One of the strengths of this study is that patients had a range o

One of the strengths of this study is that patients had a range of ages and stroke durations; neither of these factors appeared to influence the amount of use or the potential to increase the amount of use with TST. However, this is in

contrast with Lin,6 Fritz,22 and colleagues, who reported age to be a predictor of change in the amount of use after CIMT. The differences may lie in the types of therapy delivered. CIMT is an intense rehabilitation regimen requiring restraint Navitoclax in vivo of the unaffected upper limb and making it essential for patients to use their paretic arm for activities. In contrast, TST (as used in the present study) involved less intense retraining of the paretic limb without specifically inhibiting

use of the less affected arm. It is conceivable that age may affect check details the response to the 2 therapy interventions differently, and this could impact on behavioral change, which has clinical implications for therapeutic provision. There is a substantial amount of research underway to attempt to predict the chance of recovery of arm function after stroke. These results provide further information to guide rehabilitation decisions, providing support for the idea that high functional ability is important for survivors of stroke to report adequate use of the upper limb in activities of daily living. a. SPSS; IBM UK Ltd, PO Box 41, North Harbour, Portsmouth, Hampshire PO6 3AU, England. We thank Tony Christopher and Lindsey Marjoram, BSc, for technical help. “
“In 2011, an estimated 37.9 million people, 12.2% of the U.S. population, were living with a disability.1 The impact of disability is significant. Aside from the enormous direct medical costs related to disability,2 which were estimated at $160 billion in 1994,3 medical problems have considerable personal and societal impact.

Medical costs account for more than 60% of all personal bankruptcies.4 and 5 Government and private payments to support employment-aged individuals Exoribonuclease with disabilities who do not have jobs are also estimated at $232 billion per year.6 These figures may rise with the aging of the U.S. population. With many demographic changes looming, it is important to understand the ongoing impact of disability. Quantifying the national burden of disability is integral to understanding its impact on society and can help direct clinical resources. In addition, given the increasingly limited funding for research, these data may help us direct rehabilitation research funds to specific areas. Toward this end, we have assessed 8 common disabling conditions that might be treated in an inpatient or outpatient rehabilitation setting. Our overall purpose was to (1) characterize the incidence, prevalence, and costs across 8 disabling conditions; and (2) compare the impact of disability attributable to these conditions on activity and work limitation.

The freedom allowed – the Foundation does not impose an agenda up

The freedom allowed – the Foundation does not impose an agenda upon the Vallee Visiting Professor – is perhaps the most desirable attribute

of the program. VVPs are free to use the time however it best suits their objectives (though it has become customary for them to give a public lecture while in residence), and when Jerrold Meinwald came from Cornell in October 1997, the freedom allowed him, among other Daporinad purchase things, to: write first drafts of three chapters for a book; complete or nearly complete four research manuscripts; write and submit a renewal for the NIH grant which supports all my insect related research; and attend several excellent Chemistry Department lectures in Cambridge. For Earl Davie, uninterrupted time was, in many ways, the single most important aspect of my stay at the Karolinska. Free from the usual distractions of telephone calls, administrative duties, and teaching obligations, Earl was able to spend nearly 3 hours every morning thinking and planning both new and old projects underway in our laboratory, which also made it possible to clarify new approaches for our future research. He remembers this time as a very beneficial and exciting experience in my scientific career. In some cases, the Vallee Visiting Professorship changed the direction of the participant’s career. This is perhaps best illustrated by the visit of Klaus Rajewsky. As Klaus approached mandatory retirement age

at the University of Cologne in Germany, it seemed that his career in research would have to come to an end. But, through mutual friends, AG-14699 Bert Vallee became aware of Klaus’

Verteporfin situation and offered him a Vallee Visiting Professorship to explore research opportunities at Harvard Medical School (HMS). As Klaus reflects upon his visit, in the autumn of 1999, my wife and I spent six wonderful weeks in Boston, living in a Vallee-owned apartment…we loved the place, the many friends we made, the electric atmosphere of the medical campus and the general Boston/Cambridge environment. In 2001, we moved to Boston and I became a professor in the HMS Department of Pathology and PI at the Center for Blood Research. The generosity and hospitality of the Vallee Foundation were key to my transatlantic move and to many new bonds and friendships. When Gordon Hammes decided to resume laboratory work after a decade in academic administration, he was offered a Vallee Visiting Professorship. Gordon had been a very successful enzymologist, but after being away from the field for over a decade, wanted to reenter with a new approach. In his words, the professorship was pivotal in getting me started in an entirely new research field: single molecule studies of enzyme catalysis. At Harvard, I was able to talk to many excellent scientists. Most important, I had time to read and think without interruption. Within a year, I had constructed a single molecule apparatus, and my second research career was launched.

The properties measured were tensile strength (MPa), elongation a

The properties measured were tensile strength (MPa), elongation at break (%), and Young’s modulus (MPa). The apparent opacity (Yap) of the films was determined using a colorimeter (BYK Gardner, USA) and was calculated based on the ratio between the

luminosity (L*) of the system (CIELab), which was measured with a black background ( LB*) and a white background ( LW*), and the thickness of the film (φ). The results were expressed on an arbitrary scale (0–100% μm−1) according to Equation BMS-354825 chemical structure (1): equation(1) Yap=[(LB*/LW*)/φ]×100 The opacity of the films intercalated with fresh pasta was determined after 2 and 37 days of storage at 10 °C. Water vapour permeability (WVP) was determined gravimetrically, according to the ASTM E96-00 (1996) and under a relative

humidity gradient of 33–75%. The tests were conducted in duplicate. The yeast and mould counts in fresh pasta were taken in Dichloran Rose Bengal Chloramphenicol (DRBC) agar incubated at 24 °C for 5–7 days; coliform bacteria, which were grown at 45 °C, were counted using the most probable number method (MPN) (APHA, 2001, p. 676). The water activity of the fresh pasta was determined using an Aqualab CX2T equipment (Decagon Devices, USA) at 25 ± 2 °C, and the moisture content (on a wet basis) was determined according to the procedure described in the AOAC 925.04 (1995). Analyses were performed in duplicate. The colour parameters L*, a* and b* (CIELab system)

of the fresh CHIR-99021 clinical trial pasta were determined using a colorimeter (BYK Gardner, Germany) with an illuminant D65 (daylight) and a visual angle of 10°. The ΔE values (i.e., the colour difference between two spectrophotometric measurements) were calculated according enough to Equation (2): equation(2) ΔE=(Lt∗−L0∗)2+(at∗−a0∗)2+(bt∗−b0∗)2where ‘t’ represents a specific storage period and ‘0’ is the beginning of storage. The reference sample was the pasta in the beginning of storage (t = 0). The sorbic acid content in the fresh pasta was assessed by ultraviolet absorption spectrometry (UV) at 530 nm AOAC 975.31 (1995). The results of mechanical properties, colour parameters, opacity and water vapour permeability were analysed using analysis of variance (ANOVA); treatment means were compared using Tukey’s test and Student’s t-test at a 5% significance level (p < 0.05) using a Statistica 8.0 software (Stat-Soft, Tulsa, OK, USA). The opacity of all films containing potassium sorbate (Fig. 1) was lower than that of the control films (CF), most likely due to the presence of sorbate, which acted as a plasticiser, thereby allowing a higher mobility between the starch molecules, and the passage of electromagnetic radiation. The FS4.5 film became more opaque during storage, most likely due to starch retrogradation.

, 2000) The amino acid sequences were retrieved from the Univers

, 2000). The amino acid sequences were retrieved from the Universal Protein Resource Knowledgebase (www.uniprot.org) or the Worldwide Protein Data Bank (www.pdb.org). Ts2 (Uniprot ID P68410) contains 62 amino acids, including 8 cysteine GDC-0449 solubility dmso residues ( Mansuelle et al., 1992). The peptide has a theoretical molar mass of 6998.0 Da and a pI of 7.70 (http://web.expasy.org/protparam/). Ts2 is a sodium channel inhibitor α-neurotoxin that

inhibits the rapid inactivation of NaV1.2, NaV1.3, NaV1.5, NaV1.6 and NaV1.7, but does not affect NaV1.4, NaV1.8 or DmNaV1 ( Cologna et al., 2012). The overall structure of the Ts2 model consists of three β-strands and one α-helix that are arranged in a triangular shape forming a cysteine-stabilized α-helix ⁄ β-sheet (CSαβ) motif ( Cologna et al., 2012). While Ts6, also called TsTX-IV ( Arantes et al., 1989), acts on K+ channels ( Coronas et al., 2003). Ts6 (Uniprot ID P59936) contains 40 amino acids, including 8 cysteine residues ( Pimenta et al., 2003).

The theoretical molar mass and pI of the peptide are 4514.2 Da and 8.50, respectively (http://web.expasy.org/protparam/). Ts6 is a potassium channel toxin alpha-KTx 12.1 that inhibits high conductance calcium-activated potassium channels ( Novello et al., 1999) and weakly inhibits Shaker B potassium channels ( Coronas et al., 2003). The structure of the peptide consists of an alpha-helix connected to a triple-stranded beta-sheet stabilized by four disulfide bonds ( Oyama et al., 2005). GDC-0068 molecular weight Our group has previously demonstrated that following stimulation with Ts1, Ts2 or Ts6, the in vitro release Cytidine deaminase of inflammatory mediators by peritoneal macrophages (J774.1) is independent of the action of these toxins on ion channels ( Zoccal et al., 2011). Several reports demonstrated that cytokines are increased after envenomation. Magalhães et al. (1999) observed an increase of interleukins (IL)-1α, IL-6, Interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum of patients who were stung by T. serrulatus. Furthermore, the increased

levels of GM-CSF in severe envenomation might be involved in neutrophilia induced by T. serrulatus venom ( Magalhães et al., 1999). The synthesis of anti-inflammatory cytokines, such as IL-10, was also observed in the plasma of patients with both moderate and severe cases of envenomation ( Fukuhara et al., 2003; Petricevich, 2010). Scorpion venoms can stimulate the immune-neuroendocrine axis by inducing the release of catecholamines, corticosteroids, bradykinin ( Chaudry et al., 1989; Sofer et al., 1996; Magalhães et al., 1999; Pessini et al., 2003) and eicosanoids mediators, such as prostaglandin (PG)E2, lipoxin A2 (LXA2) and leukotriene (LT)B4 ( Nascimento et al., 2005; Teixeira et al., 1997).

The soil column was placed in an 80 cm deep square

pit fi

The soil column was placed in an 80 cm deep square

pit filled with soil both inside and outside the column and made soil compact by watering. The distance between soil columns was 11 cm, that is, the row width was 65 cm, and surrounded by the board rows (Fig. 1). Two plants VE-822 molecular weight were grown in each soil column. Plants in one column were planted under normal spacing (NS, 27 cm), and the other under narrow spacing (CS, 6 cm). The columns were treated at two nitrogen levels, N0 (no N) and N1 (7.5 g N plant− 1), and for the N1 treatment, nitrogen fertilizer was applied by 20%, 50% and 30% at the seedling, male-tetrad and flowering stages, respectively. The experimental design included four treatments Sorafenib cell line (N0 × NS, N0 × CS, N1 × NS and N1 × CS) and 30 separate soil columns were planted in each treatment. Samples of the soil columns (top 40 cm) were mixed and screened with 20 mesh sieving. Then they were mixed

with clean river sand in a ratio of 3:1 by volume of topsoil to sand. The mixed soil nutrient contents were as follows: organic matter 7.1 g kg− 1, total nitrogen (N) 0.62 g kg− 1, mean available mineral phosphorous (P) 46 mg kg− 1, and exchangeable potassium (K) 59 mg kg− 1. All treatments were fertilized with P and K according to nutrient demand, and each unit of experimental treatment was fertilized with 2.5 g of phosphate (P2O5) and 6.25 g of potash (K2O), with both applied at the seedling stage. Required irrigation was also applied from the outlet of a pump by using plastic pipes. At the onset of pollination, three replicates of each treatment were sampled on the same day fortnightly. The above-ground plant parts were divided into leaves, grains and stems (remaining parts except for leaves and grains). Roots were separated from various layers of the soil profile, viz. 0–20, 20–40, 40–70 and

> 70 cm, and washed to remove all soil residues. Root layers were mixed well after removing impurities, and fine roots were selected and temporarily stored at 0 °C. 2,3,5-triphenyl tetrazolium chloride (TTC) reduction was applied to determine root reductive activity [19]; fresh root samples (0.5 g) were exposed Thymidylate synthase to 0.4% TTC and 0.2 mol L− 1 tricine-HCl buffer (pH 8.4), then placed in a darkroom at 37 °C for 6 h to induce reduction of TTC to triphenyl formazan (TTF), following the method described by Duncan and Widholm [19]. To quantify the amount of TTC reduced, we extracted the tissues with 95% ethanol at room temperature for 48 h, and then performed spectrophotometric analysis at 485 nm. The results were expressed as μg TTF g− 1 root mass h− 1. At maturity, the remaining aboveground parts were completely harvested to calculate average dry matter weight per plant and weight distribution. The remaining roots and above-ground samples were fixed at 105 °C for 30 min. Samples were subsequently baked at 75 °C until a constant weight was reached and recorded.

The analysis is extended to more depth ranges and we compute
<

The analysis is extended to more depth ranges and we compute

MPTRCMPTRC in 100 m bins. The depth of the bin with the highest tracer mass gives ZPTRCZPTRC which is plotted against ΔPEΔPE in Fig. 14. The correlation between ΔPEΔPE and ZPTRCZPTRC (black bullets) shows very little scatter and indicates a functional relationship B-Raf inhibition between the potential energy gain and the depth of penetration. With increasing potential energy in the system the plume is capable of first breaching the 200 m then the 500 m density interface in the ambient water. The abrupt transition from arrested ( ZPTRC≈500m) to piercing ( ZPTRC≈1500m) can be explained by the lack of stratification in the bottom layer. In most experiments where the plume breaches the AW-NSDW interface it also continues to the bottom of the slope after flowing through a homogenous layer of NSDW. Using the buoyancy flux of a density current, a concept similar to the flux of potential energy, Wells and Nadarajah (2009) reported a functional dependence between the intrusion depth

Z   buy Dapagliflozin of a density current and the geostrophic buoyancy flux Bgeo=g′VNofhBgeo=g′VNofh (where h   is the initial height of the flow from a line source), the entrainment ratio E   and the ambient buoyancy frequency N   as Z∼E-13Bgeo13/N. However, their results are not readily applicable to our model which has non-linear ambient stratification with sharp density interfaces causing N   to Urease vary during the plume’s descent. Neither is E   constant during our experiments. In Fig. 14 we also

plot the plume height hFhF (red stars) against the potential energy gain ΔPEΔPE. It shows high hFhF in runs with low ΔPEΔPE (those runs where the plume is arrested in the Atlantic Layer), and a low hFhF in high-ΔPEΔPE runs when the plume spends little time transiting the AW and flows straight through to the NSDW layer. The slow but steady rise in PE   in Fig. 12 may suggest that any addition, however slow, of dense water (and thus potential energy) could eventually lead to the piercing regime if the initial SFOW density is greater than the density of the bottom layer (which is the case in our setup for S   > 34.85). Under this assumption the ΔPEΔPE-axis in Fig. 14 can be taken as a proxy for time. As time progresses (and ΔPEΔPE increases) the entrainment ratio E   reduces (i.e. hFhF shrinks) as the plume moves from the Atlantic Layer into the deep NSDW layer. When a certain threshold is passed, the plume has modified the ambient water sufficiently such that subsequent overflow waters pass through the AW relatively unimpeded (with less dilution) and penetrate into the deep waters. There is a caveat though, which works against the plume’s piercing ability.

Thus, corporations would often accompany alternative testing meth

Thus, corporations would often accompany alternative testing methods with more historical animal-based methods ( Stephens and Mak, 2013).

In order to move away from this status quo of toxicity testing, it is important to have an understanding of regulatory testing requirements and assessment and why they were developed ( Fowle et al., 2013). Numerous regulatory GSK-3 inhibitor authorities and systems exist worldwide for the assessment and classification of potentially hazardous substances. Their principal objective is to assess the hazardous potential of substances that may come into contact with the eye in order to supply regulations, guidelines and recommendations for their safe use. This offers consumers or the end user protection via the communication of hazardous information and protective measures ( ICCVAM, 2010b and Wilhelmus, 2001) to prevent misapplication and to minimize accidental Pexidartinib mouse exposure. Regulatory assessment is based upon “informed decisions” that are

not purely scientific in nature. They have to take into account congressional directives, legal precedent, benefit/cost considerations and public values ( Fowle et al., 2013). This sometimes frustrates scientists, alternative-testing supporters and stakeholders alike, since “good science” does not always drive decision making ( Fowle et al., 2013). EURL-EVCAM aims to promote scientific and regulatory acceptance of non-animal tests. Similarly, ICCVAM is an interagency committee made up of 15 US Federal agencies including the Consumer Product Safety Commission (CPSC), National Institute for Occupational Safety and Health Administration (NIOSHA) and the FDA. ICCVAM aims to facilitate the development, validation and regulatory acceptance of new and revised regulatory test methods that reduce,

refine and replace the use of animals. It was originally developed as a committee Cyclin-dependent kinase 3 of the National Committee of Environmental Health Sciences (NIEHS) in 1997, and was made permanent in 2000 under NICEATM. Since then ICCVAM has contributed to 63 alternative testing methods, 38 of which do not require live animals, although not all of them are concerned with ocular tests. Several directives restrict and even prohibit the use of animal testing, for example the Amendment of the Cosmetic European Directive (2003/15/EC) imposed a ban on the use of animals for the testing of cosmetics and their ingredients. However, until recently companies could still market products that had been animal tested outside of the EU. A new cosmetic regulation replaced the Cosmetics Directive in 2009 (Regulation (EC) No. 1223/2009) and since July 2013, cosmetics and cosmetic ingredients tested on animals can no longer be sold in Europe, even if they have been tested elsewhere. This has promoted considerable progress in replacing animal models for chemical toxicology (Alépée et al., 2013).

2) Analyses ware conducted using a gas chromatograph (Agilent Te

2). Analyses ware conducted using a gas chromatograph (Agilent Technologies, GC 6890A) coupled to a Mass Selective Detector (MSD 5973 inert) from the same company. VOCs were resolved using a β-cyclodextrin capillary column (CYCLODEX-B, 30 m long, 0.256 mm ID, 0.25 μm film thickness) supplied

by Sigma Aldrich (Taufkirchen, Germany). The internal coating was composed of a permethylated β-cyclodextrin dissolved into a cyanopropyl-dimethyl polysiloxane selleck chemicals llc liquid. Glass inlet liners with a narrow internal diameter (0.75 mm ID) were supplied by Sigma Aldrich (Taufkirchen, Germany). A Merlin microseal septum and a microseal nut (Sigma Aldrich, Taufkirchen, Germany) were used to ensure gas integrity against leaks during the time of injection. Seawater samples of marine VOCs were taken during a mesocosm CO2 enrichment study conducted in a Norwegian Fjord, close to the city of Bergen. Nine flexible, polyethylene enclosures (2 m diameter, 25 m length, details in Riebesell et al., 2012) containing unfiltered fjord water were moored off-shore of the Raunefjord (60° 15′ 40″

N, 5° 12′ 0″ E, water depth: 80 m). The partial pressure of CO2 (pCO2) in the seawater of each enclosure was modified by injecting CO2 saturated seawater. VOC concentrations of low (280, 280, 360 μatm), middle (560, 840, 1120 μatm) and high pCO2 (1400, 2000, 3000 μatm) treated mesocosm enclosures were monitored for a period of 29 days. Fertilization with nitrate and phosphate was used (day 14) to instigate a phytoplankton bloom growth. selleck screening library Depth integrated water samples (0–12 m) were collected

daily using 5 L polyethylene aspirators (Hydro-Bios). Resminostat Gentle rotation of the aspirators (post collection) ensured sample homogeneity. Directly after collection, sub-samples were decanted into air-tight, UV protected glass bottles, using Teflon tubing. Bottle and tubing were initially rinsed with sample water. Then, the tubing was placed at the bottom of the bottle which was allowed to overflow briefly and thereafter capped. In this way, the effect of water–air contact was minimized to almost zero (bubble-free collection). The analysis of samples was completed on the same day as collection. The samples waiting analysis (maximum 8 h) were kept in the dark and under cool (ca. 4 °C) conditions, approximately same as present in the fjord. In this way, sample instabilities due to biological activity were minimized. The needle trap sampling system is based on purging gases from water samples onto a needle trap device, as shown in Fig. 2. A fixed 10 ml volume was used for all water samples. Seawater samples were introduced into the purging glass tube, through the water inlet port (part 8, Fig. 2), using a 10 ml water sampling syringe. The tip of the syringe was placed at the bottom of the bottle straight after the sample was opened and then immediately into the inlet port of the sampling system.

A doente manteve metrotexato e prednisolona e iniciou messalazina

A doente manteve metrotexato e prednisolona e iniciou messalazina, ficando clinicamente estabilizada durante alguns meses. A decisão de iniciar messalazina

é questionável já que o seu benefício na DC não está suficientemente demonstrado9 and 10; admite-se que alguns subgrupos de doentes possam ter benefício11 e na prática Nutlin 3a clínica corrente ainda é muito utilizada. A posologia do metotrexato está abaixo da recomendada para a DC, mas admitiu-se que o uso simultâneo de corticosteroides assegurava a imunossupressão. O posterior agravamento clínico, com astenia, anorexia, perda ponderal importante, náuseas e o aumento marcado da massa na FID num curto espaço de tempo, poderia até ser interpretado como um agravamento da atividade da DC; mas se os achados radiológicos da primeira enterografia sugeriam processo inflamatório ativo, em concordância com a impressão clínica, já a segunda enterografia

sugeria fortemente a presença de processo atípico do cólon, o que desde logo impunha uma reavaliação endoscópica e histológica. Foi realizada nova colonoscopia que mostrou aspeto inflamatório exuberante e ulcerações no ascendente distal condicionando estenose não franqueável (fig. 3). No transverso viu-se úlcera longitudinal extensa (fig. 4) com aspeto inflamatório, ocupando metade do lúmen, numa extensão de 15 cm. A histologia mostrou mucosa intestinal com extensas áreas ulceradas small molecule library screening infiltradas por tecido de granulação, sem lesões causadas por micro-organismos, sem sinais de efeito citopático viral. Alguns fragmentos do cólon transverso estavam infiltrados por

toalhas de células redondas com imunorreatividade com CD20 e CD10 e não reativas com CD5, CD3, Bcl2 e ciclina D1, achados compatíveis com linfoma não-Hodgkin B difuso de grandes células. Foi referenciada para a consulta de hematologia onde a doença foi estadiada e classificada como estádio iv B. Protelou-se terapêutica cirúrgica devido ao mau estado geral da doente e à presença de trombose venosa profunda extensa no membro inferior esquerdo. Suspendeu metotrexato Demeclocycline e realizou 7 ciclos de quimioterapia com esquema R-CHOP (rituximab, ciclofosfamida, doxorrubicina, vincristina e prednisolona) com remissão completa até ao presente (17 meses). Os aspetos endoscópicos das 2 colonoscopias, realizadas com 2 anos de intervalo, diferiam bastante. No primeiro exame, a mucosa ileal congestionada com erosões aftoides era evocativa de DC. No segundo exame, o processo inflamatório exuberante da porção proximal do cólon com estenose poderia corresponder a uma atividade marcada da DC ou a um adenocarcinoma. A úlcera extensa do transverso, associada a congestão da mucosa, favorecia a DII, visto não corresponder ao aspeto mais habitual do adenocarcinoma cólico. A histologia revelou o diagnóstico final de linfoma B difuso de grandes células.

No entanto, algumas destas vantagens são estatisticamente modesta

No entanto, algumas destas vantagens são estatisticamente modestas, escasseiam Selleckchem NU7441 análises de longo prazo e muitos dos estudos provêm de um mesmo centro. Acresce que os doentes que continuam a terapêutica regular poderão vir a desenvolver efeitos colaterais, ter de parar o fármaco por falência secundária, ou seja por perda de efeito terapêutico, o que ocorre em cerca de 30 a 40% dos doentes no primeiro ano de tratamento, ou por não adesão ao tratamento (falta de «compliance»),

que acontece em um terço dos doentes5. Também não está definido se os doentes devem ser tratados com biológicos em monoterapia ou conjuntamente com IM. Os argumentos oscilam entre a necessidade de otimizar NVP-BKM120 molecular weight a terapêutica anti-TNF e o aumento do risco de complicações. O recente estudo SONIC favorece a associação de IFX+IM, todavia com um aumento assinalável do risco de linfoma hepatoesplénico. Num inquérito nacional efetuado nos EUA cerca de 38% dos gastrenterologistas que prescreveram IFX não continuaram com tratamento de manutenção13. Na Europa alguns centros continuam a usar a terapêutica episódica na consecução de uma estratégia IM, em grande parte por razões financeiras5. Na prática clínica temos verificado que a paragem de IFX, nos doentes em remissão e

com terapêutica IM concomitante, não é, geralmente, seguida de recidiva e quando tal sucede a reintrodução de IFX é eficaz e bem tolerada. A mesma constatação tem sido reportada em diversos estudos reumatológicos. Outra questão controversa é a duração do tratamento com anti-TNF na DC. Consideram muitos prestigiados gastrenterologistas, nomeadamente da European Crohn’s and Colitis Organization (ECCO), que a terapêutica deve ser regular e mantida por tempo indefinido14. A terapêutica apenas poderá ser suspensa observando-se evidência endoscópica de cicatrização da mucosa, PCR normal e ausência de fatores de prognóstico adverso, tais como, doença extensa do intestino

delgado, tabagismo, ou doença perianal fistulizante5. No estudo «STORI», foi verificado que a paragem do tratamento após profunda remissão, caracterizada por hemoglobina superior a 14,5 g/dl, PCR alta sensibilidade normal e endoscopia totalmente normal, tem probabilidade de ser bem sucedida5. Este procedimento não é seguido no Reino Unido, Progesterone onde a terapêutica biológica é muito menos utilizada do que nos países vizinhos1. De facto, a British Society of Gastroenterology e o «NICE 2010 guidance» aconselham a terapêutica com IFX ou adalimumab até um limite máximo de 12 meses, desde o início do tratamento1 and 7. Este apenas poderá ser continuado se houver boa evidência de doença ativa expressa pelos sintomas clínicos, pelos marcadores biológicos e investigação, incluindo endoscopia se necessário. Os doentes que continuam o tratamento devem ser reavaliados cada 12 meses e, em caso de recidiva após paragem, podem ter a opção de o recomeçar.