Things are better if bivariate or multivariate analyses are carri

Things are better if bivariate or multivariate analyses are carried out. Knowing that two characters have a strong genetic correlation tells us that at least a part of the pathways leading from genotype to phenotype are shared and that a functional relationship may exist between the variables being studied [32]. Indeed, if one peruses recent issues of the journal Behavior Genetics (where a large part of human quantitative-genetic research is published), it becomes

rapidly evident that bivariate and multivariate analyses find more have become the norm and that authors strive to uncover functional relationships between different behavioral phenotypes by investigating genetic correlations (see, e.g., [33]). In addition, human behavior geneticists are starting to follow the example of psychiatric geneticists and are attempting to localize genes involved in the regulation of behavior, with up till now equally mixed results, however (e.g., 34 and 35]). Gene localization, unfortunately, is remaining an elusive goal in human behavior genetics. Whereas classical linkage studies were (and PS-341 datasheet are) powerful tools to find genes for monogenic disorders, they have dismally failed to help us

identifying genes involved in either normal or pathological behavior. However, since the completion of the human genome project, Genome-Wide Association Studies (GWAS) are helping gene identification for polygenic disorders and have been particularly successful in non-mental disorders like cardiovascular disease (e.g., [36]). The first positive results are coming in for psychopathologies but huge sample sizes were needed before the first genomic risk loci could be identified [37]. Recent efforts to identify genomic risk loci involved in schizophrenia have used total sample

sizes (including controls) of up to 150 000 subjects [38]. In principle, of course, there is not really any reason to divide behavior genetics into human and animal studies. In practice, however, the ability to manipulate populations and to carry out directed breeding means that the field has advanced much farther in animal species. Other articles in this issue will present results obtained with fruit flies, worms, and fish. Here I concentrate on mouse studies. As in humans, animal behavior genetics used to be Methocarbamol heavily oriented towards quantitative genetics, using such designs as the classical Mendelian cross [39] or the diallel cross 40 and 41]. In addition, however, selection studies and comparisons between inbred strains often allowed research into the neural mechanisms underlying behavioral differences. Already in the late sixties and early seventies, the pharmacogenetic experiments of van Abeelen referred to above allowed him to conclude that C57/BL6J mice had a hippocampus that functions more effectively than that of DBA/2J mice (for a review, see [10•]), a conclusion confirmed many times since. Since then, many new tools have become available to study the genetics of behavior.


and 4 8 ± 0 5%, respectively) in comparison with negat


and 4.8 ± 0.5%, respectively) in comparison with negative control (94.3 ± 1.5%, viable cells; 1.7 ± 0.9%, early apoptosis and 1.5 ± 0.2%, late apoptosis) (p < 0.05) ( Fig. 5B). Similarly, Dox also caused a significant cell viability decreasing (16.1 ± 0.1%) and early apoptosis rising (83.2 ± 0.1%). Another early marker of the apoptotic process is the depletion of mitochondria membrane potential. In this work, none of the compounds evaluated in 24 h of treatment significantly alter the mitochondrial membrane potential (p > 0.05), suggesting that only the extrinsic pathway was activated within 24 h. However, in 48 h exposure, compound 4 (2 μM) caused depolarization of mitochondrial membrane potential (37.3 ± 4.6%, Fig. 5C) when compared to negative control (4.7 ± 0.6%, p < 0.05). Dox, positive control, cause selleck compound see more intense membrane depolarization after 24 h (44.0 ± 2.3%) and 48 h (46.9 ± 5.4%) of incubation. The DNA damage induced by the α-santonin derivatives was evaluated in human mononuclear cells. DNA damages were not detected with the concentrations tested (p > 0.05, data not shown). Sesquiterpene lactones (SLs) are plant-derived compounds often used in traditional medicine against several human diseases such as inflammation and cancer (Ghantous et al., 2010). Previous researches showed no cytotoxic activity of the α-santonin molecule, even at high concentrations (100 μM) (Kim et al., 2002 and Konaklieva Selleck RG7420 and Plotkin,

2005). Then, we designed three cytotoxic sesquiterpene lactones based on α-santonin (Arantes et al., 2009; 2010) with activity on different cancer cell lines and low toxicity on PBMC. In this work, we propose the mechanism responsible for this cytotoxicity using the HL-60 cell line as experimental model and the compounds tested (1 and 2 μM) after 24 h of treatment. Initially, we showed that the antiproliferative potential of the α-santonin derivatives is not related to direct

membrane damages, since the trypan and propidium iodide exclusion techniques did reveal membrane permeability of remaining cells. In fact, it is possible that apoptosis or other process might have already compromised cell proliferation, but membrane integrity is still maintained (Kepp et al., 2011). We previously reported that these derivatives did not produce cell membrane disruption of mouse erythrocytes (Arantes et al., 2010). Some studies have been pointed that SLs inhibit tumor growth by selective alkylation of growth-regulatory biological macromolecules, such as DNA and key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which leads cells into apoptotic death (Fernandes et al., 2008 and Rozenblat et al., 2008). Herein, all molecules reduced BrdU incorporation by HL-60 treated cells, suggesting inhibition of DNA synthesis. Other SLs caused inhibition of DNA synthesis by BrdU test such as enhydin, uvedalin and sonchifolin (Siriwan et al., 2011).

29 ± 1 0 versus 12 12 ± 1 1 g, P < 0 001; Fig  1B) At the end of

At the end of the experiment, the organs were dissected out and weighed. The META060 supplementation decreased gonadal (1.17 ± 0.2 versus 2.40 ± 0.09 g, P < 0.001) and subcutaneous (0.47 ± 0.09 versus 1.53 ± 0.2 g, P < 0.001) white adipose tissue masses in the HFD-fed mice compared with no-supplement controls ( Fig. 1C). At 15 wk, half the mice in the HFD group were shifted to the HFD/META060 group,

and half the mice in the HFD/META060 group were shifted to the HFD-only group. Body weight was monitored weekly for 5 wk in these four treatment groups. Although the animals maintained on the HFD for the entirety of the experiment continued to gain weight, those shifted to the HFD/META060 group lost a

significant amount of weight during weeks 16 and 17, after which they began to gain weight again (Fig. 1D). A concomitant decrease in food intake was observed Doramapimod ic50 in the first 2 wk after switching diets, followed by a rebound to even higher levels than the food intake in mice in the HFD/META060 group that did not switch diets (data not shown), perhaps a reflection of an adjustment to the palatability differences between the distinct diets. To investigate how META060 protects against HFD-induced obesity, an independent 5-wk study was initiated with three treatment groups: HFD, HFD supplemented with META060 (100 mg ∙ kg−1 ∙ d−1), or HFD supplemented with rosiglitazone (1 mg ∙ selleck inhibitor kg−1 ∙ d−1). In the first 5 wk of the 14-wk intervention study, the average weight gained in the HFD group was 5.61 ± 0.7 g, whereas the Dynein mice supplemented with META060 gained 0.68 ± 0.3 g. In the 5-wk study, the average weight gained in the HFD group was 2.58 ± 0.4 g, and mice supplemented with META060 gained 0.54 ± 0.9 g (Fig. 2). Despite differences in the absolute weight gained, which was likely due to the difference in age of the mice at the start of each study, the META060 supplementation reproducibly decreased

the relative HFD-induced body weight gain in the two experiments. Whole-body substrate use was examined for approximately 36 h during week 4 of the dietary intervention. Four weeks of dietary intervention was chosen because, at this time point in the 14-wk study, body weight was still increasing and a new set point had not yet been reached. Although we did not directly compare the LFD group during the 5-wk study, we knew from published and experimental data that 5 wk of HFD feeding in mice results in an unaltered total energy expenditure (kilocalories per hour) but in changes RER, fat (FA), and CHO oxidation. Daytime RER was 0.84 ± 0.04 versus 0.94 ± 0.04, and night-time RER was 0.84 ± 0.03 versus 0.93 ± 0.04 for the HFD versus LFD group, respectively (P < 0.05). The daytime FA oxidation was 0.17 ± 0.05 versus 0.07 ± 0.04, and the night-time FA oxidation was 0.19 ± 0.05 versus 0.08 ± 0.06 for the HFD versus LFD group, respectively (P < 0.05).

We use only adult males, since preliminary studies using both mal

We use only adult males, since preliminary studies using both male and females, resulted buy E7080 in large variation in enzymes activities, probably due to physiological reproductive

variations in females. The insects were starved for 48 h and then fed ad libitum for 24 h with pupae of T. molitor L. Adults of P. nigrispinus were immobilized in cold and dissected in saline solution (0.1 M NaCl, 0.1 M KH2PO4, 0.1 M Na2HPO4, pH 7.2). Salivary glands and midguts were removed and stored at −80 °C until use. In some insects, the midgut was divided into three regions (anterior, middle and posterior). Samples of the salivary glands, whole midguts and midgut sections were homogenized in cold MilliQ water with the aid of a Potter–Elvehjem homogenizer. The homogenates were centrifuged at 16,000g for 30 min at 4 °C. The pellets and supernatants were stored at −20° C until use. For the enzymes assays pools of ten midguts were homogeneized in 500 μL of MiliQ water and 20 salivary glands in 100 μL in MiliQ water, whereas for enzymes purification a pool of 40 midguts were homogeneized in 1 mL of MiliQ water. No enzyme inactivation was detected on storage. The contents of the salivary glands and the midgut sections were dispersed in 5 μL ERK inhibitor manufacturer of MilliQ water and added to 5 μL of a 5-fold dilution of a universal pH indicator (E. Merck,

Darmstadt, pH 4–10). The resulting colored solutions were compared with suitable standard solutions diluted in 5 μL of MilliQ water. Protein content in extracts was determined according to Smith et al. (1985) as modified by Morton and Evans (1992), using bovine serum albumin (BSA) as a standard. Unless otherwise specified, hydrolase

assays were performed as follows. α-Amylase activity was measured by determining the appearance of reducing groups (Noelting and Bernfeld, 1948) in 50 mM citrate–phosphate buffer at pH 6.0 using 0.5% (w/v) starch as substrate. Absorbance was measured at 550 nm. Aminopeptidase assays were accomplished using 1 mM l-leucine p-nitroanilide (LpNA) as substrate in 50 mM citrate–phosphate buffer pH 6.0, according to Erlanger et al. (1961) and absorbance measured at 550 nm. α-Glucosidase selleck chemical activity was determined by following the release of p-nitrophenolate from 5 mM p-nitrophenyl-α-d-glucoside (pNPαGlu) in 50 mM citrate–phosphate buffer pH 6.0 and absorbance measured at 420 nm, as described in Terra et al. (1979). Serine protease (trypsin and chymotrypsin) assays were performed in 0.1 M Tris–HCl, pH 7.5 as follows. Activities were quantified by determining the methyl-coumarin fluorescence (excitation 360 nm and emission 460 nm) released from 1 mM carbobenzoxy-Phe-Arg-7-amino-4-methylcoumarin (Z-FR-MCA) in the case of trypsin and 1 mM succinyl-Ala-Ala-Pro-Phe-7-amino-4-methyl-coumarin (Suc-AAPF-MCA) in the case of chymotrypsin.

In the subsequent section, some of the versatility of the model i

In the subsequent section, some of the versatility of the model is illustrated based on empirical examples. First, however, it is important to explain how RBM differs from current management practices. This is important because RBM as a reform instrument acquires its identity in opposition to an established system. As the proposed RBM model has taken its starting

point in the ideas formulated by the European Commission, it is relevant to explore how it differs from a standard model of fisheries management in the CFP area. Fisheries management in the European Community is, as the Commission pointed out in the Green Paper, generally centralized and “top down”. While main policies and regulations Z-VAD-FMK mw are being decided in common, implementation and monitoring is generally left to individual member states. In principle the main biological objective pursued is to keep stocks above MSY levels [27]. Annual management decisions focus on TAC levels for single stocks and are based on stock assessment and advice performed within ICES [28] and [29]. The stock assessments High Content Screening are based on data collected by member states or obtained through international data collection programmes. Most stocks are managed by way of a combination of TACs, gear and area restrictions, effort limits, and minimum

landing sizes. Fishing activities are subjected to a number of regulations that specify how much, where, how, what, when and with which gear one may fish. These brief characteristics are intended to capture, in a simplified way, the standard approach to fisheries management within the CFP, in order to compare

it to the described RBM model. The CFP model has structural elements in common with the RBM model: the management process is oriented towards achieving specific objectives, which are related to relevant indicators (MSY related reference points defined in relation to F or SSB) and performance regarding those objectives is assessed regularly (annual stock assessments) as a basis for decision making. Thymidylate synthase But the two others defining features of the RBM model are absent as the burden of evidence generally remains placed with the management authority [20] and [21] and as resource users have little or no flexibility regarding management measures and regulations. When the Commission in 2009 proposed RBM as an approach suitable for reforming the CFP it could draw on a limited number of practical cases, both within and outside the EU, where such an approach had been deployed. Some of these cases had been explicitly developed according to a notion of RBM [18] and [30]. Other cases bear strong structural similarity to the model of RBM proposed here, despite being identified by different labels [23], [26], [31], [32], [33], [34], [35], [36], [37], [38] and [39].

, 2010 and Mata et al , 2010)

, 2010 and Mata et al., 2010). Selleck GDC-0980 The authors suggest combining the macro-algae and using large amounts of raw materials to obtain a homogenous high lipid content, and accordingly these seaweeds could be exploited as a source of biodiesel. The present study showed that marine algae subjected to seasonal variations exhibit different concentrations of total, saturated and unsaturated fatty acids, with a characteristic profile for each. This is expected for distant systematic relationships between these algae. Both U. linza and P. pavonica had

the highest fatty acid percentages throughout the entire year compared to J. rubens. Palmitic acid (C16:0) was at relatively high concentrations. For U. linza and P. pavonica, palmitic acid comprised approximately 70%. For J. rubens, it comprised approximately 30% of the total saturated fatty acids for the studied seasons. This is a distinctive characteristic because palmitic acid (C16:0) is the primary saturated fatty acid in several seaweeds ( Bemelmans

et al., 2002, Denis et al., 2010, El-Shoubaky et al., 2008, Khotimchenko, 1991 and Matanjun et al., 2009). Simultaneously, docosahexaenoic acid (C22:6) presented with higher concentrations of unsaturated fatty acids in approximately 50% of these algae during the different seasons. However, for U. linza and P. pavonica, it was approximately 25% in autumn and summer, respectively. Gosch et al. Dasatinib cost (2012) reported that this essential

polyunsaturated fatty acid is most common in the green seaweeds but is less in the brown and red seaweeds. By contrast, Khairy and El-Shafay (2013) found that it was a primary component in several macro-algae. Oxymatrine Belarbi et al. (2000) and Chisti (2007) reported that algal oils differ from vegetable oils because they are relatively rich in polyunsaturated fatty acids with four or more double bonds, such as docosahexaenoic acid, which commonly occurs in algal oils. For the ratios of saturated to unsaturated fatty acids in this study, P. pavonica exhibited the highest ratios (3.23, 3.37 and 4.05), followed by U. linza (2.55, 2.56 and 3.90), whereas J. rubens displayed relatively low ratios (0.85, 0.76 and 1.09) during the summer, autumn and spring, respectively. The principal component analysis shown in Fig. 1a–c separates these seaweeds based on their total, saturated and unsaturated fatty acids into two groups, with the brown and green seaweeds grouped together and the red seaweed grouped out. However, quantification of the fatty acid components and varying degrees of saturation were significant factors in determining the suitability of these oils as biodiesel feedstock. Ramos et al. (2009) reported that monounsaturated, polyunsaturated and saturated methyl esters predict the critical parameters of the European standard for any biodiesel composition.

As a consequence a person’s phenotype is considered dynamic and r

As a consequence a person’s phenotype is considered dynamic and resilience becomes a key parameter. Resilience is best evaluated during a system response, so challenge-tests will become more common in metabolomics research

[9•]. A classic example is the oral glucose tolerance test, but also high fat challenges, exercise, stress or mixed diets are used. Phenotype dynamics will differ between individuals, and concepts as homeostasis and allostasis can be considered (Figure 1). However, a precise (dynamic) description of the clinical phenotype Selleckchem PI3K inhibitor is currently missing, which is of utmost importance to guide the discovery of diagnostic and mechanistic biochemical biomarkers. Another challenge is that mostly body fluids such as blood and urine are available, but most studied biochemical networks

are at the cellular level and not at the systems regulatory level. Therefore, we need to address cross-compartment communication and system organization more than only the pathways within cells. We expect that with the proper phenotyping/genotyping, metabolomics will play an important role in systems diagnosis, with an emphasis on following the changes over time of an individual [15], and on find more a somewhat longer term on integrated interventions and Tau-protein kinase personalized wellness (Figure 2). The analytical strategy needed to be developed for achieving this is discussed below. In metabolomics the general tendency is to analyze as many low-molecular weight compounds (less than 2000 Da) as possible in a given biological sample at a certain point in time with the aim to obtain maximal biochemical information. The most recent version of the Human Metabolome Database contains 40 335 metabolite entries, of which a major part consists of lipids [16]. This number does

not only include endogenous metabolites but also exogenous compounds originating from nutrients, microbiota, drugs and other sources. However, it is our opinion that this number is still an underestimation of the actual size of the human metabolome. Despite the fact that advanced analytical techniques like nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) hyphenated to gas chromatography (GC), liquid chromatography (LC) and/or capillary electrophoresis (CE) have become well-established tools for metabolomics studies [17, 18••, 19, 20 and 21], they still can only capture a part of the human metabolome and, therefore, provide inherently biased results. We expect that new developments or further refinements of analytical technologies, especially with regards to sensitivity, will significantly increase the coverage of metabolites.

A QFT-G test was performed at the time of this visit; testing

A QFT-G test was performed at the time of this visit; testing NVP-BKM120 mw was performed at a single large commercial laboratory. The QFT-G test results were interpreted according to the manufacturer’s instructions [8]. Active TB disease was excluded using symptom review, physical examination, chest radiography, and, if necessary, sputum collection for acid-fast bacilli smear microscopy and mycobacterial culture. Clinic providers reviewed

the medical records and extracted data including age, gender, country of origin, length of residence in the United States, TST reaction size measured in millimeters of induration, chest radiograph findings, and risk factors for the development of TB disease. A high-incidence country was defined as a country with an incidence of ≥20 cases of acid-fast smear-positive pulmonary TB per Erastin 100,000 persons [9]. A step-wise logistic regression was used to determine the odds ratios (ORs) for demographic and clinical factors that were predictive of a positive QFT-G result. Age and TST induration were modeled as continuous variables. A P value of <0.05 was considered significant. A review of the study determined that it entailed an assessment of routine public health practice

and was not considered human subjects research. The Institutional Review Board of St. Francis Hospital and Medical Center (Hartford, CT) approved this retrospective cohort study. A total of 100 BCG-vaccinated adults who were referred to the pulmonary clinic because of a positive TST result were included in the study. The median patient age was 34 years, nearly half (46%) were male, and the study participants had been in the United States for a median duration of 4.5 years (range 0–44 years). The participants were from 42 different countries representing the Americas (47%), Europe (20%), Africa (18%), Southeast Asia (6%), the western Pacific (6%), and the eastern Mediterranean (3%). Their birth countries had a median TB incidence of 37 cases per 100,000 population (range 2–312 cases); 57% were from countries

with a high incidence of TB. The median TST induration was 15 mm. Among the 100 persons with positive TST results, 30 (30%) also had a positive QFT-G RG7420 supplier result (Fig. 1). One QFT-G result was indeterminate, but a repeat test was negative. Twenty-six (46%) of the 57 adults from high-incidence countries were QFT-G positive (Table 1); in contrast, 4 of 43 adults (9%) from low-incidence countries were positive (OR = 8.2; 95% confidence interval (CI), 2.4–31.1). None had active TB disease. A logistic regression was used to compare tuberculin reactivity. Persons with a TST induration ≥ 16 mm had a more than six fold greater likelihood of having a positive QFT-G result than persons with a smaller TST induration (Table 2). The combination of being from a high-incidence country and having a TST induration ≥ 16 mm also strongly predicted QFT-G positivity (Table 2).

Net samples were preserved immediately after collection in a 4% b

Net samples were preserved immediately after collection in a 4% borax-buffered formaldehyde-seawater solution. A total of 245 samples from 24 stations were analysed. The crustacean zooplankton was identified in the laboratory under a stereoscopic microscope. Representatives of taxa belonging to Copepoda, Cladocera and Cirripedia, and the developmental stages (nauplii, copepodites I–V, mature males

and females) were identified. The epizoic and parasitic protozoans on crustaceans were also identified, and the degree of infestation and the location of protozoans on various body parts were investigated. Three different ranges of infestation Ibrutinib manufacturer were arbitrarily distinguished: up to 13, from 13 to 12, and more than 12 the body surface. Analysis of the plankton material revealed the presence of Copepoda (Calanoida: Acartia longiremis  , Acartia bifilosa  , Acartia

tonsa  , Temora longicornis  , find more Centropages hamatus  , Eurytemora   sp. Pseudocalanus   sp. and representatives of Harpacticoida – typical zoobenthic copepods), Cladocera (Bosmina   sp. Evadne nordmanii  , Pleopsis polyphemoides  , Podon   sp. and freshwater organisms) and Cirripedia larvae (Balanus improvisus  ). The parasites attached to the crustacean bodies were classified as the genus Ellobiopsis   (Myzozoa, Ellobiopsida) ( Figures 1A–C). The epizoic protozoans observed on crustaceans of the Gulf of Gdańsk belong to Peritricha (Vorticellidae). Dapagliflozin Ciliated epibionts were divided into two categories: Peritricha type I – individual organisms or tufts of organisms (like the genus Vorticella  ) and Peritricha type II – clearly branched colonies (like the genus

Zoothamnium  ) ( Figure 1D–F). Such discrimination was introduced owing to the deformation of the body of organisms observed in the preserved material. Epibionts and parasites were noted on various crustacean taxa.Calanoida (Copepoda) overgrown with ciliated Protozoa (Peritricha types I and II) were observed, as were body deformations related to the presence of the parasite Ellobiopsis   ( Figure 1A, D, E) ( Table 2 and Table 3). These organisms were found at all research stations and in all research periods, and constituted from 4% (2006) to 16% (1998) of all Copepoda ( Table 2). The prevalence of Peritricha type II was from 0.8% to 13% of the total population of each taxa (max. infestation in Acartia   spp. in 1998), and that of Ellobiopsis   was 2–11% (max. infestation in Temora longicornis   in 1999). Representatives of Peritricha type I (cf. Vorticella  ) were less frequently noted on copepods – 0.1–9.2% of the population were infested ( Table 2). The dominant taxa of Copepoda of the Gulf of Gdańsk were the most commonly attacked ( Table 3) – Acartia   spp. (up to 54% of all infested calanoids), Temora longicornis   (26–49% of all infested calanoids) and Centropages hamatus   (10.5–13% of all infested calanoids).

Mais de 80 mutações amiloidogénicas no gene da transterritina já

Mais de 80 mutações amiloidogénicas no gene da transterritina já foram identificadas, mas a mais comum é a mutação TTR met 30, em que ocorre a substituição da valina por metionina na posição 301. A história natural da doença caracteriza-se por phosphatase inhibitor library uma neuropatia sensitivo-motora e autonómica, rapidamente progressiva, com evolução

para a caquexia e morte em 10 a 20 anos após o início dos sintomas1 and 2. Portugal representa o maior foco mundial desta mutação específica, com mais de 500 famílias afetadas1 and 2. Está amplamente descrita na literatura a penetrância incompleta, a variabilidade de idade do início dos sintomas e diversidade de formas

de apresentação clínica desta patologia. O início da sintomatologia ocorre antes dos 40 anos em 80% dos casos com manifestações sensitivas e autonómicas1 and 2. O envolvimento motor surge mais tarde na evolução da doença. O caso clínico apresentado é ilustrativo da complexidade semiológica com que um doente com PAF se pode apresentar. Do estudo do caso clínico apresentado destacam-se 2 aspetos fundamentais. Em primeiro lugar a forma de apresentação e o facto de se desconhecer a história familiar paterna convenientemente. Em segundo lugar, o facto de a biópsia retal para pesquisa da substância amiloide ter sido negativa. Os órgãos primordialmente biopsados para fins diagnósticos têm sido classicamente o reto ou a gordura subcutânea, RG7204 cost com especificidade entre 75-94%3. As manifestações gastrointestinais constituíram as manifestações iniciais da doença. Na fase mais avançada, a diarreia tornou-se incoercível e associada GNE-0877 a incontinência fecal, o que pode surgir em mais de 80% dos doentes nos estádios ii e iii4. Múltiplos mecanismos foram descritos como causa da diarreia, desde a infiltração das vilosidades intestinais pela substância amiloide causando uma

alteração tipo «sprue-like», bem como a alteração autonómica pela invasão amiloide dos plexos Auerbach e Meissner e gânglios autonómicos induzindo uma aceleração do trânsito intestinal com subsequente má absorção dos sais intestinais3. Também está descrito o contributo da proliferação bacteriana como consequência da má absorção biliar e/ou alterações da motilidade do intestino delgado, podendo ambos levar à esteatorreia3. Para além destes fatores, a diarreia pode ser secundária a uma insuficiência pancreática, por infiltração arterial de substância amiloide, induzindo um processo de isquemia crónica pancreática3. Esta grande variabilidade etiológica explica a resposta individual dos diferentes tratamentos conservadores.