The gi function was obtained by considering these minimum and maximum values. The optimization was performed in order to achieve films with higher resistance to break, moderate elongation, and lower solubility. So the weight of gi functions for elongation was reduced and the weight for TS and S was increased. Thus, the gi functions for TS, E,

and S were assigned weights 3, 1, and 3, respectively (Eqs. (18) and (19)): For glycerol films equation(18) G=[(0.6667−1.118X1+0.45X12+0.48X2−0.10X22−0.35X1X23.9)3×(74.73+26.18X1−11.11X12−10.26X2+2.88X22+8.10X1X298)1×(23+7.42X1−8.46X2+2.05X22+5.10X1X243)3]1/3 For sorbitol films equation(19) G=[(0.998−2.70X1+1.09X12+0.80X2−0.47X1X29.5)3×(54.52+30.86X1−7.33X12−6.11X2+7.39X1X282)1×(29.91−7.57X1−7.93X12−9.52X2−4.46X22+5.41X1X248)3]1/3 Optimization of the desirability function (G) for flour films plasticized PLX4032 with glycerol and sorbitol shows that films with greater resistant to break, moderate elongation, and lower solubility can be obtained at Cg, Cs, and Tp values of 20.02 g glycerol/100 g flour, 29.6 g sorbitol/100 g flour, and 75 °C, respectively. To validate the optimization

methodology employed in this work, amaranth flour films plasticized with glycerol and sorbitol were prepared using the optimal formulation. TS, E, and S of the flour http://www.selleckchem.com/GSK-3.html films were measured and compared with values predicted by Eqs. (8), (9) and (10) for

the films plasticized with glycerol, and by Eqs. (13), (14) and (17) for the films plasticized with sorbitol. The values of relative deviations revealed good correlation between the predicted and experimental values (Table 3). Films prepared with the optimal formulation were characterized with respect to solubility as well as mechanical, barrier, and thermal properties; water sorption isotherms; and microstructure. Results are summarized in Table 4. Tukey’s test demonstrated that the amaranth flour films plasticized with glycerol and sorbitol differs significantly in terms of moisture content and solubility (P < 0.05). Glycerol films display higher moisture content after conditioning (58% Resveratrol RH, 48 h), compared to sorbitol films with large sorbitol content. This indicates that glycerol acts as a water-holding agent, while sorbitol acts as a plasticizer with minimum contribution from water molecules. It had been reported that the moisture content of pea starch films also changed little after conditioning when sorbitol was the plasticizer, while addition of glycerol to the latter films promoted a 2–4.5 fold increase in moisture content ( Zhan & Han, 2006). Although glycerol enhances the hydrophilicity of flour films, thus increasing their affinity for water molecules, glycerol films are not readily solubilized in the presence of water, but remain intact even after 24 h.

erytromycyny), uszkodzenie błony śluzowej jelita z objawami zespołu złego wchłaniania, zaburzenia metabolizmu i wchłaniania węglowodanów, zaburzenia degradacji wolnych kwasów żółciowych z następową biegunką sekrecyjną [7, 8,

10, 11]. Do czynników ryzyka wystąpienia biegunki związanej z antybiotykoterapią należą: http://www.selleckchem.com/products/Adriamycin.html długotrwała antybiotykoterapia, szczególnie antybiotykami o szerokim spektrum, hospitalizacja lub pobyt w domach opieki dla przewlekle chorych, wiek <6. r.ż i >65. r.ż., choroby o ciężkim przebiegu, np. wstrząs, mocznica, ciężki stan chorego, zaburzenia odporności, białaczka, leczenie cytostatykami, dializy, zabiegi operacyjne na jamie brzusznej, ciężkie oparzenia, a także epizod przebycia biegunki związanej z antybiotykoterapią [6, 11, 13]. Teoretycznie biegunka związana z antybiotykoterapią może wystąpić po każdym antybiotyku niezależnie od dawki i czasu leczenia, jednak po niektórych antybiotykach (np. aminopenicylinach, szczególnie po amoksycylinie z kwasem klawulanowym, klindamycynie, niektórych cefalosporynach) występuje najczęściej [2, 5]. W polskich badaniach Kotowskiej Pexidartinib i wsp. [14] biegunkę związaną z antybiotykoterapią rozpoznano u 23% dzieci. Najczęściej występowała ona po amoksycylinie, cefuroksymie podanym parenteralnie, amoksycylinie

z kwasem klawulanowym, natomiast nie odnotowano przypadków biegunki w związku ze stosowaniem makrolidów. Przebieg biegunki związanej z antybiotykoterapią może

być różny: od najczęściej występującej, łagodnej i samoograniczającej się biegunki, poprzez zapalenie jelit i/lub okrężnicy, do najcięższej postaci, jaką jest rzekomobłoniaste Resminostat zapalenie jelita grubego [3, 9]. Zapalenie jelit związane z antybiotykoterapią ma przebieg łagodny i ustępuje samoistnie po odstawieniu antybiotyku. W badaniu endoskopowym nie stwierdza się zmian lub występują obrzęk i przekrwienie, rzadko nadżerki. W kale często stwierdza się obecność Clostridium difficile [9]. Nieco cięższy przebieg ma zapalenie okrężnicy. Biegunce towarzyszą bóle brzucha. W posiewach kału często stwierdza się obecność patogennych bakterii, takich jak Klebsiella oxytoca, Clostridium perfringens, Staphylococcus aureus, Candida albicans, Clostridium difficile. W badaniu endoskopowym obserwuje się nadżerki i owrzodzenia głównie w prawej części okrężnicy. Objawy również ustępują po odstawieniu antybiotyku [9]. Najcięższy przebieg ma rzekomobłoniaste zapalenie jelita grubego, występując u 10–20% pacjentów z biegunką związaną z antybiotykoterapią. Wywołane jest przez toksyny A i B Clostridium difficile. Toksyna A, zwana enterotoksyną, ma właściwości cytotoksyczne. Wiąże się z receptorami rąbka szczoteczkowego, prowadzi do rozpadu aktyny, uwolnienia wapnia do cytoplazmy, co powoduje uszkodzenie komórki. Toksyna A jest odpowiedzialna za wystąpienie objawów klinicznych. Toksyna B jest cytotoksyną i może być wskaźnikiem procesu chorobowego [10].

Mechanisms of ROS release here may involve phagocytosis of particles by macrophages and leukocytes with subsequent oxidative burst, but also endocytosis of MNP in epithelial cells (Xu et al., 2009) with generation of ROS,

for example, by iron-catalyzed Fenton reaction or other surface-dependent reactions, disturbance or activation of the respiratory chain (Li et al., 2007 and Xia et al., 2006), interaction with DNA and ROS production directly at the DNA backbone by entering the nucleus (Daniel et al., 1995), or activation of ROS/RNS-producing enzyme systems such as iNOS or cyclooxygenase-2 (Blanco et al., 2007 and Xu et al., 2009) (indirect primary genotoxicity). In this context, the data on OGG1-positive cytoplasm are in line with an selleckchem intracellular generation of ROS and/or RNS, perhaps due to mitochondria-dependent mechanisms such as activation or disturbance of E7080 mw the respiratory chain,

because cytoplasm was OGG1-positive with all particle treatments. Some studies such as that by Xia et al. (2006) identified nanoparticles within or around mitochondria, and Li et al. (2007) demonstrated that inhibition of the mitochondrial respiratory chain function abrogates quartz-induced DNA damage in RLE-6TN rat lung epithelial type II cells. However, they could not demonstrate DNA damage using inhibitors of the mitochondrial respiratory chain only. Mitochondria are the major source of endogenous ROS, with much higher levels of 8-OH-dG in mitochondrial DNA than in nuclear DNA (Souza-Pinto and Bohr, 2002). Thus, there is need of efficient DNA repair, with OGG1 being one of the major DNA repair enzymes in this compartment. The importance of this enzyme is demonstrated by the fact that a “mutator phenotype” with low OGG1 expression/activity seems to be linked to an enhanced risk next for lung tumor development (Paz-Elizur et al., 2003). Mitochondria also represent a major site for intracellular formation

of and reactions with nitric oxide (NO) as a relatively long-lived RNS. Xu et al. (2009) demonstrated production of peroxynitrite anions (ONOO ), which are generated by reaction of NO with SO2− , by incubation of gpt delta-transgenic primary mouse embryo fibroblasts with TiO2 and fullerene nanoparticles. Besides ROS, ONOO is also able to hydroxylate DNA and trigger mutations and tumor development. Mitochondria are thus a central compartment for particle-induced nitro(-oxidative) stress. Subsequent mutations and mutations in mitochondrial DNA are thought to also contribute to tumorigenesis. The lack of differentiation between the particle types concerning occurrence might thus most likely reflect the specific vulnerability of mitochondria to particle-induced oxidative stress and thus an increased demand for the OGG1 enzyme as main repair enzyme for oxidative DNA lesions in these organelles.

It has been reported that increasing glycerol content decreases Tg because the polymer matrix becomes less dense and the mobility of polymer chains is facilitated with the addition of plasticizer ( Mali et al., 2006). This fact was not observed in the present work, since a significant effect was not found (P > 0.05) at Tg in relation to glycerol content. This fact can be related to the same

equilibrium water content presented in all formulations elaborated, (14.11 ± 0.12) g water/100 g of film, since it is well known that water content of a material influenced its glass transition temperature. Fig. 3 shows XRD patterns of BF produced during the second phase. Graph peaks represent inter-layer spacing values and, therefore, they yield information about Bcl-2 inhibitor the crystalline structure

of the analyzed material. It is generally thought that during the intercalation process, the polymer enters into clay spaces and forces apart the platelets, thus increasing the gallery spacing ( Tang et al., 2008). The distance d001 of pure clay (1.44 nm) is typical of hydrated Na-montomorillonite and is lower than the distance observed in the peaks of BF ((1.76 ± 0.01) nm), indicating the uptake of glycerol and/or starch into clay galleries. According to Chen and Evans (2005), many polymers when taken up by montmorillonite produce an expanded structure with d001 ∼ 1.8 nm, therefore it is not clear if starch and glycerol have entered into the clay galleries or just glycerol. Since the BF containing clay

presented peaks, the clay was not completely delaminated, indicating that starch did not enter selleck screening library into all clay inter-layer spacing, which is further supported by lower results for TS when clay was used. Nevertheless, the reduction of water vapor and oxygen permeability values can Fenbendazole also indicate a partial delamination of the clay, which was not detected by XRD. The stacks of clay lamellae (not delaminated) did not contribute significantly to improve tensile properties and could initiate film fracture, which could explain the lower values of TS. The adsorption and intercalation of glycerol into clays is known and has been studied for many years (Hoffmann & Brindley, 1961). In fact, the glycerol used as plasticizer in the BF formulations, could have prevented the entry of starch molecules in the interlamellar spaces of clay and may have covered the entire inter-layer space. However, a non-volatile plasticizer is essential for processing useful starch based materials; without it the mixture of starch and clay powders cannot cohere after the evaporation of water (Chen & Evans, 2005). Glycerol and sugars are plasticizers compatible with starch, improving film flexibility, facilitating its handling and preventing cracks, but it was demonstrated in this study that their presence greatly affected film barrier properties.

, 2005). However, research on antiproliferative compounds has still demonstrated the great pharmacological importance of biological extracts (Clardy and Walsh, 2004, Cragg and Newman, 2005 and Ferreira et al., 2011b). In the last decades, toads have received special attention,

with many publications describing the biological activities of molecules and aqueous and organic extracts obtained from skin glands, whose secretions exhibit bufadienolides, compounds that may act as endogenous steroidal hormones (Schoner and Scheiner-Bobis, 2005) and display antiangiogenic Palbociclib (Lee et al., 1997), antihypertensive (Vu et al., 2006), immunosuppressive (Terness et al., 2001), anti-endometrial (Nasu et al., 2005) and positive inotropic (Cruz and Matsuda, 1993) actions. Herein, we investigated the chemical composition of extracts of R. marina and R. guttatus venoms and their antiproliferative activity in transformed and normal LBH589 cells. Chemical investigations showed significant differences

in composition between R. marina and R. guttatus venoms, in terms of the number and type of constituents. R. marina venom contained four bufadienolides, namely telocinobufagin (1), marinobufagin (2), bufalin (3) and resibufogenin (4) ( Figs. 1 and 2), whereas only one bufadienolide (marinobufagin – 2) was identified in R. guttatus venom. No obvious chemical differences were observed C-X-C chemokine receptor type 7 (CXCR-7) between male and female toads. These compounds have also been identified in other

toad species such as Rhinella schneideri, Bufo bufo gargarizans, Bufo melanosticus, Bufo viridis and Bufo rubescens ( Gao et al., 2010, Cunha-Filho et al., 2010 and Cunha-Flho et al., 2005). There are a number of potential reasons for this variation in venom composition such as species-specific differences, the diet of each species, and environmental factors ( Gao et al., 2010). The chemical profile of the toad venoms (R. marina and R. guttatus) in terms of the number and type of compounds present is mainly determined by the species of origin. Venom extracts from R. marina and R. guttatus (male and female) showed cytotoxic activity against cancer lines after 72 h exposure, mainly R. marina extracts, whose IC50 values were comparable to that of the positive control Dox. According to the American National Cancer Institute (NCI), an IC50 ≤ 30 μg/mL is needed to consider a crude extract promising for further purification and biological analyses ( Suffness and Pezzuto, 1990 and Ferreira et al., 2011b). Previous in vitro analyses have already demonstrated a multiplicity of bufadienolides with cytotoxic potential.

Now let us move to the additional category of statistical formulas based on reflectance (semi-empirical formulas). Figure 6 presents all 83 modelled (synthetic) spectra of the remote-sensing reflectance

Rrs(λ) obtained in this work, with the five selected spectral bands of 445, 490, 555, 645 and 665 nm marked by the grey dashed lines. The absolute values of reflectance or different reflectance ratios at these selected bands were Anti-diabetic Compound Library the subject of subsequent statistical analyses. Of the many different variants of best-fit power functions approximating relationships between the biogeochemical properties of particulate matter and remote-sensing reflectance or reflectance ratios, only those for which the appropriate coefficient of determination r2 between the log-transformed variables were > 0.5 are presented here (see Table 3 and Table 4). It turned out only five of the statistical relationships making use of absolute values of Rrs(λ) (one band formulas) fulfilled the above criterion (see Table 3). These five formulas represent the statistical relationships only between SPM, POM and POC concentrations and Rrs in the red bands of 645 and 665 nm. No relationship between Chl a and the absolute value of Rrs at any analysed band was found satisfactory. Of all the variants presented in Table 3 the best-fit

function, which has the lowest standard error factor X of 1.43, is the one representing the SPM vs. Rrs(645) relationship (see selleck screening library Figure 7). It takes the following form: equation(8) SPM=865(Rrs(645))0.891.SPM=865Rrs6450.891. Note that for the similar relationship in the other red band of 665 nm, the standard error factor X is only slightly worse and is equal to 1.45 (see the second line in Table 3). For the other biogeochemical properties of suspended matter, i.e. for POM and POC concentrations, the respective standard error factors X are evidently larger (at 1.52 and 1.77; see

the third and fifth lines in Table 3). Distinctly better statistical results are achieved when the next group of semi-empirical formulas is considered. Within the group of formulas based on different reflectance ratios many more of the best-fit power functions Ixazomib cost fulfilled the criterion of r2 > 0.5. Table 4 lists 27 different variants of statistical relationships. Among them are formulas using blue-to-red, greento-red and blue-to-green reflectance ratios. However, we may infer from the values of the statistical parameters presented in Table 4 that the best results from the statistical point of view are to be expected when the SPM, POM and POC concentrations are estimated from the same blue-to-red band reflectance ratio (i.e. ratio of Rrs(490)/Rrs(645)). The following three formulas were found (see Figure 8a, b and c): equation(9) SPM=3.85(Rrs(490)/Rrs(645))−1.1,SPM=3.85Rrs490/Rrs645−1.1, equation(10) POM=3.01(Rrs(490)/Rrs(645))−1.03,POM=3.01Rrs490/Rrs645−1.03, equation(11) POC=0.988(Rrs(490)/Rrs(645))−1.

In a test of STM for the color of varying numbers of objects, PFC represented the passage of time across the delay period and the location of to-be-remembered stimuli, but not the colors themselves [17••] (cf [18••]). Consistent with these unit-level findings, MVPA of human fMRI of STM has shown PFC to encode such factors as stimulus category, attentional context, and match-nonmatch status of a trial (e.g., 10•, 19•• and 20••]). Thus, in addition to its well-established role in the top-down control of neural processing (e.g., 14• and 20••]), another function of PFC may be the processing of

information that, although not explicitly being tested, is nonetheless unfolding, and of possible relevance to the organism 17••, 21 and 22]. Patterns of localization OSI-906 clinical trial can also reflect how the brain supports the strategic recoding of information from the format presented at study into one best suited for the impending memory-guided action. One study first presented subjects with a sample object, then, early in the delay, indicated whether memory for fine-grained perceptual details or for category membership would be tested. For the former, MVPA found evidence for delay-period stimulus representation in inferior occipitotemporal cortex, but not PFC; for the latter, the converse was true [19••]. Combining MVPA with univariate

and functional connectivity analyses has revealed a role for frontal cortex and intraparietal sulcus in implementing such strategic shifts of mental coding in visual STM [20••]. MVPA can also track the selleck kinase inhibitor evolution of mental coding in the absence of instructions, demonstrating, for example, that the verbal recoding of visually

presented information also entails the recruitment of a semantic code [26]. Neural data also provide important constraints on models of capacity limitations of visual STM 27• and 28•]. One influential model holds inferior intraparietal sulcus to be important for individuating objects that are to be encoded into visual STM, whereas superior intraparietal sulcus and an area of lateral occipital cortex are responsible for identifying these objects [6]. Recently, however, although the univariate 3-oxoacyl-(acyl-carrier-protein) reductase analyses of data from a follow-up experiment [29••] did reproduce many of the findings from the earlier study, MVPA of the same data failed to support a model of segregated circuits performing these two operations. Instead, the study of Naughtin et al. [29••] produced two novel findings. First, the contrasts intended to operationalize individuation versus identification recruited primarily overlapping regions, thereby calling into question the dissociability of these two hypothesized mechanisms. Second, many regions outside of the intraparietal sulcus regions emphasized by [6] were also sensitive to these contrasts, suggesting that broadly distributed systems underlie the control of visual STM ( Box 2).

polymorpha cultivation http://www.selleckchem.com/products/Neratinib(HKI-272).html activities (e.g., utilization of the zebra mussel biomass in husbandry). The Curonian Lagoon is a large (1.584 km2), shallow (average depth ∼3.8 m) and mainly freshwater coastal body connected to the south-eastern

Baltic Sea by a narrow (0.4–1.1 km) Klaipeda strait (Fig. 1). The Nemunas River brings 98% of the total freshwater runoff and enters the lagoon in its central area, dividing the water body into two different parts (Gasiūnaitė et al., 2008). The northern part is a transitory riverine-like system transporting fresh water into the sea, where salinity may episodically increase up to 5–6 psu during wind driven short-term inflow events. Seawater inflows of 1–6 days duration are most common and the seawater intrusions are usually restricted to the northern part of the lagoon in rare cases propagating ≥40 km into the lagoon. The lacustrine Forskolin purchase southern part is characterized by a relatively closed

water circulation and lower current velocities. Therefore, it serves as a main depositional area of the lagoon (Daunys et al., 2006, Galkus and Jokšas, 1997, Gasiūnaitė, 2000 and Pustelnikov, 1983). Most likely, the zebra mussel D. polymorpha was introduced into the Curonian Lagoon in the early 1800s. The molluscs would have been attached to timber rafts transported via the Central European invasion corridor ( Olenin et al., 1999). However, it may have Florfenicol spread much earlier. According to palaeontological

data, Dreissena could have existed in the Baltic Sea area during the last interglacial, later becoming extinct, before being re-introduced in the early 1800s ( Buynevich et al., 2011 and Starobogatov and Andreyeva, 1994). Zebra mussels are now very abundant in the Curonian Lagoon. They occupy the hard substrates (boulders, embankments, hydrotechnical structures) and soft bottoms (sand, silt or mud) down to 3–4 m depth (Zaiko et al., 2010). The largest area occupied by a zebra mussel community is located in the central part of the lagoon (Gasiūnaitė et al., 2008, Olenina, 1997 and Zaiko et al., 2009). Zebra mussels (D. polymorpha) were collected twice per year, in June and September, in 2006, 2007 and 2008, from two sites within the area of the natural zebra mussel distribution ( Fig. 1). Clumps of mussels were collected manually by wading in the littoral, at 1–1.5 m depth. After collection, mussels were immediately transported to the laboratory, where individual mussels were separated from clumps and frozen at −20 °C until analysis of toxins was performed. Three size classes of the collected mussels were distinguished: <10 mm length, 10–30 mm length and >30 mm length. In total, 108 mussels were collected and analyzed. Sediment core samples were collected from a boat in 2008, July and October.

With this challenge in mind, Otto Graff devoted his scientific work to the field of applied soil biology related to agriculture. He addressed the fundamental question, how earthworms contribute to soil fertility through the decomposition and mineralization of organic matter, the production of nutrient-rich casts or the formation of soil structure and explored how earthworms could be managed by means of crop residues and compost (e.g. Graff 1969). He was among the first who picked up former basic

concepts of Victor Hensen and Charles Darwin (Graff 1983a) to get new insights in the soil ecological significance of earthworms and their role for soil PI3K phosphorylation fertility (e.g. Graff and Aldag 1975) and plant growth (e.g. Graff and Makeschin 1980). His process-related research on ecological

functions of earthworms and their functional diversity filled gaps of knowledge in the range of nutrient dynamics of managed soils (e.g. Graff 1970). At the beginning of Otto Graff’s scientific career it was still the time when soil biologists were mainly restricted to taxonomic research and identification of species with little attention to environmental aspects. Otto Graff was far ahead of his time since he was interested in “ecosystem services of soil biota”, especially earthworms, long before this term became popular. Otto Graff was, however, also interested in earthworm taxonomy. Already in the early fifties, he accumulated his scientific findings in his seminal book on earthworms including selleck compound their distinctive characters, distribution and environmental relevance (Graff 1953). It was this combination of taxonomy and ecology which made his book unique in soil biology. In 1964, Otto Graff submitted his professoral dissertation (Habilitationsschrift) focussing on

soil fauna in tilled soil, to the Faculty of Agricultural Sciences of the Justus Liebig University Giessen where he became honorary professor in 1972. While teaching students in Giessen he continued his scientific check work at the FAL in Braunschweig including supervision of PhD students. In the sixties, Otto Graff participated in the Solling-Projekt of the International Biological Programme (IBP), the first German interdisciplinary programme on ecosystem research. From 1966 until 1970 he served as secretary for the Soil Zoology Committee of the International Soil Science Society. Furthermore, he was chair of the Soil Biology Commission of the German Soil Science Society (1965–1969). Otto Graff organized the Third International Colloquium on Soil Zoology, which was hosted by the FAL in Braunschweig, 5–10 September 1966. In total, 127 participants from all over the world attended. Besides soil zoologists and soil microbiologists also colleagues representing soil science disciplines other than soil biology took the opportunity for trans-disciplinary exchange of ideas.

As células dispõem-se em túbulos e cordões anastomosados (recapitulando os canais de Hering) no seio de estroma fibroso3. Áreas de tipo CHC e de CC são frequentemente observadas na periferia da neoplasia3. http://www.selleckchem.com/products/ITF2357(Givinostat).html Estas

neoplasias são geralmente positivas «para» CK19 (tal como observado no presente caso) e «para» KIT, NCAM e EpCAM (não pesquisados no presente caso). Esta neoplasia tem sido considerada como um subtipo de colangiocarcinoma, mas, de acordo com a classificação atual da OMS (4.a edição, 2010)3, deve ser considerado como uma variante de hepato-colangiocarcinoma combinado, com características de células estaminais, subtipo de colangiolocarcinoma3. Estudos recentes confirmam que as células progenitoras/estaminais hepáticas existem nos ramos mais pequenos e mais periféricos da árvore biliar: os dúctulos e canais de Hering. As células são ativadas quando hepatócitos maduros e/ou colangiócitos são lesados ou inibidos na sua replicação. Trata-se

de células bipotenciais, são capazes de diferenciação quer em hepatócitos quer colangiócitos, dependendo do compartimento celular mais lesado7. Estudos recentes mostram que células estaminais ativadas constituem população alvo da carcinogénese, sendo identificadas em tumores malignos hepáticos, como o CHC, hepato-colangiocarcinoma e o CC, assim como em lesões pré-malignas e adenomas hepatocelulares. Os hepato-colangiocarcinomas combinados sem características de células estaminais têm pior prognóstico e maior taxa de recorrência do que os CHC puros3. A evidência Alectinib manufacturer disponível na literatura é insuficiente para esclarecer o prognóstico MycoClean Mycoplasma Removal Kit dos hepato-colangiocarcinomas combinados com características de células estaminais3. Num estudo clinicopatológico de 6 casos de CLC ressecados, os níveis de α-fetoproteína

estavam ligeiramente elevados apenas em um caso8. Atualmente, o CLC não é um diagnóstico comum não só pela sua raridade, mas também pela circunstância de estas neoplasias poderem apresentar 3 padrões morfológicos no mesmo tumor, o que cria um problema adicional de interpretação, especialmente em biopsias por agulha. A frequência do CLC é muito baixa (0,56% no Japão)9. Neste país foram avaliadas as características clininopatológicas de 9 casos de CLC: 5 destes doentes estavam infetados com VHC, um infetado com VHB e 3 eram negativos para VHC e VHB9. Estes achados sugerem que o CLC se associa à hepatite crónica de etiologia vírica e, em muitos casos, o diagnóstico clínico é de CHC. Os critérios diagnósticos imagiológicos não foram ainda descritos de forma clara, o que faz com que um diagnóstico pré-operatório seja difícil, embora algumas características sugiram que a hipervascularização é uma das características dos CLC9. Os CLC partilham características imagiológicas de CHC e de CC.