Aminoácidos + análogos associados à dieta muito restritiva em proteínas para o tratamento de pacientes adultos com doença renal crônica em estágios 4 ou 5 pré-dialítico / Amino acids + analogues associated with a very restrictive protein diet for the treatment of adult patients with chronic kidney disease in stages 4 or 5 pre-dialysis

INTRODUÇÃO: A doença renal crônica (DRC) é atualmente entendida como um problema de saúde pública, devido a sua prevalência crescente, morbimortalidade elevada e altos custos demandados para a manutenção dos pacientes renais crônicos dialíticos nas diversas modalidades de terapia renal substitutiva (TRS) existentes. Um dos objetivos do tratamento de pacientes portadores de DRC é a prevenção da progressão da doença e de suas complicações. Dietas restritas em proteína são medidas que podem minimizar a esclerose glomerular, portanto retardar a progressão da DRC e, atualmente, consiste na única alternativa não farmacológica existente no sistema único de saúde de saúde (SUS). PERGUNTA DE PESQUISA: O uso de aminoácidos e cetoanálogos (CA) associados à dieta muito restrita em proteínas (VLPD) é seguro e eficaz em pacientes com DRC em estágios 4 e 5 pré-dialítico em comparação a dieta restrita em proteínas? EVIDÊNCIAS CLÍNICAS: O demandante apresentou as evidências científicas a partir dos d

HIV-1 subtype F integrase polymorphisms external to the catalytic core domain contribute to severe loss of replication capacity in context of the integrase inhibitor resistance mutation Q148H.

BACKGROUND: In prior studies, HIV-1 BF recombinants with subtype F integrases failed to develop resistance to raltegravir through the Q148H mutational pathway. We aimed to determine the role of subtype-specific polymorphisms in integrase on drug susceptibility, viral replication and integration. METHODS: Integrase sequences were retrieved from the Los Alamos Database or obtained from the Garrahan HIV cohort. HIV-1 infectious molecular clones with or without Q148H (+ G140S) resistance mutations were constructed using integrases of subtype B (NL4-3) or F1(BF) ARMA159 and URTR23. Integrase chimeras were generated by reciprocal exchanges of a 200 bp fragment spanning amino acids 85-150 of the catalytic core domain (CCD) of NL4-3-Q148H and either ARMA159-Q148H or URTR23-Q148H. Viral infections were quantified by p24 ELISA and Alu-gag integration PCR assay. RESULTS: At least 18 different polymorphisms distinguish subtype B from F1(BF) recombinant integrases. In phenotypic experiments, p24 at Day 15 post-infection was high (105-106 pg/mL) for WT and NL4-3-Q148H; by contrast, it was low (102-104 pg/mL) for both F1(BF)-Q148H + G140S viruses, and undetectable for the Q148H mutants. Compared with WT viruses, integrated DNA was reduced by 5-fold for NL4-3-Q148H (P = 0.05), 9-fold for URTR23-Q148H (P = 0.01) and 16000-fold for ARMA159-Q148H (P = 0.01). Reciprocal exchange between B and F1(BF) of an integrase CCD region failed to rescue the replicative defect of F1(BF) integrase mutants. CONCLUSIONS: The functional impairment of Q148H in the context of subtype F integrases from BF recombinants explains the lack of selection of this pathway in vivo. Non-B polymorphisms external to the integrase CCD may influence the pathway to integrase strand transfer inhibitor resistance.

L-lysine: Its antagonism with L-arginine in controlling viral infection. Narrative literature review.

Knowledge about viral characteristics, mechanisms of entry into the host cell and multiplication/dissemination can help in the control and treatment of viral pathologies. Several nutritional factors linked to the host may favour viral multiplication and their control, may lead to new prophylactic alternatives and/or antiviral therapies. The objective of this review is to discuss the relationship between the amino acid L-lysine and the control of viral infections, aiming at a possible therapeutic property. This research used databases such as PubMed, Web of Science, Scielo, Medline and Google Scholar, as well as searching for references cited by journals. The time frame covered the period between 1964 and January 2022. The observed studies have shown that the usual antiviral therapies are not able to interfere with the viruses in their latent state; however, they can interfere with the adhesion and fusion of viral particles or the production of proteins, which play an important role in viral epidemiology and control, particularly in the initial moment and in reactivation. Lysine is an amino acid that can interfere mainly in the formation of capsid proteins and DNA by a competitive antagonism with amino acid arginine, which is an essential amino acid for some viruses, and also by promoting the increase of arginase, increasing the catabolism of arginine. Although there is evidence of the importance of L-lysine in viral control, more studies are needed, with a view to new antiviral therapies.

[Nutritional labeling and amino acid profile in high protein Chilean dairy products: a new alternative for health and sports]. / Etiquetado nutricional y perfil de aminoácidos en lácteos chilenos altos en proteína: nueva alternativa para la salud y el deporte.

INTRODUCTION: Introduction: protein is an essential nutrient that can be obtained through different food sources. In recent years, a growing development in the food industry of dairy products with higher protein content has emerged in the national market. Métodos: the present work analyzed the nutritional information, protein content, and amino acid profile of high protein yogurts. Five main brands of high-protein yogurt (PY) were selected, as was a sample of regular yogurt (RY), and one of whey protein isolate (WP), which underwent a proximal analysis and amino acid profile by high-performance liquid chromatography (HPLC). Results: it was observed that the protein content of the analyzed YP ranged between 7.2 and 15.1 g/portion, representing 6.8 % to 11 % of total content, twice the content of YBAT (3,4 %). Regarding carbohydrates and fats, these were found to range between 6.25 and 13.5 g/serving and 0.9 and 5.3 g/serving, respectively. Leucine content of the PY varied between 0.6 and 1.5 g/portion, which was higher than RY (0.3 g/portion) and lower than WP (2.2 g/portion). The sum of essential amino acids was found to be between 3 and 6.9 g/portion in PY, 1.7 g/serving y 8.5 g/serving in WP. Conclusion: these results show that PYs are a good alternative to promote a correct protein intake, similar to proteins for sports use, so their recommendation could be useful to promote consumption in different populations according to their needs.

INTRODUCCIÓN: Introducción: la proteína es un nutriente esencial que se puede obtener a través de diferentes fuentes alimentarias . En los últimos años, un creciente desarrollo de la industria alimentaria de productos lácteos con mayor aporte en proteínas ha surgido en el mercado nacional. Métodos: el presente trabajo analizó la información nutricional, el contenido proteico y el perfil de aminoácidos de una serie de yogures altos en proteína. Se seleccionaron 5 principales marcas de yogures altos en proteína (YP), una muestra de yogur batido (YBAT) y una de proteina de suero de leche aislado (WP) a las que se realizó un análisis proximal y un perfil de aminoácidos por cromatografía líquida de alto rendimiento (HPLC). Resultados: se pudo observar que el contenido de proteína de los YP analizados varió entre 7,2-15,1 g/porción, lo que representa del 6,8 al 11 % del contenido total, el doble del contenido del YBAT (3,4 %). Respecto a los hidratos de carbono y grasas, estos se encontraron entre 6,25 y 13,5 g/porción y 0,9 y 5,3 g/porción, respectivamente. El contenido de leucina de los YP varió entre 0,6 y 1,5 g/porción, con valores superiores a los de los YBAT (0,3 g/porción) e inferiores a los de las WP (2,2 g/porción). La suma de aminoácidos esenciales se encontró entre 3 y 6,9 g/porción en los YP, en 1,7 g/porción en los YBAT y 8,5 g/porción en las WP. Conclusión: estos resultados demuestran que los YP son una buena alternativa para promover una correcta ingesta proteica, semejante a las proteínas de uso deportivo, por lo que su recomendación podría ser útil para promover su consumo en diferentes poblaciones según sus necesidades.

Cerebrolysin ameliorates prefrontal cortex and hippocampus neural atrophy of spontaneous hypertensive rats with hyperglycemia.

Hyperglycemia of diabetes mellitus causes damage at the vascular level, which at the renal level represents diabetic nephropathy. In this pathology, there is arterial hypertension. In addition, several reports suggest that hyperglycemia and arterial hypertension affect interneuronal communication at the level of dendritic morphology. We studied these changes in an animal model with streptozotocin-induced diabetes mellitus in the spontaneous hypertensive (SH) rat. Recent reports from our laboratory have demonstrated that cerebrolysin (CBL), a preparation of neuropeptides with protective and repairing properties, reduces dendritic deterioration in both pathologies, in separate studies. In the present study, we evaluated the effect of CBL using the animal model with hyperglycemia and arterial hypertension and assessed the dendritic morphology using a Golgi-Cox staining procedure. Our results suggest that CBL ameliorated the reduction in the number of dendritic spines in the PFC and hippocampus caused by hyperglycemia in the SH rat. In addition, CBL also increased distal dendritic length in the PFC and hippocampus in hyperglycemic SH rats. Consequently, the CBL could be a therapeutic tool used to reduce the damage at the level of dendritic communication present in both pathologies.

Cerebrolysin improves peripheral inflammatory pain: Sex differences in two models of acute and chronic mechanical hypersensitivity.

Chronic inflammatory pain is a major health problem worldwide with high prevalence in women. Cerebrolysin is a multimodal neuropeptide preparation that crosses the blood brain barrier and displays neuroprotective properties in aging and disease. Previously, we showed that cerebrolysin reduced mechanical allodynia in a model of persistent inflammation and pain. We aim to build upon the findings of our previous study by investigating the response to acute administration of cerebrolysin in two models of peripheral inflammation and assessing sex differences. We utilized the complete Freund's adjuvant (CFA) that produces maximal oedema and mechanical allodynia within days and carrageenan that produces similar effects within hours. Cerebrolysin reversed the mechanical allodynia in both sexes in CFA-treated rats. On the other hand, in rats treated with carrageenan, cerebrolysin was only effective in reducing mechanical allodynia in female rats. In conclusion, the present study shows that cerebrolysin effects may be sex-specific depending on different mechanisms that are at play in these two models of peripheral inflammatory pain. Further investigations are required to determine the factors contributing to sex differences.

A Case Report on the Use of Pharmacological Intervention in the Treatment of Diffuse Axonal Injury From Road Traffic Accidents.

We report a case of traumatic brain injury treated with Cerebrolysin, a neurorecovery stimulating agent. Our therapeutic approach was based on the pathophysiology of traumatic brain injury and, in particular, of diffuse axonal injury. The patient registered marked improvement in mood and cognitive performance, indicating the effectiveness of multimodal and multidisciplinary interventions after traumatic brain injury.

Keto analogues and amino acid supplementation and its effects on ammonaemia during extenuating endurance exercise in ketogenic diet-fed rats.

Keto analogues and amino acids (KAAA) supplementation can reduce blood ammonia concentrations in athletes undergoing high-intensity exercise under both ketogenic and thermoneutral conditions. This study evaluated the acute effects of KAAA supplementation on ammonia metabolism during extenuating endurance exercise in rats fed a ketogenic diet. In all, eighty male Fischer rats at 90 d of age were divided into eight groups, and some were trained using a swimming endurance protocol. A ketogenic diet supplemented with keto analogues was administered for 10 d. Administration of the ketogenic diet ended 3 d before the exhaustion test (extenuating endurance exercise). A ketogenic diet plus KAAA supplementation and extenuating endurance exercise (trained ketogenic diet supplemented with KAAA (TKKa)) increased blood ammonia concentrations by approximately 50 % compared with the control diet (trained control diet supplemented with KAAA (TCKa)) and similar training (effect size=1·33; statistical power=0·50). The KAAA supplementation reduced blood urea concentrations by 4 and 18 % in the control and ketogenic diet groups, respectively, compared with the groups fed the same diets without supplementation. The trained groups had 60 % lower blood urate concentrations after TCKa treatment than after TKKa treatment. Our results suggest that KAAA supplementation can reduce blood ammonia concentrations after extenuating endurance exercise in rats fed a balanced diet but not in rats fed a ketogenic diet.

Análisis de la solicitud de inclusión de nutrición parenteral a base de lípidos, aminoácidos, glucosa, electrolitos / Analysis of the request for inclusion of parenteral nutrition based on lipids, amino acids, glucose, electrolytes

INTRODUCCIÓN: La desnutrición relacionada con la enfermedad es uno de los principales problemas de salud pública. Un adecuado soporte nutricional al paciente hospitalizado es parte integral de tratamiento, cuyo propósito final es restablecer la salud, evitar complicaciones y disminuir la duración de la estancia hospitalaria1 . La nutrición parenteral (NP) aporta los nutrientes necesarios para la alimentación, como parte de los requerimientos en diversas patologías. La NP se define como la administración intravenosa de nutrientes, agua, electrolitos y vitaminas requeridos debido a la presencia persistente de falla intestinal. Sin embargo, antes de su utilización es importante realizar una evaluación adecuada de los pacientes y así asegurar que la alimentación por medio del tracto gastrointestinal no es posible o no puede ser optimizada. Se utilizan varios tipos de emulsiones lipídicas en la NP: las basadas en aceite de soya (triglicéridos de cadena larga [LCT, por sus siglas en inglés]), las que incorporan triglicéridos de cadena media (MCT, por sus siglas en inglés), las mezclas de LCT-MCT (emulsiones de aceite de oliva y soya [80/20]) y las que incorporan ácidos grasos omega-3 de los aceites de pescado (emulsiones MSF: MCT / Soya / Pescado, 50:40:10, y SMOF: Soya / MCT / Oliva / Pescado, 30:30:25:15). La nutrición parenteral, lípidos intravenosos de soya y oliva, aminoácidos cristalinos con electrolitos y glucosa con calcio (NP oliva / soya) es una mezcla LCT-MCT que contiene una proporción de aceite de oliva y soya (80:20) con reducción de la carga de ácidos grasos esenciales ω-6 (ácido linoleico u omega-6) en comparación con la NP con aceite de soya (NP soya) que contiene omega-6. La NP oliva / soya proporciona un apoyo nutricional para mantener el balance de nitrógeno / energía que puede alterarse por la malnutrición y la enfermedad del paciente. NP oliva / soya proporciona una fuente de nitrógeno (L-aminoácidos), energía (como glucosa y lípidos), ácidos grasos esenciales y electrolitos, biológicamente disponibles5 . El uso de la NP oliva / soya en la alimentación parenteral especializada para pacientes cuando la alimentación oral o enteral es imposible, insuficiente o está contraindicada, se encuentra aprobado por la Comisión Federal para la Protección contra Riesgos Sanitarios [COFEPRIS]6 y por agencias internacionales (Agencia Española de Medicamentos y Productos sanitarios [AEMPS]7 y Medicines and Healthcare Products Regulatory Agency [MHRA]). EVALUACIONES DE TECNOLOGÍAS: No se encontraron reportes de evaluación de tecnologías para NP oliva / soya. IMPLICACIONES ECONÓMICAS Se presentó una evaluación económica12 de tipo minimización de costos del uso de la NP oliva / soya, desde la perspectiva del pagador de servicios públicos de salud en un horizonte temporal de 9 y 11 días, como comparadores se incluyeron las bolsas preparadas en el hospital (cuyos requerimientos fueron establecidos por los expertos clínicos), y bolsas tricámara incluidas en el Cuadro Básico y Catálogo de Medicamentos (claves: 5388 y 5389)13 como NP. Para estimar el costeo a partir de los requerimientos nutricionales de un paciente que necesita NP, se definieron dos casos: CASO 1. Paciente adulto de 70 kg de peso, estatura promedio de 167 cm, con alta demanda metabólica en (o con) alto riesgo de desnutrición, al que no le ha sido posible alcanzar más del 60% de los requerimientos energéticos por vía enteral y requiere la complementación de su alimentación a través de NP. CASO 2. Paciente adulto en periodo preoperatorio (7 a 10 días antes de la intervención) con desnutrición grave que no tolera la vía oral o la nutrición enteral. Adicionalmente, se realizó un análisis de sensibilidad determinístico sobre el precio de NP oliva / soya en ± 2% y ± 3%. Los resultados indican que NP oliva / soya es una opción costo ahorradora en comparación con las otras opciones de NP. Para ambos casos la diferencia en los costos asociados a la NP es con las nutriciones parenterales preparadas en el hospital, para 9 y 11 días de administración de NP, con un ahorro, a favor de NP oliva / soya tanto en caso 1 como en caso 2. Los resultados del análisis de sensibilidad indican que a pesar de los descuentos y aumentos al precio de la NP oliva / soya, esta se mantiene como una opción costo ahorradora. Sin embargo, se deben tomar en cuenta las siguientes consideraciones: Una limitación del estudio, es la falta de información epidemiológica nacional que describa el uso de nutriciones parenterales en el ámbito hospitalario. Por lo que, entre los supuestos establecidos a través de un panel de expertos, considerando que la concentración de glucosa definida (50%) es mayor que la incluida en NP oliva / soya (glucosa al 20%), y que la cantidad de lípidos y aminoácidos establecida como requerimiento para cada tipo de pacientes es alta de acuerdo al volumen de requerimiento total, por lo que el costo total de la NP elaborada en el hospital podría estar subestimado. NP oliva / soya tiene menor concentración de lípidos y aminoácidos en comparación con la NP con clave 5388 y 5389, por lo que el supuesto de igual eficacia (para cubrir requerimientos nutricionales) no tiene sustento clínico.

Effects of l-Arginine supplementation on lactating mares and the development of foals

Background: Most animal species are able to produce Arginine (Arg) under normal conditions. However, in some situations, its degradation can be higher than its production. For example, during a period of lactation or disease, there is an increase in the consumption of Arg. In this case, endogenous production is not enough for the animals demands. Indeed, Arg supplementation in animals has several benefits for the animals body, such as the increase of angiogenesis, improvements in immunity and the reproductive system, as well as the stimulation of lactogenesis. During the early phase of growth, a deficiency of Arg could cause a reduction in the growth rate and metabolic activity of animals. Therefore, this amino acid is considered essential in some phases of the life of animals. However, very few studies of the supplementation of this amino acid in horses have been carried out. The aim of the present study was to characterize the effects of supplementing lactating mares and their foals with Arg. Materials, Methods & Results: Lactating mares (n = 10) were divided into two groups (control group: n = 3 / supplemented group: n = 7) and maintained exclusively under grazing. The supplemented group received 50 g of Arg during the lactation period. Samples of milk and blood from mares and blood from foals were collected at different phases of the lactation period. The following [...](AU)

Effects of l-Arginine supplementation on lactating mares and the development of foals

Background: Most animal species are able to produce Arginine (Arg) under normal conditions. However, in some situations, its degradation can be higher than its production. For example, during a period of lactation or disease, there is an increase in the consumption of Arg. In this case, endogenous production is not enough for the animals demands. Indeed, Arg supplementation in animals has several benefits for the animals body, such as the increase of angiogenesis, improvements in immunity and the reproductive system, as well as the stimulation of lactogenesis. During the early phase of growth, a deficiency of Arg could cause a reduction in the growth rate and metabolic activity of animals. Therefore, this amino acid is considered essential in some phases of the life of animals. However, very few studies of the supplementation of this amino acid in horses have been carried out. The aim of the present study was to characterize the effects of supplementing lactating mares and their foals with Arg. Materials, Methods & Results: Lactating mares (n = 10) were divided into two groups (control group: n = 3 / supplemented group: n = 7) and maintained exclusively under grazing. The supplemented group received 50 g of Arg during the lactation period. Samples of milk and blood from mares and blood from foals were collected at different phases of the lactation period. The following [...]

Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics / Bloqueio do Sistema Renina-Angiotensina Associado a Estatina Melhora a Função Endotelial em Diabéticos

Abstract Background: Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness. Objective: To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness. Methods: Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively). Results: The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586). Conclusion: Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Resumo Fundamentos: Estudos sugerem que as estatinas possuem efeitos pleotrópicos, como melhora da função endotelial, da rigidez vascular e redução da pressão arterial. Objetivo: Analisar se o uso prévio de estatina influenciou o efeito sobre a pressão arterial, a função endotelial e a rigidez vascular de drogas inibidoras do sistema renina-angiotensina-aldosterona. Métodos: Pacientes hipertensos e diabéticos com pressão arterial de consultório sistólica ≥ 130 mmHg e/ou diastólica ≥ 80 mmHg tiveram suas medicações anti-hipertensivas substituídas por anlodipino durante 6 semanas. Em seguida, foram randomizados para associação de benazepril ou losartana por mais 12 semanas. Pressão arterial (através da monitorização ambulatorial da pressão arterial), função endotelial (dilatação mediada por fluxo da artéria braquial) e rigidez vascular (velocidade da onda de pulso) foram avaliados antes e após o tratamento combinado. Neste trabalho, uma análise post-hoc foi realizada para comparar pacientes que vinham (grupo CE) ou não (grupo SE) em uso de estatina. Resultados: O grupo CE apresentou maior redução na pressão arterial sistólica nas 24 horas (134 para 122 mmHg, p = 0,007) e na dilatação mediada por fluxo da artéria braquial (6,5 para 10,9%, p = 0,003) quando comparado com o grupo SE (137 para 128 mmHg, p = 0,362, e 7,5 para 8,3%, p = 0,820). Não houve diferença estatisticamente significante na velocidade de onda de pulso (grupo CE 9,95 para 9,90 m/s, p = 0,650 e grupo SE 10,65 para 11,05 m/s, p = 0,586). Conclusão: O uso combinado de estatinas, anlodipino e inibidores do sistema renina-angiotensina-aldosterona melhora a resposta anti-hipertensiva e a função endotelial em pacientes hipertensos e diabéticos.

Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics.

BACKGROUND: Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness. OBJECTIVE: To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness. METHODS: Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively). RESULTS: The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586). CONCLUSION: Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. OBJECTIVES: To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. SELECTION CRITERIA: Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. MAIN RESULTS: We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. AUTHORS' CONCLUSIONS: This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

Effect of a protein-free diet in the development of food allergy and oral tolerance in BALB/c mice.

The aim of the present study was to investigate the effect of a protein-free diet in the induction of food allergy and oral tolerance in BALB/c mice. The experimental model used was mice that were fed, since weaning up to adulthood, a balanced diet in which all dietary proteins were replaced by amino acid diet (Aa). The absence of dietary proteins did not prevent the development of food allergy to ovalbumin (OVA) in these mice. However, Aa-fed mice produced lower levels of IgE, secretory IgA and cytokines. In addition, when compared with mice from control group, Aa-fed mice had a milder aversive reaction to the allergen measured by consumption of OVA-containing solution and weight loss during food allergy development. In addition, mice that did not have dietary proteins in their diets were less susceptible to induction of oral tolerance. One single oral administration was not enough to suppress specific serum Ig and IgG1 levels in the Aa-fed group, although it was efficient to induce suppression in the control group. The present results indicate that the stimulation by dietary proteins alters both inflammatory reactivity and regulatory immune reactivity in mice probably due to their effect in the maturation of the immune system.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease.

BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Patients with liver disease frequently have haemostatic abnormalities like hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in patients with liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (11 June 2012), Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2012, Issue 5 of 12), MEDLINE (Ovid SP) (1946 to June 2012), EMBASE (Ovid SP) (1974 to June 2012), Science Citation Index EXPANDED (1900 to June 2012), LILACS (1982 to June 2012), Clinical Trials Search Portal of the WHO (accessed June 18, 2012), and the Metaregister of Controlled Trials (accessed June 18, 2012). We scrutinised the reference lists of the retrieved publications. SELECTION CRITERIA: Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. DATA COLLECTION AND ANALYSIS: Data from randomised clinical trials were to be summarised by standard Cochrane Collaboration methodologies. MAIN RESULTS: We could not find any randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in patients with acute or chronic liver disease. We could not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. AUTHORS' CONCLUSIONS: No randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease were identified. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade off between benefits and harms, we cannot recommend nor refute antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver diseases.

Cerebrolysin improves symptoms and delays progression in patients with Alzheimer's disease and vascular dementia.

Dementia is the result of various cerebral disorders, leading to an acquired loss of memory and impaired cognitive ability. The most common forms are Alzheimer's disease (AD) and vascular dementia (VaD). Neurotrophic factors are essential for the survival and differentiation of developing neurons and protecting them against damage under pathologic conditions. Cerebrolysin is a peptide preparation that mimics the pleiotropic effects of neurotrophic factors. Several clinical trials investigating the therapeutic efficacy of Cerebrolysin in AD and VaD have confirmed the proof of concept. The results of these trials have shown statistically significant and clinically relevant treatment effects of Cerebrolysin on cognitive, global and functional domains in mild to moderately severe stages of dementia. Doses of 10 and 30 mL were the most effective, but higher doses of up to 60 mL turned out to be most effective in improving neuropsychiatric symptoms, which become relevant at later stages of the disease. Combining treatment with cholinesterase inhibitors and Cerebrolysin indicated long-term synergistic treatment effects in mild to moderate AD. The efficacy of Cerebrolysin persisted for up to several months after treatment suggesting Cerebrolysin has not merely symptomatic benefits, but a disease-delaying potential. This paper reviews the clinical efficacy of Cerebrolysin in the treatment of dementia. Data were obtained from international, multicenter, randomized clinical trials performed in compliance with Good Clinical Practice and the principles of the Declaration of Helsinki (1964) and subsequent revisions.