Policultivo de amaranto con leguminosas, una alternativa de manejo agroecológico de malezas para agricultores familiares de la provincia de Buenos Aires

La necesidad de un sistema agropecuario más sustentable, ecológicamente adecuado, y socialmente aceptable, que provea una alimentación variada y de calidad, es hoy una realidad en la Provincia de Buenos Aires. El cultivo del amaranto (Amaranthus sp.), alimento altamente nutritivo y con gran potencial para adaptarse a las condiciones agroecológicas de la provincia de Buenos Aires, es una posibilidad. Una de sus dificultades es el control de malezas sin uso de agroquímicos. El objetivo de este trabajo es evaluar, desde un enfoque agroecológico, el uso de policultivos con leguminosas (Vicia villosa y Trifolium pratense), como alternativa a dicho problema. Los resultados de esta experiencia muestran que el amaranto y las leguminosas, al ocupar nichos ecológicos distintos, no presentan fuerte competencia entre sí y, por lo tanto, la siembra de Vicia villosa con amaranto aparece como una estrategia adecuada para el manejo ecológico de malezas para agricultores familiares de la provincia de Buenos Aires.The need of agricultural system more sustainable, ecologically suitable and aceptable socially, that provides varied and quality alimentation, is now the reality of Province of Buenos Aires. The crop amaranth incorporation (Amaranthus sp.), very nutritious food and with great potential to suit the agro-ecological conditions of the province of Buenos Aires, is a posibility. one of the difficulties is to control weeds without using chemicals. The aim of this study is to evaluate , from an agro-ecological approach , using intercropping with legumes (Vicia villosa and Trifolium pratense), as an alternative to this problem.The results from that experience show that the amaranth and the legumes, occupy differents niches, no significant competition between them, so, the planting of vicia villosa and amaranth appear like suitable strategy to do an ecological management of weeds for family farmers from Province of Buenos Aires.Eje: A1: Sistemas de producción de base agroecológic

Policultivo de amaranto con leguminosas, una alternativa de manejo agroecológico de malezas para agricultores familiares de la provincia de Buenos Aires

La necesidad de un sistema agropecuario más sustentable, ecológicamente adecuado, y socialmente aceptable, que provea una alimentación variada y de calidad, es hoy una realidad en la Provincia de Buenos Aires. El cultivo del amaranto (Amaranthus sp.), alimento altamente nutritivo y con gran potencial para adaptarse a las condiciones agroecológicas de la provincia de Buenos Aires, es una posibilidad. Una de sus dificultades es el control de malezas sin uso de agroquímicos. El objetivo de este trabajo es evaluar, desde un enfoque agroecológico, el uso de policultivos con leguminosas (Vicia villosa y Trifolium pratense), como alternativa a dicho problema. Los resultados de esta experiencia muestran que el amaranto y las leguminosas, al ocupar nichos ecológicos distintos, no presentan fuerte competencia entre sí y, por lo tanto, la siembra de Vicia villosa con amaranto aparece como una estrategia adecuada para el manejo ecológico de malezas para agricultores familiares de la provincia de Buenos Aires.The need of agricultural system more sustainable, ecologically suitable and aceptable socially, that provides varied and quality alimentation, is now the reality of Province of Buenos Aires. The crop amaranth incorporation (Amaranthus sp.), very nutritious food and with great potential to suit the agro-ecological conditions of the province of Buenos Aires, is a posibility. one of the difficulties is to control weeds without using chemicals. The aim of this study is to evaluate , from an agro-ecological approach , using intercropping with legumes (Vicia villosa and Trifolium pratense), as an alternative to this problem.The results from that experience show that the amaranth and the legumes, occupy differents niches, no significant competition between them, so, the planting of vicia villosa and amaranth appear like suitable strategy to do an ecological management of weeds for family farmers from Province of Buenos Aires.Eje: A1: Sistemas de producción de base agroecológic

Policultivo de amaranto con leguminosas, una alternativa de manejo agroecológico de malezas para agricultores familiares de la provincia de Buenos Aires

La necesidad de un sistema agropecuario más sustentable, ecológicamente adecuado, y socialmente aceptable, que provea una alimentación variada y de calidad, es hoy una realidad en la Provincia de Buenos Aires. El cultivo del amaranto (Amaranthus sp.), alimento altamente nutritivo y con gran potencial para adaptarse a las condiciones agroecológicas de la provincia de Buenos Aires, es una posibilidad. Una de sus dificultades es el control de malezas sin uso de agroquímicos. El objetivo de este trabajo es evaluar, desde un enfoque agroecológico, el uso de policultivos con leguminosas (Vicia villosa y Trifolium pratense), como alternativa a dicho problema. Los resultados de esta experiencia muestran que el amaranto y las leguminosas, al ocupar nichos ecológicos distintos, no presentan fuerte competencia entre sí y, por lo tanto, la siembra de Vicia villosa con amaranto aparece como una estrategia adecuada para el manejo ecológico de malezas para agricultores familiares de la provincia de Buenos Aires.Eje: A1: Sistemas de producción de base agroecológicaFacultad de Ciencias Agrarias y Forestale

Policultivo de amaranto con leguminosas, una alternativa de manejo agroecológico de malezas para agricultores familiares de la provincia de Buenos Aires

La necesidad de un sistema agropecuario más sustentable, ecológicamente adecuado, y socialmente aceptable, que provea una alimentación variada y de calidad, es hoy una realidad en la Provincia de Buenos Aires. El cultivo del amaranto (Amaranthus sp.), alimento altamente nutritivo y con gran potencial para adaptarse a las condiciones agroecológicas de la provincia de Buenos Aires, es una posibilidad. Una de sus dificultades es el control de malezas sin uso de agroquímicos. El objetivo de este trabajo es evaluar, desde un enfoque agroecológico, el uso de policultivos con leguminosas (Vicia villosa y Trifolium pratense), como alternativa a dicho problema. Los resultados de esta experiencia muestran que el amaranto y las leguminosas, al ocupar nichos ecológicos distintos, no presentan fuerte competencia entre sí y, por lo tanto, la siembra de Vicia villosa con amaranto aparece como una estrategia adecuada para el manejo ecológico de malezas para agricultores familiares de la provincia de Buenos Aires.Eje: A1: Sistemas de producción de base agroecológicaFacultad de Ciencias Agrarias y Forestale

Conversión de prueba cutánea de derivado proteico purificado durante el tratamiento con anti-TNF-α

Introducción: los anti-TNF-α se asocian con mayor riesgo de desarrollar tuberculosis (TB). La prueba del derivado proteico purificado (purified protein derivative, PPD) se emplea para diagnosticar infección de tuberculosis latente (ITL). Se recomienda el cribado para TB previo al inicio de terapia anti-TNF-α y el seguimiento para evaluar la posible conversión de la PPD durante el tratamiento. El tratamiento de la ITL puede reducir el riesgo de desarrollar enfermedad activa en un 90%. Objetivos: actualmente los resultados de conversión de la PPD y su interpretación durante el tratamiento anti-TNF-α son variables, por tal motivo nos propusimos conocer la frecuencia de conversión de la PPD en este grupo de pacientes de nuestro medio

Translational research in the role of intragastric pressure changes and gastric accommodation in the pathogenesis of impaired food tolerance

Functional dyspepsia (FD) is a highly prevalent gastrointestinal (GI) disorder defined as “the presence of epigastric symptoms in the absence of any underlying organic or metabolic disease that is likely to explain the symptoms”. Based mainly on expert opinion, the Rome III consensus, proposed to subdivide FD into Postprandial distress syndrome (PDS), the major group, characterized by frequent postprandial fullness and/or early satiation, and epigastric pain syndrome (EPS), characterized by frequent epigastric pain and/or epigastric burning. In clinic samples, overlap of PDS and EPS is found in up to 50% of the patients, having a significant negative impact on the usefulness of the subdivision. The current therapeutic approach to this condition is based on the reduction of GI symptoms by means of diet, and especially medication such as acid suppressive and prokinetic drugs. Nevertheless, the efficacy of these therapies is limited and the development of novel options is hampered on the one hand by incorrect patient selection and inappropriate use of endpoints or endpoint questionnaires, and on the other hand by the heterogeneity and multifactorial nature of this condition. One of the most relevant proposed underlying mechanisms is impaired gastric accommodation (GA). GA is measured by means of the gastric barostat which is also considered the gold standard. However, this procedure is very invasive, difficult to tolerate and is likely to disturb normal physiological mechanisms. Hence, there is clearly a lack of a suitable measurement technique to optimally study and completely understand GA. Taking into account the gaps in the state of the art, this thesis comprises different objectives. The first objective was to optimise the assessment of the symptom pattern in FD and to explore its correlation with the underlying pathophysiology. Adequate symptom assessment is crucial for improving FD management and patient selection for clinical trials. On the one hand, this was done by exploring an approach to improve the subdivision and classification of FD into EPS and PDS subgroups and by studying the link between FD symptoms and the prevalence of several underlying pathophysiological mechanisms (chapter 2). On the other hand, we aimed to develop and validate an endpoint questionnaire for PDS based on the US FDA guidance (chapter 3). The second objective was to validate and apply a new technique to assess GA in response to food intake, the intragastric pressure (IGP) measurement by means of high resolution manometry. This validation includes comparing physiological measurements in FD and healthy controls (chapter 4), as well as assessment of pharmacological influences in healthy subjects (chapter 5) to explore the physiological control mechanisms of IGP and their role in generating dyspeptic symptoms. Finally, we aimed at expanding the therapeutic abilities in FD by conducting therapeutic intervention studies (chapter 5&6). Chapter 2: FD patients fulfilling the ROME III criteria were subdivided into “pure” PDS, “pure” EPS and overlapping EPS-PDS subgroups. In addition to the classical Rome III questionnaire, the postprandial nature of a number of non-PDS symptoms was also assessed by a number of questions. 2.1: No differences in the prevalence of pathophysiological measured by the gastric barostat (impaired gastric accommodation, increased gastric sensitivity to distention) and by the gastric empting test were observed in the PDS, EPS and overlap subgroups as defined by the Rome III criteria. Despite the fact that there were no relations found between pathophysiology and symptoms, it is known that the meal is an important factor originating or aggravating symptoms in FD patients. 2.2: Compared to “pure” EPS patients, the overlapping EPS-PDS patients were characterized by a higher postprandial occurrence of non-PDS symptoms such as pain or nausea. Taking into account the prevalence of these symptoms in the overlap subgroup, patients were reclassified in the “new PDS” group. In this “adapted” subdivision the overlap PDS-EPS subgroup was shown to be reduced and the “new” PDS subgroup was characterized by meal-related PDS symptoms as well as postprandial EPS symptoms. 2.3: Similar results were achieved in an experimental set-up where the frequency of symptoms (Rome III) and additional meal-related questions were compared to severity scores reported after the ingestion of a standardized meal. Here, it was shown that PDS and the overlap subgroup patients suffer similarly from symptoms after the meal, while the patients in the EPS subgroup, show a completely different symptom pattern. Chapter 3: The choice to start with the PDS subgroup for the development of a new patient reported outcome (PRO) questionnaire, was driven by the larger proportion of PDS patients compared to EPS patients and by the availability of a large number of prokinetic drugs that need to be studied in this patient group. 3.1: By means of focus group sessions and cognitive interviews, relevant PDS symptoms were identified and question items were developed and expressed as questions as a pilot PRO instrument with a 5 point-severity-scale. 3.2: In order to assess its validity, reliability and responsiveness, a double blind, multicentre randomized, placebo-controlled parallel-group study with itopride in 60 PDS patients was conducted. During 2 week eligibility screening period and 8 weeks of treatment patients assessed the severity of their symptoms using the pilot LPDS questionnaire as daily diary. In addition, patients also filled out the Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM), the Nepean Dyspepsia Index (NDI), overall treatment evaluation (OTE) and overall symptom severity (OSS) questionnaires. Construct validity was evaluated by known-group analyses and by correlating (changes in) LPDS scores with (changes in) anchors like OTE, OSS, early satiation/postprandial fullness domain of PAGI-SYM and eat/drink domain of NDI. The minimum Clinically Important Difference (MCID) was determined from clinically relevant threshold changes in anchor questionnaires. 3.3: Furthermore, after expansion of the patient group to 99 participants, content validity, consistency, reliability was confirmed, not only in the “pure” PDS group but also in PDS patients with overlapping non-predominant EPS. Chapter 4: The measurement of intragastric pressure by means of high-resolution manometry during nutrient intake has recently been proposed as a potential minimally invasive alternative to assess GA. 4.1: IGP measurements showed that FD patients have lower nutrient tolerance and a smaller IGP drop during the intragastric infusion of the liquid meal compared to controls. Forty-five per cent of FD patients tolerated a maximum nutrient volume below the 10th percentile observed in controls. A moderate but significant correlation was seen between the nadir IGP and the amount of ingested meal, suggesting that subjects with more severe decreased nutrient tolerance are more likely to have a smaller drop in IGP during nutrient drink infusion, and by extension, poor gastric accommodation. Higher scores of pain, nausea and intestinal cramps during the intragastric infusion of the nutrient drink were also associated with a higher nadir IGP, indicating that a reduced drop in IGP is associated with higher postprandial dyspeptic symptom load. 4.2: Assessment of intragastric volume distribution by means of scintigraphy images during nutrient drink infusion, showed a clear relationship to the filling of the proximal stomach and a drop in IGP in the proximal stomach with satiation scores, rather than the filling and the IGP drop of the distal stomach. This indicates the importance of the proximal stomach as a reservoir and as determinant of satiation during ingestion of a meal. Overall, these data indicate that intragastric pressure measurement during a nutrient drink test has the potential to become a clinically relevant assessment of (patho)physiological factors and symptom generation. Chapter 5: The effect of novel motility-modifying agents on gastric motility and sensitivity were studied by means of gastric barostat and IGP measurements. 5.1: Sildenafil citrate is a potent specific PDE5 inhibitor which enhances NO diffusion in smooth muscles leading to muscle relaxation. Previous results with the barostat showed that sildenafil may enhance GA. On the other hand, its use in the treatment of erectile dysfunction is associated with dyspeptic symptoms as the most frequent adverse event. IGP measurement after an acute intake of sildenafil (PO, 50 mg), showed increased intragastric pressure, decreased nutrient tolerance, decreased gastric emptying rate and increased epigastric symptoms in healthy subjects. All are potentially relevant to dyspeptic symptom generation after use of this drug. 5.2: Prucalopride, a selective serotonin (5-HT4) agonist, is indicated for the treatment of chronic constipation, but was also shown to improve gastric emptying. Barostat measurements after an acute intake of prucalopride (PO, 2 mg), showed no significant effect on gastric accommodation but a tendency to increase gastric sensitivity. IGP measurements showed increased antral contractile activity associated to abdominal cramps. No effect was observed on IGP drop or nutrient tolerance. During the barostat study only, a large proportion of the subjects terminated earlier the study due to bothersome occurrence of nausea and the urge to vomit. This might be attributable to prucalopride-induced increased sensitivity to gastric distention and antral contractions alongside the intragastric barostat balloon. 5.3: Mirtazapine is a tricyclic antidepressant that has shown to improve symptoms, nutrient tolerance and body weight in FD patients with weight loss. After 3 weeks of treatment (PO, 15 mg) in healthy volunteers, IGP measurements showed a decrease of IGP drop. However, no decreased nutrient tolerance was observed, possibly because of central effects of the drug. During the barostat test, only a tendency to decreased gastric sensitivity was observed. The findings suggest that mirtazapine acts mainly centrally in improving FD symptoms and nutrient tolerance. Chapter 6: The efficacy of prucalopride was studied in patients with idiopathic gastroparesis after a double-blind, randomized, placebo-controlled cross-over study. After 4 weeks of treatment prucalopride significantly enhanced gastric half emptying time compared to placebo and to baseline and also significantly improved upper abdominal symptoms such as nausea, fullness/satiety, bloating and reflux and quality of life compared to placebo.Acknowledgements I List of abbreviations IV Table of contents VI Chapter 1 General introduction, hypotheses and aims 1 1.1. The stomach 2 1.2. Brain-gut interaction 2 1.3. The digestion 3 1.4. Functional dyspepsia 5 1.5. Objectives of the research 14 Chapter 2 Pathophysiology and validity of functional dyspepsia subgroups 15 2.1. Pathophysiological abnormalities in functional dyspepsia subgroups according to the Rome III criteria 16 2.1.1. Introduction 16 2.1.2. Materials and Methods 16 2.1.3. Results 19 2.1.4. Discussion 22 2.2. Rome III Functional dyspepsia subdivision in PDS and EPS: recognizing postprandial symptoms reduces overlap. 26 2.2.1. Introduction 26 2.2.2. Materials and Methods 27 2.2.3. Results 28 2.2.4. Discussion 29 2.3. Analysis of postprandial symptom patterns allows better separation of subgroups of functional dyspepsia patients 31 2.3.1. Introduction 31 2.3.2. Materials and Methods 31 2.3.3. Results 33 2.3.4. Discussion 42 Chapter 3 Development and validation of PRO questionnaires 45 3.1. Rome III Functional dyspepsia symptoms classification: severity vs. frequency 46 3.1.1. Introduction 46 3.1.2. Materials and methods 46 3.1.3. Results 47 3.1.4. Discussion 51 3.2. Functional Dyspepsia: outcome of focus groups for the development of a questionnaire for symptom assessment in patients suffering from Postprandial Distress Syndrome (PDS) 53 3.2.1. Introduction 53 3.2.2. Materials and Methods 54 3.2.3. Results 57 3.2.4. Discussion 60 3.3. Validation of the Leuven Postprandial Distress Scale (LPDS), a questionnaire for symptom assessment in Functional Dyspepsia - Postprandial Distress Syndrome 62 3.3.1. Introduction 62 3.3.2. Materials and Methods 63 3.3.3. Results 69 3.3.4. Discussion 74 3.4. Validity of Leuven Postprandial Distress Scale (LPDS) in the PDS-EPS subgroup overlap 76 3.4.1. Introduction 76 3.4.2. Materials and Methods 76 3.4.3. Results 80 3.4.4. Discussion 84 Chapter 4 The assessment of intragastric pressure in functional dyspepsia patients and healthy subjects. 85 4.1. Intragastric pressure measurement in functional dyspepsia and healthy subjects 86 4.1.1. Introduction 86 4.1.2. Materials and Methods 87 4.1.3. Results 88 4.1.4. Discussion 92 4.2. Impaired gastric distribution of a meal is associated with impaired meal-induced intragastric pressure (IGP) drop and early satiation in functional dyspepsia (FD). 94 4.2.1. Introduction 94 4.2.2. Materials and Methods 94 4.2.3. Results 97 4.2.4. Discussion 104 Chapter 5 Evaluation of novel therapeutic pathways with the gastric barostat and intragastric pressure measurement. 107 5.1. Sildenafil: The effect of sildenafil citrate on gastric motility and satiation in healthy volunteers. 108 5.1.1. Introduction 108 5.1.2. Materials and Methods 108 5.1.3. Results 110 5.1.4. Discussion 112 5.2. The effect of prucalopride in gastric sensorimotor function and satiation in healthy volunteers 114 5.2.1. Introduction 114 5.2.2. Materials and Methods 114 5.2.3. Results 118 5.2.4. Discussion 126 5.3 The effect of mirtazapine on gastric accommodation and gastric sensitivity in healthy volunteers 129 5.3.1. Introduction 129 5.3.2. Materials and Methods 129 5.2.3. Results 132 5.3.4. Discussion 139 Chapter 6 The evaluation of novel therapeutic options in FD patients 141 6.1. Prucalopride in gastroparesis: a randomized placebo-controlled cross-over study 142 6.1.1. Introduction 142 6.1.2. Materials and methods 142 6.1.3. Results 145 6.1.4. Discussion 148 Chapter 7 General discussion and future prospects 151 Reference list 157 Abstract 177 Summary 178 Sammenvatting 181 Curriculum Vitae 185nrpages: 196status: publishe

Opioids in Gastroparesis: Bystander or Cause?

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Joint Hypermobility Syndrome in Patients With Functional Dyspepsia.

INTRODUCTION: The pathophysiology underlying functional dyspepsia (FD) is multifactorial and focuses on gastric sensorimotor dysfunction. Recent studies demonstrated that joint hypermobility syndrome (JHS) is strongly associated with unexplained dyspeptic symptoms in patients attending gastrointestinal clinics. We aimed to study the relationship between symptoms, gastric sensorimotor function, and JHS in FD patients. METHODS: Tertiary care FD patients who underwent a gastric barostat study and a gastric emptying breath test with 13C-octanoic acid were recruited for assessment of JHS. The presence of JHS was evaluated by a 2-phase interview and clinical examination that included major and minor criteria of the Brighton classification. RESULTS: A total of 62 FD patients (68% women, age 44 ± 1.8 years, and body mass index: 21.7 ± 0.7 kg/m) accepted to participate in the study. JHS was diagnosed in 55% of FD patients. Assessed symptom profiles during the visit did not differ between the groups. Delayed gastric emptying was not significantly more common in JHS group compared with non-JHS group (JHS group 32% vs non-JHS group 16%, P = 0.31). Prevalence of hypersensitivity to distention (JHS group 24% vs non-JHS group 29%, P = 0.76) and impaired gastric accommodation (JHS group 38% vs non-JHS group 42%, P = 0.79) was similar in patients with or without JHS. No correlations were found between the Beighton hypermobility score and gastric compliance (r = 0.09). DISCUSSION: A large subset of this study cohort of tertiary care FD patients has coexisting JHS. We did not identify any specific differences in gastric sensorimotor function between patients with and without JHS. Further prospective research will be required to elucidate the relationship between JHS, a multisystemic disorder with widespread manifestations, and FD symptoms.status: publishe

The Unfulfilled Promise of Prokinetics for Functional Dyspepsia/Postprandial Distress Syndrome

Functional dyspepsia (FD) is subdivided into epigastric pain syndrome and postprandial distress syndrome according to the Rome IV consensus. Based on the assumption that disordered gastric motility is a key pathophysiologic factor in postprandial distress syndrome, prokinetic agents are often proposed as the treatment of choice for this subgroup. Although a meta-analysis suggests that prokinetic agents may be efficacious and safe in FD, there is a lack of widely available agents of proven efficacy. This review analyzes some of the difficulties and challenges in establishing therapeutic efficacy of prokinetic drugs in FD.status: publishe

Postprandial distress syndrome: stratification and management

INTRODUCTION: Functional dyspepsia (FD), defined by the Rome consensus as the presence of functional symptoms originating from the gastroduodenum, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. We used a literature search for a narrative review on the current state of knowledge regarding PDS. Areas covered: Epidemiological studies support PDS as a separate entity and the biggest FD subgroup. The pathophysiology of PDS is heterogeneous, and disorders of gastric sensorimotor function as well as low grade duodenal inflammation have been implicated. Although prokinetic agents may provide the most pathophysiology-oriented treatment option, there is a paucity of suitable agents, and proton pump inhibitors are the traditional first-line therapy. Other options include agents that enhance gastric accommodation, such as acotiamide and 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches. Expert commentary: PDS is highly prevalent, with probably heterogeneous underlying pathophysiology. Motility modifying agents and neuromodulators are the cornerstone of PDS therapy, but there is a need for high quality studies of new therapeutic approaches.status: publishe