Monthly Archives: May 2018

Tissue factor pathway inhibitor TFPI

Tissue factor pathway inhibitor-2 (TFPI-2) is also known as matrix-associated serine protease inhibitor (MSPI) and placental protein 5 (PP5) (Rao et al., 1995; Kisiel et al., 1994). TFPI-2 is a kunitz-type serine proteinase inhibitor, which is abundantly expressed in a variety of human tissues such as liver, pancreas, skeletal and directionally secreted into the extracellular matrix (ECM) (Miyagi et al., 1994; Sugiyama et al., 2002; Herman et al., 2001). TFPI-2 is thought to negatively regulate the enzymatic activity including matrix metalloproteinase (MMP), plasmin, cathepsin G, trypsin, and plasma kallikrein (Stamenkovic, 2003; Kempaiah et al., 2007). Previous studies have suggested that the expression of TFPI-2 is down-regulated in many malignant tumors, including breast cancer, gastric stromal tumor, cervical cancer, gliomas and non-small-cell lung cancer, and low expression of TFPI-2 was associated with poor prognosis in cancer patients (Wang et al., 2014; Zhang et al., 2013; Rao et al., 2001; Rollin et al., 2005; Xu et al., 2013).
The therapy of induced differentiation of tumors is proposed in recent years, which indicates a new direction for the treatment of hepatocellular carcinoma. Commonly used differentiation-inducing agents are mostly substances that might work on other malignancies. But generally speaking, the therapy of induced differentiation of hepatocellular carcinoma has not yet yielded satisfactory results. It has been reported that transmembrane protease, serine 4 (TMPRSS4) is upregulated by the silencing of TFPI-2 through aberrant DNA methylation in non-small-cell lung cancer (Hamamoto et al., 2015). TMPRSS4 has been shown to be an important regulator during the epithelial-mesenchymal transition (EMT) in human epithelial cancer smoothened (Li et al., 2011). EMT is a physiological mechanism which is present during development, including mesoderm formation and neural tube formation (Kalluri and Weinberg, 2009). Previous studies showed that the EMT process may facilitate the generation of cancer cells with the mesenchymal traits needed for dissemination as well as the self-renewal properties needed for initiating secondary tumors (Hollier et al., 2009). Our previous studies indicated that TFPI-2 could not only inhibit the proliferation, invasion and metastasis of Hep3B and HepG2, but also significantly reduce the expression and secretion of alpha-fetal protein (AFP), a maker of HCC (Xu et al., 2011). Therefore, we hypothesize that TFPI-2 may show an effect on inducing the differentiation of hepatocellular carcinoma cells (HCC) into mature hepatocytes and serve as a novel way for the treatment of hepatocellular carcinoma.

Materials and methods


TFPI-2, also known as placental protein (PP5), is identified as a tumor suppressor gene (Bretz et al., 2012). As a member of the Kunitz structure superfamily, TFPI-2 is a broad-spectrum inhibitor of serine protease. Since the promoter of TFPI-2 is rich in CPG islands, its expression is silenced in many malignant tumors through epigenetic modifications, including promoter methylation and histone deacetylation (Dong et al., 2015; Glockner et al., 2009). In addition, the aberrant splicing form of TFPI-2 was detected during cancer progression, which represented an untranslated form providing another mechanism (Bretz et al., 2012). Moreover, TFPI-2 could mediate dephosphorylation of residues outside the T-loop of ERK, which may directly impact kinase function (Mazalouskas et al., 2014). The ERK1/2 pathway integrates various cytosolic signals to regulate cellular proliferation, differentiation, and apoptosis, which contributes to the formation and development of a variety of tumors (Deng et al., 2013; George et al., 2007).
Tumors are organized in a hierarchy of heterogeneous cell populations with different biologic properties comprising proliferating transit-amplifying cells, terminally differentiated cells, and dying cells and that the populations consist of cancer stem cells (CSCs). Some of the proliferating cells do not differentiate into mature cells, which could continue to proliferate. The CSCs are thought to maintain tumor cells self-renewal capacity, high proliferation rate and are more resistant to chemotherapy than differentiated cancer cells (Ciurea et al., 2014; Puglisi et al., 2013). Differentiation therapy could force hepatocellular carcinoma cells to differentiate and lose self-renewal capacity. Cell differentiation is assumed to be regulated by an informational network, including transacting factors, soluble transmitters and cell-matrix adhesion molecules. But, to our knowledge, little is known on the role of TFPI-2 inducing differentiation in hepatocellular carcinoma.

A generation is defined by Oxford dictionaries online

A generation is defined by Oxford dictionaries online as all of the people born and living at about the same time, regarded collectively. Generation Y describes the generation born in the 1980s and 1990s, typically perceived as increasingly familiar with digital and electronic technology. The term “Generation Y” was the term given to the generation following Generation X. Millenials, Y Generation, Generation We, Echo boomers and many more terms have been used to describe this generation. Although the term Generation Y is used worldwide, there is no consensus over the exact birth dates that constitute this generation, therefore, resulting in much debate globally. The US, Canada, Australia and the UK utilize somewhat different years when statistically analyzing this generation. If we use the same concept in Saudi Arabia, we may presume that Generation Y includes the young generation of dentists who will be part of the future practitioners, educators, administrators and leaders in the dental community. This is particularly significant as currently there are several government and private dental colleges in Saudi Arabia which will increase the number of Generation Y graduates. The United Nations, World Population Prospects: 2008 revision reported that in Saudi Arabia the median age in 2009 was 24.3years and is expected to be 36.6 in 2050. The 2010 Population Reference Bureau reported that in Saudi Arabia, youth constituted 27% of the working-age population in 2010. The expected percent change in the number of youth between 2010 and 2040 is 22%, which is expected to be negative in other countries.

Stress has now become an ingrained part of our vocabulary and daily existence. Originating a little more than 50years ago the term is now in popular parlance. Stress, as coined by Hans Selye in the early 1930s, is a biopsychosocial model that refers to the consequence of failure of an BV6 to respond adequately to mental, emotional or physical demands, whether actual or imagined (Selye, 1982). The dental training curriculum demands that students master multiple domains of not only theory but also clinical proficiencies and patient-relation protocols (Rajab, 2001), resulting in a strenuous lifestyle affecting one’s physical and mental well-being. A recent report from the British Association for Counseling and Psychotherapy states that stress-induced emotional imbalance has been on the rise during the past few decades among the student population. The number requiring intervention by therapists has also increased considerably. However, the prime focus remains on what determines the ability of a few students to cope with stressors while others succumb to stress in the dental learning environment.
According to Selye (1982), the proper evaluation of dental environmental stress includes three essential components. External components are the dental environmental stressors. Internal components are the physiological and biochemical factors in one’s internal environment (body), the perceived stress. The cognitive responses resulting from the interaction between these two components are the coping strategies that constitute the third component. Scientific evidence shows the multifactorial nature of stress among students, thus making its assessment difficult. Apart from excellence in academic performance, the precise technical requirements of dentistry make the transition from preclinical to clinical all the more stressful (Pau and Croucher, 2003; Radcliffe and Lester, 2003).
Goldstein (1979) initiated a stress study in dental schools following which there was development and refinement of several questionnaires by Garbee et al. (1980). The best of all accounts, in terms of consistency, was the one framed by Grandy et al. (1984a) in the dental environmental stress (DES) questionnaire that includes a clear distinction of eustress from distress. Perceived stress is the appraisal of potentially threatening life events by an individual, being influenced by his or her attitudes and beliefs (Tedesco, 1986). Perfectionism, fueled by past academic achievements and future scholastic expectations, is reported as a major cause of perceived stress in preclinical students (Atkinson et al., 1991). Stress can be physiological only if it stays within a certain limit beyond which it advances to the stage of distress.

br Discussion The clinical success of

The clinical success of pit and fissure sealants is directly linked to their capacity to remain bonded to occlusal pits and fissures (Papacchini et al., 2006). The polymerized material forms a strong micromechanical bond to etched tooth enamel, thus physically protecting susceptible areas of the tooth surface and preventing dental caries (Christopher et al., 2009). Polymerization is a complex chemical mechanism in which two or more molecules combine to form a larger polymer molecule that consists of a repeating structural unit. Previous studies have reported DC values ranging from 45% to 85% in bis-GMA-based resin composites due to the complex mechanism of polymerization (Emami and Söderholm, 2005; Price et al., 2005; Soares et al., 2007). To date, the shortest curing time required to achieve a clinically satisfactory DC has not been specifically established, but the results of the present study indicate that a curing time of 40s provided a satisfactory DC when compared to 60s. However, a satisfactory DC was not achieved with a curing time of 20s, which was recommended by the manufacturer.
The neurokinin receptor antagonist
in the present study that extended light exposure would increase the DC was partially accepted. Manufacturers recommended curing for 20s, but curing for 40s provided a higher DC than 20s. Researchers have reported that an extended curing time using light sources generates more heat and leads to a higher DC in composite resin (Bagis et al., 2008; Trujillo et al., 2004). However, we observed no increase in DC upon curing for 60s. A possible explanation for this result is that the light transmission may have decreased with time (Shortall et al., 2008). The filled flowable resin (Filtek™ Z350 XT) showed a higher DC than the unfilled pit and fissure sealant (Clinpro™). This result may be due to differences in the filler content of the two materials, or it may be due to differences in their organic content. Clinpro™ contains more bis-GMA monomers and had a lower DC than flowable Filtek™ Z350, which contains a lower organic content. The results are also influenced by several factors, such as monomer composition, material translucency, and the concentration of photo initiator (Calheiros et al., 2004). It is well known that there is a direct relationship between the DC of dental composites and curing light intensity (Rueggeberg et al., 1993).
The results of the present study are similar to those of Boniek et al. (2010) who demonstrated that a pit and fissure sealant showed a lower DC than a flowable composite. An extended curing time would prolong the excitation of photo initiator molecules, and filled flowable resin (Filtek™ Z350 XT) might contain more photo initiator molecules then the unfilled pit and fissure sealant (Clinpro™). This explanation could account for the higher DC in flowable Filtek™ Z350 than in the unfilled pit and fissure sealant. The results of the present study were in accordance with those of previous studies (Aguilar et al., 2007; Musanje et al., 2009; Silva et al., 2008). Moreover, a previous study demonstrated that an increased amount of triethylene glycol dimethacrylate (TEGDMA) in an experimental dimethacrylate-based polymer matrix led to an increased conversion of the monomer (Goncalves et al., 2008). Similarly, in the present study, the flowable composite showed a higher DC due to the increased TEGDMA content.

Within the limitations of this study, the following conclusions were obtained:

Ethical statement

Conflict of interest

As a prerequisite to orthodontic treatment, patient functional and aesthetic needs are taken into consideration. Several indices have been developed over the years to quantify these needs (Borzabadi-Farahani, 2011); however, each method has its limitations. The Handicapping Labio-lingual Deviation Index (HLD) (Draker, 1960) is unable to record missing and impacted teeth, or spacing and transverse discrepancies. The Dental Aesthetic Index (DAI) (Cons et al., 1986) reflects malocclusion severity as per the North American culture, aesthetic and psychosocial value, but does not assess occlusal anomalies such as buccal cross-bite, impacted teeth, deep overbite, mesio-distal discrepancy, and severity of arch length discrepancy. The Index of Complexity, Outcome and Need (ICON) (Daniel and Richmond, 2000) is highly weighted towards aesthetics; hence, it is more subjective than objective in its assessment.

Introduction Workflow interruptions are common stressors in health

Workflow interruptions are common stressors in health care [1]. The consequences of workflow interruptions are not bad per se[2]. Sometimes the need to switch from one task to another more “critical” task is positive even when the first task is delayed [3]. Although such workflow interruptions are sometimes helpful in surgery (e.g., a note about adhering to the principles of asepsis), a majority of interruptions (e.g., nonpatient-related private conversation) are not [4]. Workflow interruptions interfere with the pursuit of tasks and can cause errors in carrying out actions, even in routine tasks that have been finished without error many times previously [5,6]. Thus, workflow interruptions are an avoidable threat to surgery outcomes and patient safety.
In their recent review of 33 studies, Rivera-Rodriguez and Karsh [4] reported only seven studies of interruptions and cognitive function in health care and concluded that more studies should focus on cognitive function because “these cognitive implications of interruptions are at the methysergide of why the study of interruptions is important” (p. 309). The current study on workflow interruptions tests cognitive failure in the action regulation of routine tasks as the critical link between interruptions and near-accidents.
Workflow interruptions may trigger failure in action regulation [7]. When there is an interruption, attention must be diverted to the interruption agent and away from the current task at hand. The goal of the interrupted action and its position in the action sequence must be stored in working memory. Moreover, the additional goal of restarting the interrupted task at hand at a later time must be stored in prospective memory [7]. The negative consequences of interruptions arise from these growing costs of action regulation while performing routine tasks. A typical error that is caused by workflow interruptions is the error of omission: for example, a theater nurse is interrupted by a nonpatient-related question and forgets to fill out the form while preparing a device because the restart of the action sequence is misplaced (a place-losing error, p. 29) [7]. Wallace and Chen [8] suggested adverse work conditions, including workflow interruptions, make cognitive failure during routine tasks more likely.
It is not only interruptions at work that can cause concern about cognitive failure and near-accidents, but also individual differences in conscientiousness and safety compliance. Indeed, the first conceptualizations considered cognitive failures primarily as randomly appearing or based on individual trait-like cognitive failure proneness [9,10]. Wallace and Chen [8] showed that work-related cognitive failure not only corresponds to work demands, but is also negatively related to individual conscientiousness. Wallace and Chen [8] supposed that conscientiousness was negatively related to workplace cognitive failure, presumably because “individuals higher on conscientiousness should be more attentive to work tasks and thereby not commit as many cognitive failures” (p. 618). In phytochrome study, we controlled for individual differences in conscientiousness and safety compliance by including both in the prediction model. We assumed an indirect path from workflow interruptions through failure in action regulation to near-accidents during surgery beyond personal conscientiousness and safety compliance. Therefore, for this study on workflow interruptions in surgery we hypothesized that workflow interruptions are positively associated with failure in action regulation (H1) and near-accidents (H2). Moreover, we expected a significant indirect path from workflow interruptions through failure in action regulation to near-accidents in surgery (H3).

Materials and methods

Table 1 shows the mean values and SDs of the study variables. One or more near-accidents during surgery in the past 4 weeks were reported by more than half of the nurses (mean = 1.19, SD = 2.00). The mean level of total workflow interruptions was 2.13 on the five-point scale (SD = 0.50). Interruptions by persons including patients were also moderate (mean = 2.24, SD = 0.58). Interruptions by malfunction (mean = 2.25, SD = 0.64) and interruptions by blockages (mean = 1.90, SD = 0.61) were also moderate. The mean level of failure in action regulation was low (mean = 1.87, SD = 0.45), whereas the mean levels of safety compliance (mean = 4.01, SD = 0.82) and conscientiousness in the study sample were high (mean = 5.01, SD = 0.68).

thrombopoietin receptor agonist Applying the microstructure core makes it possible to gain

Applying the microstructure core makes it possible to gain higher relative sensitivity and alleviates confinement loss. Besides, it can be analyzed that enhancing the diameter of the air holes in the core region and decreasing the pitch Λc, the relative sensitivity is promoted [5]. Fig. 9 shows the effect of air filling ratio dc/Λc in core region kept fixed other parameters. At the wavelength 1.33μm, the variation of dc/Λc defined as 0.95, 0.93 and 0.92 the considered relative sensitivities are 55.84%, 55.10% and 51.07% respectively. It can be also mentioned that the evanescent field can be absorbed into core by promoting dc/Λc which leads to enhance the thrombopoietin receptor agonist power causes sensitivity increases. On the other hand, the capability of core to absorb the power fraction is low when the air filling ration dc/Λc decreases as well as sensing capability will fall. Fig. 10 represents the effective area and nonlinearity of the proposed S-PCF for the optimum parameters.
After completing of simulation process investigating the effects of distinguish parameters on proposed S-PCF, it is evidently reported that the relative sensitivity can be promoted due to the global diameter decrement shown in Table 1. High sensitivity leads more confine of light into core region as well as better electromagnetic power interaction with gases. The above table also exhibits the effect of changing global parameters of ±1% and ±2%, on birefringence, effective area and nonlinearity. From above investigation, it is nicely visualized that the effective refractive index of the fast-axis direction is lower than that of the slow-axis direction and the difference exhibits a high birefringence. It is noticed that effective area promotes according to the increase thrombopoietin receptor agonist of diameter of air holes as well as decreases the non-linear coefficient. The mode power narrowly demarked in the core region at longer wavelength, so the guiding waves diverse largely. As a result, the propagating modes hold larger effective area [48].
Table 2 demonstrates the comparison between relative sensitivity, birefringence. Effective area and nonlinearity of the proposed S-PCF with other prior designs and the proposed S-PCF provides 55.10% sensitivity and birefringence order of 7.23×10 at a wavelength of 1.33μm. In some prior structures, birefringence, effective area and nonlinear coefficient properties were not analyzed. From above comparisons, ossification can be clearly reported that the proposed S-PCF will be more effectible for sensing applications such as toxic and colorless gases.
Finally, the fabrication process is one of the fundamental issues in PCFs. In the proposed S-PCF four types of different air-hole are considered and shown in Fig. 1. Different methods have been offered for the fabrication of micro-structured fibers such as stack and draw [49], drilling [50], sol-gel casting [51], and extrusion [52] methods. Triangular or honeycomb lattices can be fabricated by Stack and draw methods but cannot easily generate circular patterns. The drilling methods offer adjustment of both holes size and spacing but are usually limited to a few number of holes and bounded to circular shapes. Extrusion techniques permit design freedom, but are typically restricted to soft glasses causes the material loss values are severely high. Hamzaoui et al. [51] proposed sol-gel technique to fabricate the PCFs structures and they provide the freedom to adjust air-hole size, shape, and spacing. So, the proposed S-PCF can be successfully fabricated by utilizing the sol-gel casting method.

A spiral shape photonic crystal fiber (S-PCF) has been proposed and analyzed that contains two layers porous core with circular air holes. The reported S-PCF exhibits highly relative sensitivity and ultra-high birefringence consequently between the wider wavelength ranges from 1μm to 1.8μm. From all investigated results of the proposed S-PCF show that the relative sensitivity and birefringence of 55.10% and 7.23×10 accordingly at the operating wavelength of 1.33μm. In addition, the effective area and nonlinearity of 11.60μm2 and 12.62Wkm respectively are achieved at the same wavelength. So, our proposed S-PCF ensures revolutionary change in toxic and colorless gas detection as well as environment pollution monitoring.

In Fig the relative sensitivity curve

In Fig. 4, the relative sensitivity curve with different core formation of the proposed S-PCF has been analyzed. To investigate the core region, it is fixed the cladding and taken different core formation to ensure the effectiveness of the PCF [32]. It has been selected circular holes of two layers instead of one and three layers in the core region and set it as core to investigate the optimum results. From all the evaluation results, it can be described that the arrangements of air holes in the proposed S-PCF show higher sensitivity compare to other organizations of holes in the core region. It also demonstrates that the fiber will be effective as a single mode around the entire bands. The considered relative sensitivities are 43.16%, 55.10% and 52.98% when the core is formatted into one layer, two layers and three layers air holes respectively at wavelength of 1.33μm.
Fig. 5 shows the diameter variations of cladding d1 keeping fixed other parameters (Λ=2.18μm; Λc=0.60μm; dc=0.56μm; d2=1.56μm and d3=2.04μm). At the operating wavelength 1.33μm, the variation of d1 as 1.22, 1.26 and 1.30μm the air filling ration in cladding is defined as d1/Λ=0.56, 0.58 and 0.60 the considered relative sensitivities are 49.96%, 55.10% and 57.16% respectively. By the reduction of air filling ratio d1/Λ, the evanescent field is penetrated into cladding causes the fraction power of holes alleviates and leads to decrease the telomerase inhibitors power by core region which results relative sensitivity decreases. On the other hand, if it is increased the air filling ratio d1/Λ, the evanescent field is penetrated into core region causes the fraction power of holes enhances which leads to increase the absorption power by core region that results relative sensitivity increases. The higher sensitivity makes a fiber as an active candidate to detect noxious gas, colorless gas and environment pollution monitoring [47]. Now d1/Λ=0.58 is selected for optimizing investigation process.
In Fig. 6, the relative sensitivity versus wavelength curve for variations of air filling d2/Λ in the cladding region is illustrated by keeping fixed other parameters. According to the variation of d2/Λ as 0.70, 0.72 and 0.74 the calculated relative sensitivities (Fig. 6) are 53.98%, 55.10% and 55.26% respectively at the operating wavelength 1.33μm. From this figure, it is noticed that by enhancing the air filling ratio d2/Λ, the power fraction can be absorbed strongly into core region causes relative sensitivity will promote which will be beneficial for sensing applications [11]. In the reverse order, the relative sensitivity decreases when air filling ratio (d2/Λ) decreases.
Fig. 7 exhibits the influence of air filling ration (d3/Λ) on relative for the proposed S-PCF. According to the figure, it is noted that if air filling ratio d3/Λ increases, the evanescent field is strongly confined into circular core region causes power fraction of air holes enhances which leads to increase the absorption power that results relative sensitivity dramatically increases. With the variation of d3/Λ as 0.92, 0.93 and 0.95, the achieved relative sensitivities are 53.96%, 55.10% and 55.50% respectively at wavelength 1.33μm. By comparing Fig. 5, Fig. 6 and Fig. 7, it can be mentioned that the diameter (d1) of first layer is more sensitive for sensitivity than d2, d3.
Now to acquire the expected result the pitch is chosen as Λ=2.18μm for optimizing investigation process. From Fig. 8(a), it is clearly visualized that the variation of pitch (Λ) has great effect on relative sensitivity to increase or decrease sensitivity that makes the fiber more practical in the sensing applications like toxic and colorless gas detection. The relative sensitivity versus wavelength curve for variations of pitch (Λ) of cladding is depicted in Fig. 8(a) when the other parameters (Λc=0.60μm; dc=0.56μm; d1=1.26μm d2=1.56μm and d3=2.04μm) are kept constant. According to the variation of Λ as 2.15, 2.18 and 2.21μm, the calculated relative sensitivities are 58.70%, 55.10% and 49.64% respectively. From above observation, it can be mentioned that the higher relative sensitivity can be gained by reducing pitch of cladding Λ as much as possible. In another sense, it can be expressed that if it is enhanced Λ, the evanescent field would not properly be confined into core a cause the power fraction of holes alleviates which governs to decrease the absorption power by core region as well as relative sensitivity decays. From Fig. 8(b), it is visualized that after variation of pitch the fiber remains constant to single mode over the band of interest.

The MCF cells were treated with

The MCF-7 mdm2 p53 were treated with either doxorubicin or OA extract alone or in combination for 12 and 24h respectively and intracellular ROS generation was quantitatively measured by HDCF-DA assay using spectrofluorometry. The results mdm2 p53 (Fig. 3) revealed that OA extract alone was insignificant in generation of ROS while doxorubicin treatment significantly increased the level of ROS up to 1.34 and 1.78-fold in 12 and 24h duration respectively. On the contrary, the simultaneous treatment reduced significantly (p<0.05) the level of ROS at 100 and 150μg/ml. The lowest concentration of OA extract (50μg/ml) was found not to be effective. However, the exposure of OA extract significantly prevented the ROS induced by doxorubicin in MCF-7 cells. The potential of OA extract on doxorubicin induced lipid peroxidation in MCF-7 cells is summarized in Fig. 4. As shown in figure, exposure of 50μM doxorubicin resulted in a significant (p<0.05) increase in membrane lipid peroxidation of 1.33 and 1.66-fold at 12 and 24h respectively, as compared to the control cells. While, OA extract alone did not induce lipid peroxidation. Whereas, co-exposure of OA extract significantly reduced the lipid peroxidation specifically at higher duration and concentration. The effect of OA extract on the depletion of glutathione induced by doxorubicin exposure is presented in Fig. 5. The results clearly indicated that treatment with doxorubicin at 50μM reduced the glutathione level up to 28% and 49% after 12 and 24h, respectively in MCF-7 cells. While OA extract found to be ineffective in changing the level of glutathione in these cells. Eventually, the co-exposure of OA extract resulted in the significant recovery of glutathione level. The level of glutathione reached up to 96% and 88% at 100 and 150, 50μg/ml concentration. The exposure of OA extract alone did not induce any changes in the activity of SOD in MCF-7 cells. While treatment with 50μM doxorubicin significantly reduced the activity of SOD after 12 and 24h, which were determined as 65% and 43% respectively, when compared with the control (Fig. 6). On the other hand, exposure of OA extract significantly attenuated the SOD activity that was found to increase up to 85% and 78% after 12 and 24h, respectively. Doxorubicin is an anthracycline and potent antitumor drug widely used in the clinic for the treatment of a broad spectrum of cancers (Buzdar et al., 1985; Singal and Iliskovic, 1998). However, this drug continues to pose serious concern such as generation of ROS resulting in oxidative stress and cellular changes. Overproduction of ROS can cause oxidative damage to biomolecules (lipids, proteins, DNA) (Uttara et al., 2009). In the present study, doxorubicin increased significantly ROS level which leads to the changes in oxidative stress biomarkers in MCF-7 cells. However, the simultaneous treatment of MCF-7 cells with different concentrations of OA extract decreased the ROS generation and MDA level which is a biomarker of lipid peroxidation. Moreover, the levels of the antioxidant molecule, glutathione, and the activity of the antioxidant enzymes, superoxide dismutase, were elevated as compared to doxorubicin treatment alone. These findings confirmed the antioxidant potential of OA extract in MCF-7 cells that could be attributed to the presence of major flavonoids such as kaempferol, quercetin, isorhamnetin and luteolin (Barakat et al., 1991; Cristea et al., 2003; Moiteiro et al., 2008; Marques et al., 2009; Berrehal et al., 2010; Villela et al., 2011). The majority of natural antioxidants are polyphenols including flavonoids, which exhibit strong antioxidant activity by acting as free radical scavengers, hydrogen donors, singlet oxygen quenchers, and metal ion chelators, in addition to inducing gene expressions of antioxidant enzymes (Krinsky, 1992; Rice-Evans, 2001).
The OA extract was diluted and filtered through a 0.22μm PVDF syringe filter (Membrane Solutions, Texas, USA) before being injected into the UPLC–MS system. The spectrum obtained by direct infusion (both in ESI +Ve and –Ve mode) of OA extract is shown in Fig. 7. The major peaks in the –Ve mode were observed at m/z ratio of 97.26, 115.49, 570.61 and 572.56 while in the +Ve mode a peak at m/z ratio of 104.52 was evident. Identification of the compounds could be done with the aid of (m/z) ratio evaluation of the resulting data by searching against the spectral library.

Algunos de nuestros documentos sugieren la existencia de claras

Algunos de nuestros documentos sugieren la existencia de claras distinciones entre las deidades y sus representaciones. Según Durán (1995: II 171) el objeto último del culto Atractyloside Dipotassium Salt manufacturer las efigies de cerros no eran los montes en sí, “ni tampoco hemos de entender que los tenían por dioses ni los adoraban como á tales que su intento á mas se estendía que era pedir desde aquel cerro alto al Todopoderoso”. En torno a los mayas peninsulares, Landa (1938: 123) explicó que “bien sabían ellos que los ídolos eran obras suyas y muertas y sin deidad, mas los tenían en reverencia por lo que representaban y porque los habían hecho con muchas ceremonias”. Los tlaxcaltecas, por su parte, declararon “estos bultos y estatuas a quien servimos y adoramos son imágenes, figuras y simulacros de los dioses que en la tierra fueron hombres, y por sus hechos heroicos y famosos subieron al cielo” (Muñoz Camargo, 1998: 197). cuenta que las deidades petrificadas de Tojil, Awilix y Jaqawitz solían devorar a los enemigos de los quichés; pero, líneas más tarde, se explica que “solamente era el nawal de las piedras” quien lo hacía.
En otros casos, por el contrario, no solo se indica que tales objetos fungían como medio de comunicación con las deidades y estaban facultados para escuchar y responder (véanse Pérez de Rivas, 1944: 491-493; Pomar, 1941: 14; Garza et al., 1983, II 187, 322), sino que además suponían tener vida y ser capaces de actuar por su propia voluntad: Las Relaciones de Xalapa, Cintla y Acatlan (en Acuña, 1984: 288) explican que, para los antiguos totonacas, las efigies de piedras y palos “tenían su juicio y razón”. Asimismo, los nahuas de Coatepec decían que “antes q[ue] los españoles viniesen, el Demonio que se revestía en este ídolo de piedra [en el que se transformó Quetzalcóatl], daba muy grandes voces y aullidos de día y de noche” (Relación de Coatepec en Acuña, 1985: I 136).
Es claro que, a pesar de ser ixiptla de los dioses, no todos los gobernantes eran vistos como deidades. Pues, aun cuando los documentos puedan atribuirles cualidades sobrenaturales (véase Martínez González, 2011: 275-284; 2013: 171-212), el propio Motecuhzoma supone haber explicado a desmosome Cortés que sabía que había oído decir “que yo era y me hacía Dios […] A mí veisme aquí que so[y] de carne y hueso como vos y como cada uno, y que soy mortal y palpable” (Cortés, 1963: 59). La situación es todavía más claramente tratada en el Códice Florentino (Sahagún, 1950-1982: VI 52), cuando refiere el discurso que se dirigía al recién elegido gobernante: “Te has vuelto dios, aunque seas humano como nosotros, aunque seas nuestro hijo, nuestro hermano menor, nuestro hermano mayor, ya no eres humano como nosotros, no te vemos como humano. Tú ya representas [ca ie titeuiuiti], remplazas a alguien [ca titepatilloti]”. Así, Graulich (1998: 103) concluye que “[el gobernante] no es divino pero representa al dios. Es la deidad quien designa al rey y éste es como su imagen, su lugarteniente, su sustituto o su cobertura”. Lo interesante es que, pese a que los mandatarios no Atractyloside Dipotassium Salt manufacturer son dioses, en cada uno de ellos se encuentra el potencial para devenirlo. Los casos más emblemáticos son sin duda los de Quetzalcóatl —señor de Tula— y Huitzilopochtli —caudillo de los mexicas en su peregrinación— que, después de la muerte, se transformaron en las principales deidades de sus pueblos (Castillo, 2001: 121-122; Códice Chimalpopoca: Anales de Cuauhtitlan y Leyenda de los soles, 1945: 11). Pero también conocemos a gobernantes más mundanos que terminaron siendo divinizados; tal es el caso de Tlacatecatzin de Tezcoco (Torquemada, 1975-1979: II 125), Hiquingaje de Michoacán (Alcalá, 2008: fol. 137), Petela de Oaxaca (“Relación de Chichicapa”, en Acuña, 1984: I 90) y Gran Nayar entre los coras del siglo xviii (Tavárez Bermúdez, 2012: 431; Malvido, 2000). Incluso, algunos documentos señalan que los muertos más distinguidos y, en especial, los señores devenían dioses tras su deceso (Durán, 1995: I 454; Sahagún, 1950-1982: X 192; Torquemada, 1975-1979: IV 125-126; Códice Vaticano A, 1964-1967: lam. 5).

Among the other studied variables i e implant length

Among the other studied variables (i.e. implant length, diameter and subtype; age and gender of patients; upper/lower jaw, site and post-extractive/healed bone; type of prosthesis, N.P.U., type of edentulism, and type of antagonist element), post-extractive implants and N.P.U. were statistically significant in univariate analysis (Table 1) whereas in multivariate analysis, only post-extractive implants have a significant adverse effect on crestal bone resorption (Table 2). This result can be due to the short follow-up (i.e. about 1year) where post-surgical crestal bone remodeling effect is higher.
In conclusion, adjacent implants inserted with a distance lower and higher than 1.8mm have difference in crestal bone resorption but this difference is not statistically significant in a short period follow up. This could due to the specific implant used that has a reverse conical neck. No statistical difference was detected between implant subtypes. Post-extractive implant insertion is the major determinant in terms of peri-implant bone resorption in a short period follow-up.


Oral hygiene maintenance is of supreme importance in patients undergoing fixed orthodontic treatment. Tooth brushing is a skill that is difficult to perfect. Orthodontic appliances protect the dental plaque from the mechanical action of brushing and mastication (Brightman et al., 1991). Patients undergoing fixed orthodontic appliance treatment have elevated levels of Streptococcus mutans (Rosenbloom and Tinanoff, 1991), Candida species and Enterobacteriaceae (Hägg et al., 2004). Undisturbed supragingival plaque initiates gingival Bleomycin Sulfate further leading to gingivitis and gingival hyperplasia (Morrow et al., 1992).
Various chemical agents are used during the active phase of orthodontic treatment to reduce the bacterial plaque accumulation and decrease the occurrence of periodontal disease in these patients. These chemical agents are used adjunctively for orthodontic patients who have difficulty maintaining plaque control by mechanical means alone (Brightman et al., 1991). Some commonly used chemical plaque control agents are chlorhexidine, cetylpyridinium chloride, listerine, triclosan, etc.
Cetylpyridinium chloride is a quaternary ammonium compound and is used in a wide variety of antiseptic mouth rinse products at a concentration of 0.07%. Daily rinsing with cetylpyridinium significantly reduces the clinical evidence of gingival inflammation (Kiszely and et al., 2007). However, the effect of cetylpyridinium used as an adjunct with regular oral hygiene procedures in patients undergoing fixed orthodontic treatment has been lacking.

Aims and objectives

Base line data for the mean gingival bleeding index (Table 1A) mean modified gingival index (Table 1B) and the mean plaque index (Table 1C) show that the three groups were well matched and were the same at the beginning of the study.
Paired ‘t’ test for gingival bleeding index (Table 2A) showed significant difference between pre and post treatment observations at 0.05% and 0.01% level of significance with respect to cetylpyridinium groups and no significant difference were found for the toothbrush/toothpaste group and the control group.
Paired ‘t’ test for modified gingival index (Table 2B) showed no significant difference between pre and post treatment observations at 0.05% and 0.01% level of significance with respect to cetylpyridinium, toothbrush/toothpaste group and the control group.
Paired ‘t’ test for plaque index (Table 2C) showed significant difference between pre and post observations at 0.05% and 0.01% level of significance with respect to cetylpyridinium, and the control group and no significant difference was found for the toothbrush/toothpaste group.
Anova for post treatment gingival bleeding index (Table 3A) among groups showed significant difference among all the three groups. Fcal was found to be greater than Ftab at 0.05 level of significance.