Tag Archives: cox inhibitor

All experiments are performed at the

All experiments are performed at the same conditions of EMF intensity, frequency, chronical exposure, and temperature. In Table 1, we report the effects of the ELF-EMF exposure on MCP-1 expression in different cell lines.
In HaCaT cells, using RT-PCR we have evidenced a decrease in MCP-1 expression from 4 to 72h in EMF-exposed cox inhibitor with respect to non-exposed cells. This decrease was confirmed by additional Real Time PCR (basal exposed 0.9±0.02 vs. basal non-exposed 1.6±0.05). Also the ELISA immunoassay, performed to evaluate the release of MCP-1, confirmed the expression results. Since it is well accepted that an excessive or prolonged inflammatory response may interfere with wound healing and cause reduction of the inflammatory chemokines by ELF-EMF exposure, represents an interesting and new therapeutic approach in delayed healing.
In SH-SY5Y cell cultures exposed to ELF-EMF, genes involved in the stress response, cell growth and differentiation or protein metabolism have been reported to be generally down-regulated. Genes involved in Ca2+ metabolism, the PI3-kinase pathway are up-regulated. Likewise, key mediators of the inflammatory response appear susceptible to swift modulation, in SH-SY5Y.
MCP-1 is involved in the neuroinflammatory processes associated with diseases characterized by neuronal degeneration. To characterize the impact of ELF-EMF on early ongoing cellular processes, MCP-1 gene expression in SH-SY5Y, was evaluated in the presence and absence of ELF-EMF exposure by RT-PCR. After 24h of ELF-EMF exposure MCP-1 expression was not significantly affected. Albeit our results on MCP-1 expression, despite differences in experimental conditions, are in line with several other ELF-EMF exposure results, while they are not in accord with a study reporting that ELF-EMF promotes cellular neurodifferentiation, as exemplified by neurite extension and number (Falone et al., 2007). In conclusion, our results showed that ELF-EMF exposure is well tolerated and has no relevant impact on MCP-1 gene expression.
The role of MCP-1 in human disease has been demonstrated by immunohistochemical studies in fact the adhesion of cells to the endothelium was induced by expression of adhesion molecules and chemotactic proteins, such as MCP-1. We have analyzed the effects of EMF on the expression of MCP-1 also in THP-1 cells. Since in THP-1 exposed to ELF-EMF no increase in basal levels of MCP-1 was observed, cells were treated or not with LPS and exposed to 50Hz, 1mT EMF for 24hr. Our data indicate that the presence of 10μg/ml of LPS leads to an cox inhibitor increase in expression of MCP-1 in both THP-1 cells non exposed or exposed to EMF. Thus, we hypothesized that MCP-1 mediated THP-1 migration is not affected by EMF exposure, and consequently the exposure to the fields is not a risk factor in diseases in which microglial migration plays a crucial role, such as atherosclerosis, multiple sclerosis and other neuroinflammatory diseases.

The results of in vivo and in vitro studies suggest that EMF may modulate the expression of some inflammatory molecules. The understanding of the influences of EMF on transcriptional events will lead to a better understanding of their mechanisms and to therapeutic interventions for diseases in which these inflammatory molecules play a key role. In spite of the fact that the mechanisms of action of EMF are still under investigation, some authors have supposed that exposure to ELF-EMF affects cell function through mechanical action on both intracellular and membrane proteins, which includes ion channels, membrane receptors and enzymes. All studies agree that the effect of the sinusoidal ELF-EMF varies in relation to cell type and other parameters, such as frequency, flux density and time exposure.
Our data confirm the cell-type dependent effects; in fact we observed increase, decrease or no effect on the MCP-1 expression in different cell lines grown under the same conditions (sinusoidal 50Hz, 1mT, 37°C, 5% CO2).

Other investigations have examined the relationship between wearing

Other investigations have examined the relationship between wearing protective firefighting equipment and balance in an effort to decrease slips and falls with mixed results. A laboratory study of participants walking in the heat while wearing TPC and SCBA reported that the gait spatiotemporal variables such as step length and frequency were not different when comparing the rested and fatigued conditions [17]. Other investigations have reported changes in the gait cox inhibitor when participants cox inhibitor wore TPC of different types compared with baseline conditions [1,18]. One of these studies found that wearing TPC caused the participants to have slower gait and shorter step length, and shorter single leg stance [1]. The wide discrepancy in effects of gear on gait variables may be attributed to a variety of factors including the use of treadmills to control gait speed, the use of obstacles positioned during testing, or possibly an unappreciated factor such as firefighter experience, body mass index, or the type and style of TPC.
In addition to altering the timing of the gait cycle, wearing TPC and SCBA increases postural sway, especially when visual input is eliminated. Functional balance is impaired by wearing personal protective equipment with SCBA as the single most detrimental piece of equipment [6]. Wearing SCBA has been associated with increased fall risk on the fireground [19]. Increased errors in functional gait tests have been reported when participants were fatigued after activity in TPC but this was not seen with the study conditions used in the present report [1].
A previous study of firefighters conducted in our laboratory used the balance test from the present study to examine the effect of wearing different combinations of TPC and SCBA versus regular clothing [12]. Generally, participants in that study decreased gait speed and had more errors on the balance test when wearing TPC and SCBA. The exception was the group that reported regular participation in strength training and aerobic exercise; they maintained gait speed and number of errors across testing conditions. The present study found that participants with higher fitness levels required less time to complete the balance test using linear regression, but did not find a significant difference in time or errors when comparing pre- with postwork conditions.
Minimum aerobic fitness recommendations have been made for the fire service personnel ranging from 10 METs to 14 METs and should be incorporated into firefighter screening and rescreening programs, given the high rates of obesity and the prominence of cardiac death within the fire service [20]. However, there is little evidence that aerobic fitness alone predicts performance on occupation-specific tasks. Persons who have increased fitness levels will experience fatigue less quickly than those who have lower levels of fitness. Fatigue has been noted to impair gait characteristics such as step width and hip and trunk range of motion; gait alterations can increase fall risk [12,17,21]. The regression analysis results in the present report indicate that firefighters with lower fitness levels may have decreased functional balance when compared with their more fit colleagues. However, simple stratification by the 14-MET criterion did not reveal differences in functional balance. It is possible that using a lower criterion would have revealed differences but there were not enough low-fit firefighters in the study to perform additional stratifications. These results support decreased risk of falls in firefighters who adhere to recommended standards for cardiovascular fitness.

Conflicts of interest

This study was funded in part by a grant from the Federal Emergency Management Agency Fire Protection & Safety Program (EMW-2009-FP-00921).

Design of a safety-guaranteed industrial environment is important because it determines the ultimate outcomes of industrial activities involving safety of workers. Looking back over the past 20 years, the industrial accident rate in the Republic of Korea has drastically reduced to less than half of that 20 years ago. Industrial accident rate (IAR) is typically defined as the number of injuries and deaths per 100 workers. Despite the increasing efforts to prevent industrial accidents in recent years, IAR in the Republic of Korea has not improved much beyond a value of 0.7 since 1998 (Table 1). IAR in Japan, however, varied from 0.5 in 1989 to 0.2 in 2009, the average being 0.31 over the past 21 years [3]. Table 2 shows that the fatality rate in the Republic of Korea, as defined by the number of deaths in industrial accidents per 10,000 workers, is from five to 30 times greater than in most developed countries. Note that the UK uses different measures for calculating the accident rate and, therefore, these values in Table 1 are not directly compatible with data in other countries.

It is of interest to compare the significance

It is of interest to compare the significance of cox inhibitor patterns of immune checkpoint–associated molecules on the prognosis of patients with mRCC receiving TKIs as first-line systemic therapy, against other conventional prognostic indicators. In this study, the following independent prognosticators were identified: expression status of PD-L1 for PFS, and expression statuses of PD-1, and PD-L1 in addition to lymph node metastasis and MSKCC classification for OS. Shin et al. [18] also demonstrated the independent prognostic effect of PD-L1, but not PD-L2, expression on both PFS and OS of 91 patients with mRCC who received TKIs. As PD-L1 and PD-L2 both play an important role in immune suppression in the tumor microenvironment [4], it is difficult to clearly separate the effects of these 2 ligands on the prognosis of patients with mRCC receiving TKIs. However, PD-L1 and PD-L2 are known to display different molecular manners in their interaction with PD-1, including their affinity for PD-1 and postbinding conformational changes [21,22].
Another point of interest is whether or not the findings achieved in this study can be applied to future clinical practice. To date, there have been several studies suggesting that therapeutic efficacy of TKI against mRCC could be improved by interfering with immunosuppressive pathways; that is, treatment of various types of cancer model with TKI, which has been shown to increase T-cell recruitment and infiltration into tumors, can be synergistic with immune checkpoint blockade therapy [23–26]. For example, Liu et al. [24] reported that antiangiogenic therapy for mRCC induced the infiltration of CD4+ and CD8+ T-lymphocytes, which was accompanied by up-regulation of PD-L1 and inversely correlated with PFS and OS. Considering these findings in addition to the results of our study, the development of a combined therapy of TKIs and PD-1/PD-L1 blockade may prove beneficial for patients with mRCC, particularly for those with tumors expressing PD-L1.
It is important to acknowledge that there are several limitations to our study. Initially, this was a retrospective study, and the sample size was not large enough to draw definitive conclusions on prognostic issues. Secondly, as widely recognized, findings on immunohistochemical staining of immune checkpoint–associated molecules are likely to experience poor standardization and validation owing to the lack of consensus regarding accurate method, particularly that of suitable specific antibodies and thresholds for judging positivity [20]. Finally, expression statuses of immune checkpoint–associated molecules were assessed in radical nephrectomy specimens alone. However, evaluation of the expression profiles of these molecules in metastatic lesions may be more suitable for investigating the clinical course of TKI therapy. Moreover, previous studies reported a weak correlation between PD-L1 expression in primary and metastatic RCC tissues [27,28], indicating the limitations of assessing heterogeneously expressed molecule solely in nephrectomy specimens.

Informed consent

Ethical approval

The purpose of partial nephrectomy (PN) is to perform complete tumor removal with negative surgical margins (SMs) while preserving the maximum amount of healthy, vascularized renal tissue. Historically, the standard technique of PN involved excising a 1-cm margin of renal parenchyma to achieve a reliable negative margin and minimize the risk of local recurrence. This arbitrary 1-cm SM was introduced in 1950 by Vermooten [1]. However, a recent series report indicated that tumor margin width during PN is not associated with the likelihood of local recurrence. If a negative margin is achieved, even a 1-mm margin width is adequate and oncologically equivalent to a 1-cm margin width [2–5].
Tumor enucleation (TE) consists of bluntly dissecting the pseudocapsule (PC) of the renal tumor along a natural plane from the surrounding tissue without removing a rim of renal parenchyma [6]. In contrast, conventional PN consists of sharply cutting a thin rim of renal parenchyma along with the tumor. Several studies have shown that TE not only is oncologically safe with maximal preservation of renal parenchyma but also appears to provide technical benefits, including reduced entry into the renal sinus, less need for tumor bed suturing, and shorter operative time in cases of T1a renal cell carcinoma (RCC) [6–9]. However, the oncologic safety of TE remains controversial, as the technique could potentially result in a higher rate of local recurrence by inducing a positive SM [10].