gov [9]). Current standard clinical strategies for soft tissue augmentation primarily include the use of synthetic implants and fillers. However, various complications derived from the foreign body, such as capsular contracture or displacement, lead to implant removal or replacement at a relatively high rate. Free fat transfer gives unpredictable results, where graft reabsorption can vary between patients,

although it seems to work well for small defects correction [4]. Mixing autologous ASCs with a portion of suctioned fat and injecting subcutaneously back into the learn more target site is another strategy which is recently used to overcome these problems and to provide a “living scaffold” for stem cells [27]. It has become crucial to develop safe and reproducible protocols for the extraction and storage of ASCs that can adhere to the strict European regulation concerning the Advanced Therapy Medicinal Products (ATMPs). Storage of the SVF could be seen as an intermediary GMP product to be needed in the future for many differentiation protocols to be developed. One step in this direction

is the possibility to store frozen cells for long periods of time in liquid nitrogen and to be able to use them after thawing, i.e. for cell amplification and/or differentiation. We show here that SVF extracted cells can be frozen and thawed without Fulvestrant losing their ability to grow and differentiate in mesenchymal-specific lineages. Only a few studies examined the role of frozen storage of adipose tissue. One of them has recently described the storage of entire adipose tissue at various temperatures for periods longer than 1 year to see whether the tissue was still capable of adipogenic differentiation. Cells isolated from the tissue proved to be a reliable source of human ASCs and adipocytes [11]. Early research studies described a domestic −18 °C storage of adipose tissue for 2 weeks. Injection of fat tissue in nude mice demonstrated the

survival of this tissue as compared to a control group of non-frozen tissue [19]. A simple Cyclin-dependent kinase 3 freezing technique was recently used by storing fat tissues at −196 °C in liquid nitrogen for up to 8 days demonstrating a good maintenance of mitochondrial metabolic activity in the frozen grafts [12]. Remarkably, in both experiments fat tissue samples were frozen without the addition of a cryoprotective agent. Another study reported the use of a cryoprotective agent to better save and keep viable tissues after thawing [26]. Nevertheless, we have to consider that adipose tissue is the source of ASCs responsible for the biological effect observed in regenerative medicine. Thus, for long conservation purposes we should only consider the stromal vascular fraction (SVF) by isolating it from the carrier tissue.

Importantly, CD5 was one of only two proteins identified with at least Palbociclib mw 2 peptides specifically in the VLR32-containing IP compared to the ‘minus-VLR32’ negative control.

The other identified protein, myosin-9 was only identified with 2 spectra from 2 unique peptides, corresponding to a sequence coverage of only 1%. Using this approach we determined that VLR32 immunoprecipitations contained the CD5 antigen (Table 2). We verified these results in parallel experiments testing the reactivity of VLR32 with cells transfected with CD5–GFP fusion constructs, by western blot analysis and immunoprecipitation experiments. VLR32, but not the negative control VLR4, was able to detect CD5–GFP fusion proteins in cell lysates from transiently transfected HEK293T cells (Fig. 3A). This find more reactivity was limited to lysates separated under non-reducing conditions as separation of cell lysates under reducing conditions abolished VLR32 binding (data not shown). In additional experiments, we demonstrated that VLR32 but not the negative control VLR4

precipitated CD5–GFP fusion proteins from cell lysates of transiently transfected HEK293T cells (Fig. 3B) and that VLR32 but not VLR4 stained HEK293T cells transfected with CD5 expression constructs in flow cytometry experiments (Fig. 3C). These experiments demonstrate the CD5-specificity of VLR32. Prior studies of VLR antibodies suggest that binding of the antibody to the antigen is avidity-based and that the affinity of

the individual antigen-binding unit to the antigen is often comparatively low (Herrin et al., 2008 and Kirchdoerfer et al., 2012). To investigate the affinity versus avidity-based binding of VLR32 to the CD5 antigen, we generated monomeric VLR32 antibodies by deleting the C-terminal 42 residues of the VLR antibody. As triclocarban expected, the resulting individual VLR units displayed a slightly faster migration pattern compared to full-length VLR proteins (Fig. 3B). Only the multimeric VLR32 was able to bind to CD5 efficiently as shown for immunoprecipitation (Fig. 3B) and flow cytometry analyses (Fig. 3D). VLR binding was not detected by flow cytometry using the monomeric VLR32 (Fig. 3D) and only a weak signal was obtained for immunoprecipitated CD5–GFP using the monomeric VLR32 (Fig. 3B). These data indicate an avidity-based contribution to the binding of the VLR32 lamprey antibody to human CD5. In this study, we demonstrate for the first time that monoclonal lamprey VLR antibodies can be used for purification and mass spectrometry-based identification of cell surface expressed protein antigens. Unlike conventional immunoglobulin-based antibodies, VLR antibodies utilize their leucine-rich repeats as basic structural units, resulting in a fundamentally different protein architecture of antigen receptors.

Again, there was no effect of experience. At the end of the experiment, we asked the clinicians to answer a questionnaire aimed at their impressions of the utility of the summaries in the clinical setting, especially compared to the traditional records.

Of the 21 clinicians, 19 completed the questionnaire. We asked three forced choice questions: • Did you find the summaries helpful? The responses are shown in Table 7, Table 8 and Table 9 respectively. We also asked them to answer the following questions in their own words: Can you envisage contexts where you would use the summaries? and What things didn’t you like about the summaries? Typical responses are shown MK-2206 in Table 10 and Table 11 respectively: An overwhelming majority of the clinicians reported that the generated summaries were very useful for answering questions about the patients’ condition. They said that, given the opportunity, they would make near constant use of the summaries, mostly by starting with the summaries and then using the records to double check information that they ABT-199 had located with the benefit of the summaries. Clinicians reported a wide range of situations where they would wish to use summaries of the type shown to them in the study. This covered most clinical situations, but the most prevalent examples were ones where important decisions

needed to be made in a short period of time, especially for unfamiliar patients (e.g., in Accident and Emergency (A&E) units, in outpatient clinics and for on-call doctors), for patients who were too confused or in too much pain to provide necessary information and for patients with very complex histories. Some clinicians also noted that the summaries would also help them carry out the more routine parts of their work – for example, they could be “cut and paste” into referral letters. Although the

participating Edoxaban clinicians found the summaries useful, the very fact that as summaries they are necessarily shorter, less detailed and incomplete means that they are not enough to rely on in general for making all clinical judgements. This is as expected. An infrastructure that would allow summaries to be accessible at any time was seen by many to be very important. One of the clinicians also said that the legibility of the summaries was an added bonus, providing medico-legal robustness. She explained that: “We’re often criticised on the legibility of written notes and the failure of clinicians to clearly mark the patient’s name, number and date of birth, plus the date and time seen on each medical incerpt, both because of coherence for anyone reading the notes but also, significantly, when litigation becomes involved. This, in turn, has potential financial implications for the hospital trust.

The peak fractions were

lyophilized and characterized by MS, analytic HPLC and bioassay analysis (Fig. 2D, right). Both toxins’ IC50 values for the different channels were determined, by measuring the extent of peak current inhibition. GTX1-15 is more potent as a TTX-S channel blocker, it has an IC50 of 0.007 μM (h = 1.6) on hNaV1.7 channels (n = 4), 0.12 ± 0.06 μM (h = 1.4 ± 0.4) on hNaV1.3 channels (n = 5), up to 2 μM had no significant effects on hNaV1.5 (n = 4) and 0.93 μM had no effect on hNaV1.8 (5 ± 3%, n = 4) (See Table 1 and Fig. 3A and B). In some cases double peaks were observed such as in Crizotinib nmr Fig. 3B, right. A possible explanation may arise from our observations in ND7-23 which natively express large TTX- sensitive current, alongside exogenously expressed NaV1.8 channels. There, the peak to the left (the lower voltage activated NaV current) is the TTX sensitive component,

while the peak to the right is the NaV1.8 current (data not shown). While using these cells we have used TTX to largely isolate the Nav1.8 current (see Methods section). However, in some cases 600 nM TTX were not efficient in fully inhibiting the low voltage activated component as seen in Fig. 3B and analysis was performed on the NaV1.8 component only. VSTx-3 was also more potent towards the examined TTX-S channels, selleck kinase inhibitor but it is also a potent blocker of NaV1.8 channels. VSTx-3 has an IC50 of 0.19 ± 0.02 μM (h = 1.5 ± 0.2) on hNaV1.3 channels (n = 5), and an IC50 of 0.43 ± 0.14 μM (h = 1.6 ± 0.6) on hNaV1.7 channels (n = 4), up to 1 μM (14 ± 3%, n = 5) had only very small effects on hNaV1.5 and IC50 for hNaV1.8 channel inhibition (n = 5) was 0.77 ± 0.84 μM (h = 0.8 ± 0.04) (See Table 1 Nintedanib (BIBF 1120) and Fig. 3C and

D). Both toxins inhibited the cloned human and rat NaV channels with similar potencies. GTX1-15 inhibited the rat NaV1.3 channel with IC50 of 0.17 ± 0.07 μM (h = 1.3 ± 0.4) (n = 6). VSTx-3 inhibited the rat NaV1.3 channel with IC50 of 0.21 ± 0.04 μM (h = 1.5 ± 0.2) (n = 5) and rat NaV1.8 channels with IC50 of 0.29 ± 0.08 μM (h = 0.8 ± 0.2) (n = 5) (compare to the potency on the human channel in Table 1). Voltage sensor toxin 3 (VSTx3), was originally isolated from the venom of the related tarantula G. rosea, by means of potassium channel voltage sensor affinity column ( Ruta and MacKinnon, 2004)and demonstrated to be a weak inhibitor of the archaebacterial K+ channel, KVAP. In another work GTx1-15 was recently isolated from the venom of the same tarantula, and its effects as a T-type CaV channels ( Ono et al., 2011) or NaV channels ( Murry et al., 2013) blocker were described. Here we describe the isolation of these two peptides from the venom of the P. scrofa spider and their biochemical characterization, chemical synthesis and in vitro characterization as potent sodium channel blockers.

0% for OS while Pem/Plat had higher costs/higher effectiveness versus doublet therapy in 96.3% of the iterations for OS. The characteristics of patients in this study reflect a real-world patient population receiving first-line treatment.

Although PS tended to be good (71% of Pem/Plat patients had a PS of 0 or 1), a relatively large number of patients had a PS of 2+, which differs from the clinical trial setting in which patients with poor PS may be excluded. Despite Pem/Plat patients receiving fewer mean cycles of therapy, PFS was longer for the Pem/Plat cohort compared with Pac/Carbo doublet or Pac/Carbo/Bev triplet; further evaluation is warranted to identify possible drivers of this difference. Longer OS was PI3K inhibitors ic50 observed in patients on Pem/Plat compared with the GDC-0980 mouse doublet or triplet. Similar PFS and OS results were observed in the Pem/Cis cohort compared with the doublet or triplet. A subgroup analysis of patients treated with Pem/Cis (approved combination in the ALIMTA® US Package Insert) showed results similar to those in the overall population of patients treated with pemetrexed plus any platinum. One consideration in using a convenient sample of patients within a single oncology practice network is the potential for selection bias and homogeneity of care (that is, limited generalizability of the results). However, the external validity of this study’s results is supported by the similar outcomes observed

in the phase III clinical trials of first-line treatment for advanced nonsquamous NSCLC [6] and [7]. Several limitations of this study

are acknowledged. No academic or government institutions were included, and therefore these results may not represent resource use and costs in all US practice. Additionally, patients were only followed for one year post index. Patients surviving beyond one year were censored at 1 year, which may have resulted in an underestimation of survival across the cohorts. Also, cost data for this study originated from the PMS data and were limited to outpatient charges incurred within the ION network. As such, we did not have complete cost data across the entire continuum of treatment. For example, charges for inpatient/emergency room services and other specialty care were not available. In conclusion, the data from this study almost fill an important need for information regarding the relative value of these widely used treatment strategies in terms of cost effectiveness. Real-world data from a US oncology practice network in this study show that Pem/Plat can be considered cost effective compared with Pac/Carbo/Bev triplet. In comparison with the Pac/Carbo doublet, Pem/Plat is more costly, but the greater effectiveness and potential incremental clinical benefit may be perceived as more cost-effective, depending on payers’ or society’s willingness to pay. MS, SG, ME and MG received financial compensation for supporting the design and conduct of the study.

Moreover, solid food servings should contain at least 3 g of inulin or oligofructose, or both, for the claim to be made (ANVISA, 2011). Therefore, functional foods for which prebiotic claims can be made must contain a minimum quantity of inulin and oligofructose and be accepted by consumers, as well as being presentable as commercial products. Since inulin and oligofructose have some technological functions, as

described above, it is expected that their incorporation in cakes will cause changes to the sensory attributes of the products, which may also influence their acceptability among consumers. Therefore, the aim of this study was to evaluate the sensory profile and preference mapping of orange cakes with addition of the prebiotics inulin and oligofructose. Inulin and oligofructose/inulin Small molecule library screening were added to orange cakes to obtain functional foods for which prebiotic

claims can be made. The sensory profiles of these Selleckchem BMS 354825 products and of a standard cake (without prebiotics) were obtained by Descriptive Quantitative Analysis. The products were also evaluated for sensory acceptability and preference mapping in relation to three commercially produced orange cakes. The fructans Orafti®GR and Orafti®Synergy1 were provided by Beneo-Orafti, a Belgian company that extracts and produces inulin and oligofructose. Orafti®GR is composed of ≥90 g/100 g of inulin (average degree of polymerization ≥ 10) and ≤10 g/100 g

of glucose + fructose + sucrose. Orafti®Synergy1 is composed, approximately, of 46 g/100 g of oligofructose, 46 g/100 g of inulin and 8 g/100 g of glucose + fructose + sucrose. Beneo-Orafti does not provide degree of polymerizations of inulin and oligofructose present in Orafti®Synergy1. The other ingredients used in cake formulations were purchased in a local market (Carrefour Comércio e Indústria Ltda, São José do 5-Fluoracil supplier Rio Preto, Brazil) and the same brand and specification were used for all formulations. The orange cakes were developed containing sufficient inulin and oligofructose/inulin to obtain functional foods for which prebiotic claims could be made. A standard cake, without prebiotics, was also developed (Table 1). The cakes were prepared under identical conditions. The total fructan content of the cakes with inulin and with oligofructose/inulin, were evaluated in triplicate by means of the enzymatic-colorimetric method (McCleary & Rossiter, 2004) using the FRUCTAN HK kit (Megazyme, Ireland), was 9.0 and 8.3 g/100 g, respectively. These values corresponded, respectively, to 5.4 and 5.0 g of fructans in a 60 g serving of cake, thus enabling prebiotic claims for both products. Three commercial orange cakes were purchased in local market (Carrefour Comércio e Indústria Ltda, São José do Rio Preto, Brazil) to compare the sensory acceptability to the developed cakes.

That is, losses for the Russian Federation include those from its waters in the Baltic and Barents Seas, as well as its Asian waters (and are estimated from the former Soviet Union records in earlier years). The geographic pattern of losses accumulated by the 1970s (Fig. 1a) reflects the distribution of fishing effort in previous decades. By 1945, fisheries in the North Atlantic and North Pacific were already well-developed and contributed nearly equally

to global catch, while those in the southern areas of these oceans and the Indian Ocean contributed just 7% [22]. During the 1950s, most of the Northern oceans came under exploitation [12], and accordingly, 14 of the 15 EEZs registering top losses in the 1970s were Northern hemisphere countries. The only southern country on find more the list, Peru, whose losses were second only to Norway’s in the 1970s, ranked highest in the 1980s (Fig. 1b), due to the severity of the early 1970s collapse of the world’s largest single-stock fishery, Peruvian anchoveta. As fishing effort intensified and spread southward, catches peaked

in the Atlantic by the early 1970s [22], deepening losses for European countries and the US in the 1980s (Fig. 1b). Peru’s losses from the continued depression of anchoveta mounted as well in this decade. In the 1980s, Namibia and South Africa also ranked in the top 15 country losses (7th and 12th, respectively) due to the depletion of the cod-like hake MycoClean Mycoplasma Removal Kit and the small pelagic sardine in their EEZs. The greatest global scale expansion of fisheries took place in the 1980s to the mid-1990s [12]. In European waters, losses appear to have leveled off from the 1980s to selleck products the 1990s (Fig. 1c), likely due to previous depletion and the shift of fishing in and imports from Southern waters. Although dissolution of the USSR in 1991 led to reduced fishing in the waters of its member countries (notably in the Pacific waters off Russia), catches in

the EEZ of the present-day Russian Federation peaked in the early 1980s [6]. Thus, the catch losses for Russia and other Black Sea countries in Fig. 1c may be overestimated, but not greatly. In the Pacific, landings reached their highest level by the late 1980s [22], and Japan and China, 8th and 17th in losses in the 1970s, jumped to 5th and 8th place in the 1990s—significant movement given the head start in stock depletion in European and American waters. Although Peru’s anchoveta landings recovered in the 1990s, overfishing of sardine in the waters off Ecuador and Chile caused these countries’ losses to rise to 11th and 18th place, respectively. Meanwhile, landings in the Indian Ocean, where many stocks are presently under terrific stress, continue to increase [9] so that large losses to overfishing have not yet been tallied (Fig. 1c). However, high levels of underreporting for East African EEZs [25] may contribute to the low losses estimated for these waters.

2 Os autores não proporcionam informação detalhada sobre o protocolo terapêutico e critérios para a suspensão de imunossupressão, o que seria importante pois 6 dos doentes tiveram recaída ALK inhibitor após o tratamento, como é frequente. Apesar destas limitaçõesinerentes à natureza retrospetiva da avaliação e o largo período de observação, o artigo tem o mérito de revelar as dificuldades diagnósticas,

mesmo num centro com elevada motivação em virtude da experiência acumulada em Hepatologia Pediátrica. “
“A hepatite tóxica é uma entidade, do ponto de vista clínico, extremamente desafiante, responsável por uma enorme variedade de manifestações clínicas e um, ainda mais amplo, espetro de gravidade. O diagnóstico de hepatite tóxica exige, aos clínicos,

elevado grau de suspeição e capacidade de avaliação crítica da heterogeneidade fenotípica que caracteriza a hepatotoxicidade. Ainda assim, a imputação da causalidade entre uma determinada droga e a lesão hepática continua a ser uma difícil tarefa, particularmente pelo cenário, frequentemente www.selleckchem.com/products/abt-199.html observado, do doente polimedicado (com fármacos potencialmente hepatotóxicos), pelo utilização crescente de substâncias potencialmente hepatotóxicas como as plantas medicinais e os suplementos alimentares, pela concomitância de fatores de risco ou pela existência de doença hepática Protirelin prévia; isto para não mencionar a elevada probabilidade de impossibilidade de avaliação adequada devido à ausência de critérios diagnósticos rigorosos e uniformes. Acresce a tudo isto,

a inexistência de marcadores específicos e a impossibilidade ética da reexposição. Para além disso, as escalas de causalidade limitam-se à avaliação da relação temporal entre a exposição à droga e a doença hepática e à exclusão de outras causas e a histologia não permite o diagnóstico etiológico. São várias as circunstâncias, como a política farmacológica, os hábitos de prescrição, a etnia, os fatores ambientais e genéticos, que influenciam não só a incidência como a apresentação clínica e a gravidade da doença. A elevada frequência de hepatotoxicidade ao ibuprofeno encontrado no registo espanhol1, a alta incidência de doença induzida pelo nimesulide encontrada na Argentina, Irlanda, Finlândia, Espanha e Uruguai2, o elevado número de casos reportados à nitrofurantoina no registo Americano3 ou aos produtos fitoterapêuticos nos países asiáticos4, são exemplos concretos da variabilidade geográfica. Infelizmente, devido à inexistência de estudos controlados e de estudos completos pós comercialização dos fármacos, publicação preferencial dos casos mais graves e ausência de registo sistemático de todos os casos de hepatite tóxica, a sua verdadeira incidência está subestimada.

To date, some studies have focused on the impacts of crude oil to plankton communities (e.g. Jung et al., 2012 and Varela et al., 2006). Nevertheless, most of these studies have correlative nature and the reported oil spill effects are likely confounded by other environmental variables that are not covered by sampling design. As a consequence, the adverse effect of crude oil cannot often be distinguished (Batten et al., 1998 and Hu et al., 2011). Moreover, most selleck kinase inhibitor of the studies have not investigated the oil pollution induced responses of different

life stages of planktonic organisms although the size of organisms is expected to modulate the responses to the intoxication of biota (Arzate-Cárdenas et al., 2011, Brooks et al., 2003 and Kostial et al., 1978). Cladocerans within the genus Daphnia are one of the key organisms in aquatic ecosystems being an essential link between primary production and many important fish species and at the same time exerting a strong control over phytoplankton abundance ( Lampert, 1987). Daphnia magna is commonly found in brackish water ( Arner and Koivisto, 1993) but also inhabits freshwater environments. Therefore, D. magna is acknowledged as an

important test-organism in ecotoxicological Dasatinib studies both in fresh and brackish waters. Our experiment focused on short-term effects of crude oil on the cladoceran Daphnia magna (Straus 1820) in order to assess the acute effects of crude oil on their survival rate. Furthermore, we explored a potential of different life stages of cladocerans to modulate the effect of intoxication. Previous studies quantified the crude oil effects mainly on the first developmental stages of D. magna (<24 h old in Martinez-Jeronimo

et al., 2005; <48 h old in Ullrich and Millemann, 1983; and <10 days in Ratushnyak et al., 2009) and in one case also mature adults ( Dowden, 1962). The hypotheses of this study are: (1) As an opportunistic species D. magna is not influenced by very low concentrations of crude oil; (2) An increased crude oil concentration decreases the survival rate of D. magna; (3) Different developmental Protein tyrosine phosphatase stages of D. magna have different sensitivity to crude oil, whereat the interactive effect of crude oil concentration and cladocerans’ life stage may dominate over the separate effect of crude oil concentration. D. magna specimens were obtained from continuous cultures maintained for several years at the Estonian Marine Institute of the University of Tartu. The experiments manipulating crude oil concentration and size-classes of the cladocerans were performed at the Estonian Marine Institute. The stock culture was maintained in 20 L aquarium and fed an ad libitum diet of Scenedesmus obliquus. The culture was kept in natural light conditions at room temperature (20 ± 2°C). The cladocerans were separated into three size classes: small (1.4 mm, SE = 0.013; 3 days old), medium (2.5 mm, SE = 0.026; 6 days old), and large (3.1 mm, SE = 0.022; 9 days old).

Thus, we aimed to analyze whether this flavonoid http://www.selleckchem.com/products/PD-98059.html could

be used as medicine to treat brain ischemia. We applied rutin into the acute phase of ischemia and evaluated its bioavailability and its effects on sensorimotor recovery and neurodegeneration. To evaluate whether the administration of rutin after induction of cortical ischemia results in any functional recovery, ischemic animals were treated with rutin and their sensorimotor performance was measured. In cylinder test, statistical analysis showed significant “treatment x day” interaction (F=1.56, p<0.05) and significant effects of treatment (F=3.61, p<0.05) and day (F=16.5, p<0.0001). Comparisons among groups showed more marked recovery in R50 group, and R100 showed discrete effect ( Fig. 1). Thus, rutin

promoted significant recovery of contralateral forelimb performance in support during vertical exploration. EGFR inhibitor Similarly, in adhesive test, statistical analysis showed significant “treatment x day” interaction (F=1.64, p<0.05) and significant effects of treatment (F=5.18, p<0.05) and day (F=30.19, p<0.0001). Comparisons among groups also showed more marked recovery in R50 group than in R100 group ( Fig. 2). Sham animals were also evaluated and showed no significant lost of function ( Fig. 2). Thus, rutin promoted significant recovery of adhesive removal with contralateral forelimb after tactile stimulation. Together, these results suggest that post-ischemic treatment with rutin is effective to recover sensorimotor function after cortical focal ischemia. Since the dose of 50 mg/kg showed better result, it was used in further experiments. Experiments with HPLC showed the presence of rutin in plasma from 2 h to atleast 8 h after i.p. injection, with a peak at 2–4 h (Table 1, Fig. 3). Two equations showed a close fit for obtained data, and both statistic comparisons with F test (equation (1) as the null hypothesis, F=0.09, p=0.77) and Alkaike's Information Criteria (AlCc) (% equation (1)/% equation (2)=17.24) indicated equation (1) (two phase exponential association) as the preferred model ( Table

2, Fig. 3). As previously MRIP shown (Giraldi-Guimarães et al., 2009 and Szele et al., 1995), the procedure of thermocoagulation induced a consistent ischemic lesion that included the six cortical layers, sparing the white matter as revealed by reaction with TTC (Fig. 4). Sham procedure induced no recognizable lesion (Fig. 4). Treatment with rutin promoted no significant reduction of ischemic lesion volume (p=0.65, Figs. 4 and 5). As previously shown (Giraldi-Guimarães et al., 2009), the procedure of thermocoagulation induced large neurodegeneration, as revealed by FJC staining. The majority of FJC+ cells were observed in the core of the lesion (not shown), but a significant number of stained cells was also observed in the periphery of the lesion (Fig. 6).