Tag Archives: crizotinib

The proportion of the population exposed to

The proportion of the population exposed to ionizing radiation was estimated by multiplying the number of industries using radioisotopes (from statistics of the Korea Radioisotope Association [27]) with the average number of workers without applying the correction factor. Thus, the exposed population could be either overestimated or underestimated.
In Korea, industrialization started in the 1960s, and the industries using chemicals greatly expanded and operated actively during the 1970s. During these years, the benzene exposure level might have been 5 to 10 times higher than the exposure limits [31]. However, since the 1980s, the working environment has improved, with several laws enacted for occupational safety and health, and most of the important carcinogens are now controlled by exposure limit. From 1980 onward, exposure to carcinogens decreased to a level lower than that associated with the past of other developed countries. Therefore, the PAFs calculated using IARC RRs may be overestimated.

Introduction
Of the various occupational lung diseases, those induced by inhalation of dusts such as asbestos, crystalline silica, and coal are most prevalent. Inhalation of dusts may cause a variety of lung diseases such as coal workers\’ pneumoconiosis (CWP), progressive massive fibrosis, chronic alveolitis, and crizotinib [1]. Notably, crystalline silica has been classified as a class I carcinogen by the International Agency for Research on Cancer [2]. CWP is a lung disease caused by inhalation of coal dust. Once a silica threshold has been exceeded, silica-induced pulmonary disease may progress without further exposure to silica. Clinical detection of CWP, however, is currently dependent on radiological and lung function abnormalities, which are both late diagnostic tools. Identification of accurate and reliable biomarkers would enable earlier detection before irreversible radiological changes in the lung occur [3,4].
Cytokines influence various biological events such as inflammation, metabolic mechanism, cell growth and proliferation, morphogenesis, fibrosis, and homeostasis. Major sources of cytokines in the lung are epithelial cells, endothelial cells, fibroblasts, and inflammatory cells [5]. In previous reports, the relationship between pulmonary inflammation and dusts, and cytokines has been demonstrated for mediators of various toxicological and pathological effects, and several cytokines related with coal dust [6–10]. In one study, the initial concentrations of tumor necrosis factor-alpha (TNF-α) were related to later progression of CWP. Miners who showed abnormally high dust-stimulated release of TNF-α had an increased risk of progression in CWP. TNF-α in pneumoconiosis induced by coal dust was reported to be a powerful tool to estimate individual prognosis of pneumoconiotic disease, even after the end of occupational exposure [11]. Interleukin-8 (IL-8) is a chemokine secreted by a variety of cells types including fibroblasts in response to IL-1 and TNF-α [12]. IL-8 is an important activator and chemoattractant for neutrophils, and has been implicated in a variety of inflammatory diseases [13]. IL-8 is important in the lung inflammation produced by crystalline silica. Both TNF-α and IL-8 were reported to be increased in the supernatant of spontaneous or dust-stimulated monocytes isolated from peripheral blood and in sera of CWP, which did not include progressive CWP [14].
While various studies have addressed the increased production of IL-8 following exposure crystalline silica or coal mine dust in macrophage and fibroblasts, only one human validation study has been published [1]. The available data suggest the importance of IL-8 and TNF-α in CWP. However, little information exists concerning the in vivo relevance of predictive discrimination between the levels of cytokines and progression of CWP. To determine the significance of serum cytokines regard to progression of CWP, a longitudinal design is necessary. However, follow-up studies dealing with the prognostic usefulness of cytokines are scarce in Korea.

Intrahepatic common bile duct sections were noticed in liver samples

Intrahepatic common bile duct sections were noticed in 113/141 liver samples, from 57 P. fastosum infected and 56 non infected cats. Periductal fibrosis (35/57), inflammation (periductal cholangitis, 26/57) and mucous gland hyperplasia (22/57) were the most frequent findings in infected cats. Mild and moderate periductal cholangitis, severe mucous gland hyperplasia, mucosal atrophy/hyperplasia (mild to severe), and mild and moderate periductal fibrosis were the most prevalent bile duct lesions, as shown in Fig. 1.
Assessment of gallbladders’ walls were performed in 126/141 samples, from 58 P. fastosum infected and 71 non infected cats. Among P. fastosum infected cats, most commonly fibrosis (22/58), mucosal hyperplasia (12/58) and cholecystitis (11/58) with mild mononuclear inflammatory infiltration were observed. There was no significant difference in the thickness of the gallbladder walls between infected and non-infected cats. However, the fibromuscular layers in P. fastosum infected cats were significantly thicker (272μm, 114–535μm) than in non-infected (196μm, 95–454μm; p=0.04).
P. fastosum infected cats had a 3.2 fold risk of developing hepatic and biliary changes. A comparison between the microscopic changes in intrahepatic common bile duct and gallbladders is shown in Table 2.

Discussion
In the present study, the overall prevalence of P. fastosum in free roaming domestic cats of 42.6% was the highest prevalence registered in Brazil during the last 52 years (Ogassawara et al., 1986; Ferreira et al., 1999; Gennari et al., 1999; Silva et al., 2001; Ragozo et al., 2002; Mundim et al., 2004; Salomão et al., 2005; Ishizaki et al., 2006; Ramos et al., 2013). We included one of the largest sample sizes in cross-sectional studies, as compared to similar studies; this is the first study using a probabilistic sample size, based on expected prevalence and estimated cat population size.
According to Ferreira et al. (1999), in a previous general helminth crizotinib survey in domestic cats in Rio de Janeiro, in 1963, a prevalence of 45% of P. fastosum was registered. However, many of these observed prevalences could have been higher, if a more sensitive diagnostic method had been used. Bile microscopic egg detection was shown to be 1.6 times more sensitive than manual collection of trematodes by necropsy.
In Mexico, Rodriguez-Vivas et al. (2004) found a similar prevalence of infection in females and males, similar to our study in Maracanaú. In other recent studies from Brazil, the prevalences in females and adult cats were higher (Ishizaki et al., 2006; Mendes de Almeida et al., 2007; Ramos et al., 2013). These authors believed that hunting behavior to feed their offspring may explain the higher prevalence of P. fastosum in female cats. Higher prevalence in adults was expected finding, because the carnivorism habit in kittens expresses from the third to eighth weeks of age (Lovelace, 2006), and the P. fastosum prepatent period is 56–60 days (Maldonado, 1945; Pinto et al., 2015). Therefore, detection of eggs in bile crizotinib would only be possible after 11–16 weeks of age. The older the cat, the higher is the expected prevalence and the fluke burden. No prior primo-infection reports were published.
At clinical examination, more than 1/4 of the cats showed signs of poor nutrition, gastrointestinal and respiratory diseases, skeletal-muscle trauma and neoplasias. Because of the high rate of other concurrent pathologies, it was not possible to perform a suitable assessment of the specific clinical signs. However, rare symptoms of hepatopathy were noticed and there was no significant association of these symptoms (mild jaundice/hepatomegaly) with prevalence of P. fastosum. Most infected cats are usually asymptomatic, and it is known that severe signs depend on the fluke burden and the duration of infection (Basu and Charles, 2014).
Fluke burden was classified as high (>125 flukes), according to Foley (1994). Nevertheless, in previous studies, extreme burdens, as high as, or higher than, 1000 flukes have been observed (Ferreira et al., 1999; Ramos et al., 2013). In Brazil, the highest burden registered in a P. fastosum infected cat was 2553 flukes (Ferreira et al., 1999). In human trematodiasis, the more frequent burden range was 1–50 flukes, but the highest burden was 2946 flukes in a 27 years old male (Sithithaworn et al., 1991). The morphometric measures were in accordance with those compiled by Rodrigues (1963) for P. fastosum.