor behaviour of electrical resistance after the fast quenching of the samples agree with a model for the stripe formation in Cu(2)O 2 plane. The presence of two resistive transitions (T c 1=18 K and T c2 =36 K ) were evidenced for y=6.75 sample. The disappearance of the low transition after the thermal treatment were analysed in relation with the role of Fe clusters on the order of apical oxygen. The decrease of T c by increasing oxygen deficiency was attributed to the fragmentation and stripe pinning in Cu(2)O 2 planes as a result of the disorder produced by the Fe clusters in Cu(1)O chains.

Abstract Deep neck infection is an infection in the potential space and fascial planes of the neck, either with abscess formation or cellulitis. Cervical fascias create space and plane, which define and limit the spread of infection. Danger space is the area of thin connective tissue extending from the skull base down to the diaphragm. This space is enclosed on all sides, therefore inflammation in this area arises from penetration and spreads of infection from surrounding structures. This risk is in the rapid spread of infection in the chest, due to the low resistance of thin connective tissue. Formation of the descending necrotizing mediastinitis is the most common and most feared complication of danger space. Authors describe a case of extensive dental infection that despite intensive surgical and antibiotic treatement spread to other anatomical areas and caused descending necrotizing mediastinitis.

Caries diagnosis should be done in the early stages in order to preserve long-term hard dental structures. In addition to that, the cavity lesions treatment should use adhesive materials for crown obturation which allow strictly carious lesion removal and do not require the creation of retention forms, involving an additional sacrifice of dental tissues, thus jeopardizing the tooth resistance. The study presents the case of a 9 years old, male patient who had multiple cavities in the mixed dentition. The designed treatment plan aimed, firstly, at assessing the degree of damage, trough cavities, of the four 6-year molars existing on the arcades and the choice of techniques and materials for coronal restoration following ART concept (Atraumatic Restorative Treatement). Cavities diagnosis was made by combining conventional methods (visual inspection, inspection and palpation by probe, retro alveolar radiography and OPG) and modern methods (laser fluorescence DIAGNOdent Pen 2190). The prime molars 36, 46 treatment consisted in the creation of some VI class cavities, than plugged with glassionomer cement (Fuji IX) due to increased and prolonged release of fluoride, while the 16, 26 molars treatment was achieved by incipient lesions remineralization by topical application of a fluoride varnish containing 5% sodium fluoride (Profluorid varnish, Voco GmbH).

This study was conducted to examine telomere biology in terms of improving insulin sensitivity in a type 2 diabetic animal model: Otsuka Long-Evans Tokushima fatty (OLETF) rats. To improve insulin sensitivity, pioglitazone (PG; 10 mg·kg−1·day−1) was administrated to OLETF rats from 20 to 40 wk of age, and the effects of treatment were compared with those in untreated OLETF or control Long-Evans Tokushima Otsuka fatty rats. At the end of the study, the homeostasis model assessment of insulin resistance significantly increased in OLETF rats but decreased in OLETF rats treated with PG. No shortening of telomere length was observed in the heart tissue of OLETF rats, whereas telomerase activity was decreased in OLETF heart tissue. The mRNA expression of both telomerase reverse transcriptase and telomere repeat binding factor 2 was downregulated in the hearts of OLETF rats. The protein expression of phospho-Akt, insulin-like growth factor, and endothelial nitric oxide synthase was reduced in OLETF rats. On the other hand, myocardial matrix metalloproteinase-9 expression was elevated in OLETF rats. The changes observed in OLETF rats were inhibited by PG treatment. However, protein and mRNA expression of Sirt1, a lifespan modulator, were attenuated in OLETF rat hearts, although they were enhanced in OLETF rats with PG treatement. Myocardial fibrosis was less extensive and diastolic dysfunction more greatly ameliorated in PG-treated OLETF rats than in OLETF rats. These findings suggest that improving insulin sensitivity via the activation of peroxisom proliferator-activated receptor-γ may exert regulatory effects on cardiac telomere biology and may have desirable morphological and functional effects on the diabetic heart.

Abstract Background: Reciprocal translocations like t(8;21) or inv(16) in acute myeloid leukemia (AML) usually predicts a good response to chemotherapy with a high remission rate and a relatively long median survival. MDR1/Pgp, the gene product of MDR1, is recognized as an important class of proteins for regulating pharmacokinetics. Several reports showed the effects of ABCB1 (mutidrug resistance 1 gene, MDR1, PgP) genotypes such as single nucleotide polymorphisms (SNPs) on pharmacotherapy in various malignancies including AML. However, it remains to be clarified that these SNPs of ABCB1 gene play an significant role in the treatment outcome of AML patients with favorable cytogenetics especially t(8;21) or inv(16). Aims: To determine the prevalence and the prognostic role of ABCB1 polymorphisms in de novo AML patients with t(8;21) or inv (16). Methods: Twenty ABCB1 gene polymorphisms (SNP numbers: rs1055302, rs1002205, rs4148750, rs7779562, rs6980101, rs1922242, rs2235013, rs4728702, rs1922240, rs1922241, rs4148734, rs6950978, rs10256836, rs1202172, rs17327442, rs7802773, rs13229143, rs4148732, rs1978095, rs10264856) were evaluated by performing DNA polymerase chain reaction assays on 49 bone marrow samples obtained at initial diagnosis from the AML patients with t(8;21) or inv(16). DNA sequencing and GeneScan analysis was performed to confirm the the genotyping results. All patients received one round of intensive induction chemotherapy consisting of 3 days of idarubicin and 7 days of cytarabine. Results: Of total 49 patients, 39 (79.6%) were AML with t(8;21) and 10(20.4%) were AML with inv(16). The median age of patients was 37 years (range, 17–69 years). There were 29 males (59.2%) and 20 females (40.8%). There was no statistically significant difference in age, gender, leukocyte count, and percentage of peripheral or bone marrow blasts in the patients according to the ABCB1 polymophisms or cytogenetic abnormalities. However, there was significant difference in complete response (CR) rate according to the zygocities of SNPs in the intron of ABCB1 gene such as rs6980101 (genotype C/C: 68.4% vs. C/T: 100%, p=0.03), rs10256836 (G/G: 91.3% vs. G/C: 50%, p=0.03), rs17327442 (T/T: 88.9% vs. T/A: :40%, p=0.01), rs4148732 (A/A: 95.8% vs. A/G: 50%, p=0.00). CR rates were not significantly influenced by cytogenetic abnormalities. There was no significant difference in relapse rate, leukemia-free survival and overall survival between homo- and heterozygote groups in these polymorphsims. Conclusions: This study revealed an association between ABCB1 SNPs and the treatement outcomes for AML patients with t(8;21) or inv(16). Further study is needed to reach the definite conclusion on these associations. However, a stratified treatment plan in remission induction chemotherapy such as augmentation or addition of other chemotherapeutic agents may be warranted for the AML with t(8;21) or inv(16) harvoring such ABCB1 polymophrisms.

Research has been initiated on the effects of high frequency peening methods on the fatigue strength. These methods combine an improvement of weld toe profile with an initiation of compressive residual stresses and surface hardening. The effects of two techniques, High Frequency Impact Treatment (HiFIT) and Ultrasonic Impact Treatemnt (UIT) are compared. Laser measurements of the weld seam prove that both methods increase the overall weld toe radii. Further, residual stress measurements verify the introduction of compressive residual stresses at least up to a depth of 1 mm. The values meet the yield strength combined with an increase of the surface hardness. These material mechanical effects cause an increased crack resistance. Crack detection methods prove that the material mechanical effects yield to a retarded crack initiation. Experimental results show that these effects lead to a significant increase of the fatigue strength and reduced slopes of the SN-curves.

The recycling of alumium alloys has been growing in interest and applications during the last fourthy years and has become a cost effective, ecological and reliable way to produce aluminium parts. The aluminium scraps that can be recycled include cans and machining chips. The machining processes produce chips of various sizes and shapes, wet or dry, oxidised or not, depending on type of process and the machining conditions, parameters and tools used. Some processes produce metallic dusts and fine chips while other produce large or medium size chips. In some industries such as mould making and aeronautic industries, the chip removal can easily represent 80% of the initial workpiece mass. The type of chips produced during machining can have a great impact on chip management, on part quality, on machine and tool reliability and on part manufacturing costs. The machining chips can be recycled using casting, sintering or pressing and extrusion processes depending on the goal targeted. The selection of the recycling process must take into account the targeted applications, the chip (composition, sizes and cleanliness) and its mechanical properties. Depending on the nature of process to be used and the machining chip generation conditions, some treatments might be necessary prior to transportation and recycling. Parts made with recycled chips can either be bi-phase metal matrix composites materials or usual one phase material with mechanical properties and wear properties comparable or not to the parent alloys. Over the last decades, several chip recycling processes have been proposed for aluminium alloys. This article review the aluminium chips formation, treatement methods, the recycling processes and their impact on recomposed parts’ performance: strength, ductility, corosion and wear resistances.

This study has investigated the effect of hydroperoxide treatment on the properties of bagasse fibers in order to get the value added material using by-products from sugar production such as reinforcement for composite materials. The results of processing bagasse fibers with hydroperoxide at different concentration, temperature and treatement time showed that treatment condition had a great influence on the properties of the obtained fibers. With the suitable treatement conditions of 10% peroxide concentration, treatment time of 40 minutes, treatment temperature at 60 0C, the treated fiber has a more homogeneous surface than the untreated. The composite using hybrid bagasse/glass fiber has higher flexural and impact resistance than when using glass fiber and reaches 162.6 MPa and 38.9 KJ/m2 (16.7% and 213% respectively compared to composite using glass fiber only). This can be explained that the treated bagasse fiber has better wetting ability with the matrix resin and together with the energy absorption capacity of the fiber bundle, it leads to an increase in flexural strength and impact strength of composite material.

Quorum sensing (QS) mechanism is cell communication that plays vital role in the development of infection by many pathogenic microorganisms. It controls multiple virulence factors such as pigmentation, biofilm formation, swarming motility, resistance towards antibiotics, extracellular polysaccharide production (EPS) and expression of several collective traits. The disruption of quorum sensing mechanism can be a solution to the emerging problem of multi-drug resistance among pathogenic bacteria. The effector molecule for Quorum sensing inhibition may be enzymatic or non- enzymatic in nature termed as Quorum Quenching (QQ) or Quorum sensing inhibitory (QSIs)/anti –QS compound, respectively. We used marine epibiotic bacteria as a source to obtained novel bacterial strain as QSI producer. One of the potent isolate, SJ4 was identified as Pseudomonas stutzeri SJ4, it is a short rod, gram negative bacterium. The ethyl acetate extract from P. stutzeri SJ4, showed highest QSI activity against monitor strain Chromobacterium violaceum (MTCC 5526). The extracted compound was tested against P. aeruginosa PAO1 at minimum inhibitiory concentration (MIC) and sub-MIC to study the effect on virulence factors. The significant inhibition of pycocyanin pigment, EPS production, rhamnolipid production and reduced swimming and swarming motility was observed. In addition, biofilm formation was notably inhibited which was confirmed by staining and spectometric method. Based on this observation, QS interption by extract which contain QSI remarkebly reduced the virulence of pathogen hence, can be use as therapeutic agents. The Thin Layer Chomatography (TLC) and Gas chrmoatography-Mass Spectrometry (GC-MS) identified major compound as n-Hexadecanoic acid. However, further research is required on purification of compound and its potential applications for the treatement of infections.

Environ 15 % des cancers du sein triple négatif (TNBC) sont déficients en BRCA et présentent un déficit de réparation de l'ADN par recombinaison homologue (HRD) et une sensibilité accrue aux traitements génotoxiques. Nous avons émis l'hypothèse que les TNBC BRCA-déficients sont très sensibles aux médicaments induisant un stress réplicatif, ce qui pourrait ouvrir de nouvelles perspectives thérapeutiques. Nos résultats montrent que les TNBC déficients en BRCA1 (BRCA1-Def), ainsi que les lignées cellulaires de cancer de l'ovaire BRCA1-Def, ont montrés une sensibilité accrue à la gemcitabine. De manière notable, la gemcitabine a induit une augmentation de la mort cellulaire dans les cellules BRCA1-Def, associée à une gestion perturbée du stress réplicatif. En effet, jusqu'à 80 % des cellules BRCA1-Def présentaient un marquage ɣH2AX persistant même 48 h après le lavage de la gemcitabine, par rapport à leur homologue de lignée BRCA1-WT dans laquelle le marquage diminue considérablement. De plus, les cellules BRCA1-Def traitées à la gemcitabine ont montré un déséquilibre persistant entre les cellules RPA32-positives et ɣH2Ax-positives, suggérant un stress réplicatif non résolu dans ces cellules et la survenue d'une catastrophe réplicative dans une fraction substantielle des cellules. En outre, une fraction importante de cellules ɣH2AX+ présentait un marquage pannucléaire, dont le nombre augmentait régulièrement au fil du temps dans les cellules BRCA1-Def traitées à la gemcitabine, alors qu'il diminuait dans les cellules BRCA1-WT. Fait intéressant, près de 90% des cellules pannucléaires ɣH2AX étaient complètement négatives pour RPA32 et présentaient un fort marquage BrdU dans des conditions non dénaturantes, indiquant une accumulation importante d'ADN simple brin spécifiquement dans ces cellules. De manière notable, un nombre important de cellules ɣH2Ax pannucléaire étaient également négatives pour les foyers RAD51, mais étaient positives pour les foyers 53BP1 et FANCD2. Le paysage opposé a été observé dans les cellules BRCA1-WT dans lesquelles les cellules ɣH2AX pannucléaires étaient RAD51+, 53BP1- et FANCD2-. Ces résultats indiquent une réponse aiguë au stress réplicatif dans le contexte BRCA1-Def qui induit l'arrêt des fourches de réplication. Cela pourrait conduire à un effondrement de la fourche de réplication et éventuellement à des ruptures massives d'ADN double brin (DSB). Pour tester cette hypothèse, nous avons réalisé des expériences d'électrophorèse en champ pulsé qui ont clairement montré une accumulation importante de DSB dans les cellules BRCA1-Def 48h après le lavage de gemcitabine. Ces DSB ne résultaient pas du clivage apoptotique de l'ADN car le traitement conjoint avec la gemcitabine et l'inhibiteur de l'apoptose Z-VAD FMK n'a pas modifié le niveau de DSB, suggérant que les DSB résultaient d'une accumulation d'ADNsb non protégé. Ensuite, nous avons testé si l'accumulation d'ADNsb résultait d'une surrésection causée par une activité incontrôlée de l'exonucléase MRE11 dans la cellule BRCA-Def et avons appliqué un traitement conjoint de gemcitabine et Mirin. En fait, l'inhibition de MRE11 avec Mirin a entraîné une diminution spécifique du nombre de cellules présentant la coloration ɣH2AX pannucléaire. Enfin, nous avons noté que les cellules BRCA1-Def étaient sujettes à des glissements mitotiques conduisant à des catastrophes mitotiques illustrées par une accumulation importante de mitoses aberrantes et de micronoyaux dans ces lignées. De manière notable, les micro-noyaux ont montré une double coloration positive BrdU et ɣH2AX pannucléaire indiquant qu'ils correspondaient à la fragmentation des noyaux avec un niveau important d’ADNsb. Nous avons également pu montrer que l'hypersensibilité des cancers BRCA1-Def au stress réplicatif aigu est reproductible in vivo dans des modèles PDX, dont les coupes de tissus montraient un profil de marquage ɣH2AX pannucléaire, en corrélation avec leur statut de réponse à la gemcitabine
About 15% of triple negative breast cancers (TNBC) are BRCA defective and show Homologous Recombination DNA repair Deficiency (HRD) and increased sensitivity to genotoxic drugs. We hypothesized that BRCA-defective TNBC are highly sensitive to replicative stress inducing drugs, which could open therapeutic perspectives. Our results show that BRCA1-deficient (BRCA1-Def) TNBC, as well as BRCA1-Def ovarian cancer cell lines showed increased sensitivity to Gemcitabine. Noticeably, Gemcitabine induced increased cell death in BRCA1-Def cells, associated with mediocre replicative stress management. Indeed, up to 80% of BRCA1-Def cells displayed persistent gH2AX staining even 48h after washing off Gemcitabine, compared with their BRCA1-WT counterpart in which staining had decreased significantly. Furthermore, Gemcitabine treated BRCA1-Def cells showed a persistent imbalance between RPA32-positive and gH2Ax-positive cells, suggesting unresolved replication stress in these cells and occurrence of replication catastrophe in a substantial fraction of the cells. Furthermore, an important fraction of gH2AX+ cells displayed pan-nuclear staining, which numbers steadily increased over time in Gemcitabine treated BRCA1-Def cells, while they decreased in the BRCA1-WT counterpart. Interestingly, nearly 90% of gH2AX pan-nuclear cells were completely negative for RPA32 and showed a strong BrdU staining in non-denaturing conditions, indicating an important accumulation of single stranded DNA specifically in these cells. Noticeably, an important number of cells with pan-nuclear gH2Ax staining were also negative for RAD51 foci, but were positive for both 53BP1 and FANCD2 foci. The opposite landscape was observed in the BRCA1-WT cells in which gH2AX pan nuclear cells were RAD51+ and 53BP1- and FANCD2-. These results indicate an acute replicative stress response in the BRCA1-Def context that induces replication forks arrest. This could lead to replication fork collapse and possibly massive DNA Double Strand Breaks (DSB). To test this hypothesis, we performed Pulse Field Gel Electrophoresis experiments that clearly showed important accumulation of DSBs in the BRCA1-Def cells 48h after Gemcitabine release. These DSBs did not result from the apoptotic cleavage of DNA as joint treatment with Gemcitabine and the apoptosis inhibitor Z-VAD FMK did not modify the DSB level, suggesting that DSBs resulted from an accumulation of unprotected ssDNA. Next we tested whether the accumulation of ssDNA resulted from over-resection caused by uncontrolled activity of the exonuclease MRE11 in BRCA-Def cell and applied a joint treatment of Gemcitabine and Mirin. As a matter of fact, inhibition of MRE11 with Mirin resulted in a specific decrease of the number of cells presenting the pan-nuclear gH2AX staining. Finally, we noted that BRCA1-Def cells were prone to mitotic slippage leading to mitotic catastrophes illustrated by an important accumulation of micronuclei in these cells. Noticeably, micro-nuclei showed double positive BrdU and pan nuclear gH2AX staining indicating that they corresponded to fragmentation of nuclei with elevated ssDNA content. We have also been able to show that the hypersensitivity of BRCA1-Def cancers to acute replication stress is reproducible in vivo in PDX models, which displayed a pan-nuclear gH2AX staining profiles, in accordance with their Gemcitabine response status. Hence, we propose that pan-nuclear gH2Ax staining could be a marker of replication catastrophe in treated tumors and could possibly be considered as a biomarker of the response to replicative stress. Hence, in a BRCA-Def context Gemcitabine treatment has combined lethal consequences, massive replicative and mitotic catastrophe

Loss of function mutations in the farnesyltransferase β subunit gene ERA1 (enhanced response to abscisic acid), cause abscisic acid hypersensitivity in seedlings and in guard cells. This results in slowed water loss of plants in response to drought. Farnesyltransferase (PFT) catalyses the attachment of the 15-carbon isoprenoid farnesyl to conserved cysteine residues located in a conserved C-terminal domain designated CaaX box. PFT is a heterodimeric protein comprised of an a and b sununits. The a subunit is shared between PFT and geranylgeranyltransferase-I (PGGTI) which catalyses the attachemt of the 20-carbon isoprenoid geranylgeranyl to CaaX box proteins in which the last amino acid is almost always leucine and in addition have a polybasic domain proximal to the CaaL box. Preliminary data presented in the proposal showed that increased cytoplasmic Ca2+ concentration in stomal guard cells in response to non-inductive ABA treatements. The goals set in the proposal were to characterize better how PFT (ERA1) affects ABA induced Ca2+ concentrations in guard cells and to identify putative CaaX box proteins which function as negative regulators of ABA signaling and which function is compromised in era1 mutant plants. To achieve these goals we proposed to use camelion Ca2+ sensor protein, high throughput genomic to identify the guard cell transcriptome and test prenylation of candidate proteins. We also proposed to focus our efforts of RAC small GTPases which are prenylated proteins which function in signaling. Our results show that farnesyltransferaseprenylates protein/s that act between the points of ABA perception and the activation of plasma membrane calcium influx channels. A RAC protein designated AtRAC8/AtRop10 also acts in negative regulation of ABA signaling. However, we discovered that this protein is palmitoylated and not prenylated although it contains a C-terminal CXXX motif. We further discovered a unique C-terminal sequence motif required for membrane targeting of palmitoylatedRACs and showed that their function is prenylation independent. A GC/MS based method for expression in plants, purification and analysis of prenyl group was developed. This method would allow highly reliable identification of prenylated protein. Mutants in the shared α subunit of PFT and PGGT-I was identified and characterized and was shown to be ABA hypersensitive but less than era1. This suggested that PFT and PGGT-I have opposing functions in ABA signaling. Our results enhanced the understanding of the role of protein prenylation in ABA signaling and drought resistance in plants with the implications of developing drought resistant plants. The results of our studies were published 4 papers which acknowledge support from BARD.