Dietas artificiais para a criação de larvas e adultos da mosca-das-frutas sul-americana

O objetivo deste trabalho foi adequar as dietas artificiais para o desenvolvimento dos estágios de larva e adulto da mosca-das-frutas sul-americana (Anastrepha fraterculus). Para o estágio larval, foram testadas as seguintes dietas: D1, original, com 10 g de ágar; D2, modificada, com 3,6 g de ágar; e, D3, modificada, com bagaço seco de cana-de-açúcar. Para os adultos, foram testadas quatro dietas: A, levedura de cerveja + mel (2:1); B, açúcar refinado + extrato de levedura + gérmen de trigo cru (3:1:1); C, extrato de soja + açúcar mascavo + gérmen de trigo cru (3:1:1); e D, levedura seca de cervejaria + mel (2:1). Avaliaram-se os parâmetros biológicos de duração do período ovo-pupa, duração e viabilidade do estágio de pupa, massa média de pupas, razão sexual e duração e viabilidade do período ovo-adulto. O desenvolvimento larval em D1 e D2 foi semelhante e indicou que a criação de larvas pode ser realizada com 1/3 da quantidade de ágar da utilizada em D1. A utilização do bagaço seco de cana-de-açúcar, na dieta artificial, afetou negativamente o desenvolvimento larval. As dietas artificiais com levedura de cerveja + mel e com açúcar refinado + extrato de levedura + gérmen de trigo cru são as mais adequadas para a criação de adultos.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Biologia de ninfas e adultos do percevejo-verde em estruturas reprodutivas de algodoeiro

O objetivo deste trabalho foi determinar a biologia de ninfas e adultos do percevejo-verde em estruturas reprodutivas do algodoeiro. Os alimentos testados foram: dieta padrão, contendo vagem de feijão, amendoim cru e frutos de ligustro; vagem verde de soja; semente de soja; botão floral de algodoeiro; e maçãs e sementes de algodoeiro. Foram avaliados os parâmetros biológicos: período de desenvolvimento e sobrevivência ninfal; longevidade de fêmeas e machos; percentagem de fêmeas em oviposição; períodos de pré-oviposição e oviposição; número total de ovos por fêmea; e viabilidade dos ovos. Ninfas alimentadas com estruturas reprodutivas do algodoeiro morreram no segundo ou no terceiro ínstar. Adultos alimentados com botão floral e semente de algodoeiro não se reproduzem; porém, há reprodução quando adultos os de percevejo-verde são alimentados com maçã de algodoeiro, o que indica a capacidade de adaptação da espécie na fase reprodutiva do algodoeiro.

Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.

Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-β 1-42 (Aβ42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF Aβ42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to Aβ42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.

Personality traits, behavioral and psychological symptoms and cognitive decline in patients at an early stage of Alzheimer's disease

The aim of this doctoral thesis was to study personality characteristics of patients at an early stage of Alzheimer's disease (AD), and more specifically to describe personality and its changes over time, and to explore its possible links with psychological and symptoms (BPS) and cognitive level. The results were compared to those of a group of participants without cognitive disorder through three empirical studies. In the first study, the findings showed significant personality changes that follow a specific trend in the clinical group. The profil of personality changes showed an increase in Neuroticism and a decrease in Extraversion, Openess to experiences, and Conscientiousness over time. The second study highlighted that personality and BPS occur early in the cours of AD. Recognizing them as possible precoce signs of neurodegeneration may prove to be a key factor for early detection and intervention. In the third study, a significant association between personality changes and cognitive status was observed in the patients with incipient AD. Thus, changes in Neuroticism and Conscientiousness were linked with cognitive deterioration, whereas decreased Openness to experiences and Conscientiousness over time predicted loss of independence in daily functioning. Other well-known factors such as age, education level or civil status were taken into account to predict cognitive decline. The three studies suggested five important implications: (1) cost-effective screening should take into account premorbid and specific personality changes; (2) psycho-educative interventions should provide information on the possible personality changes and BPS that may occur at the beginning of the disease; (3) using personality traits alongside other variables in the future studies on prevention might help to better understand AD's etiology; (4) individual treatment plans (psychotherapeutic, social, and pharmacological) might be adapted to the specific changes in personality profiles; (5) more researches are needed to study the impact of social-cultural and lifestyle variables on the development of AD.

Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer's disease.

The distribution of immunoreactivity for the neurofilament triplet class of intermediate filament proteins was examined in the hippocampus of young, adult and elderly control cases and compared to that of Alzheimer's disease cases. In a similar fashion to non-human mammalian species, pyramidal neurons in the CA1 region showed a very low degree of neurofilament triplet immunoreactivity in the three younger control cases examined. However, in the other control cases of 49 years of age and older, many CA1 pyramidal neurons showed elevated neurofilament immunoreactivity. In the Alzheimer's disease cases, most of the surviving CA1 neurons showed intense labeling for the neurofilament triplet proteins, with many of these neurons giving off abnormal "sprouting" processes. Double labeling demonstrated that many of these neurons contained tangle-like or granular material that was immunoreactive for abnormal forms of tau and stained with thioflavine S, indicating that these neurons are in a transitional degenerative stage. An antibody to phosphorylated neurofilament proteins labeled a subset of neurofibrillary tangles in the Alzheimer's disease cases. However, following formic acid pre-treatment, the number of neurofibrillary tangles showing phosphorylated neurofilament protein immunoreactivity increased, with double labeling confirming that all of the tau-immunoreactive neurofibrillary tangles were also immunoreactive for phosphorylated neurofilament proteins. Immunoblotting demonstrated that there was a proportionately greater amount of the neurofilament triplet subunit proteins in hippocampal tissue from Alzheimer's disease cases as compared to controls. These results indicate that there are changes in the cytoskeleton of CA1 neurons associated with age which are likely to involve an increase in the level of neurofilament proteins and may be a predisposing factor contributing towards their high degree of vulnerability in degenerative conditions such as Alzheimer's disease. The cellular factors affecting hippocampal neurons during aging may be potentiated in Alzheimer's disease to result in even higher levels of intracellular neurofilament proteins and the progressive alterations of neurofilaments and other cytoskeletal proteins that finally results in neurofibrillary tangle formation and cellular degeneration.

Atratividade e preferência alimentar de adultos de Epicauta atomaria (Germ., 1821) (Col.: Meloidae) em maracujazeiros (Passiflora spp.), sob condições de laboratório

A atratividade e a preferência alimentar de adultos de Epicauta atomaria (Germ., 1821) por folhas de espécies de maracujazeiro Passiflora spp. foram avaliadas sob condições de laboratório. Em testes de atratividade realizados em placas de Petri e olfatômetro, os discos foliares e extratos foliares de P. setacea e P. edulis f. flavicarpa foram os mais preferidos por adultos de E. atomaria, enquanto P. giberti, P. nitida e P. alata foram os menos preferidas nos dois tipos de recipientes. Nos testes de consumo com e sem chance de escolha utilizando discos foliares, P. setacea foi a mais consumida, confirmando sua suscetibilidade; P. giberti e P. nitida foram pouco consumidas, apresentando não-preferência para alimentação como mecanismo de resistência; P. edulis f. flavicarpa e P. alata também revelaram não-preferência para alimentação, porém em níveis mais baixos.

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

We have synthesized a family of rheinhuprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and ()-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and ()-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and ()-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

We have synthesized a family of rheinhuprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and ()-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and ()-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and ()-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

Alateraciones de la memoria implícita y explícita en el envejecimiento natural y en la demencia tipo Alzheimer

L’esperança de vida ha millorat en aquest darrer segle, al mateix temps, han augmentat les malalties neurodegeneratives, sent l’Alzheimer el seu màxim exponent, caracteritzant-se per una important pèrdua de memòria. Davant d’aquesta realitat, l’objectiu últim d’aquest treball, és corroborar que les alteracions de memòria (explícita i implícita) no formen part del procés d’envelliment natural. Per a tal propòsit, després d’assentar els aspectes generals sobre la memòria, ens centrarem amb l’anàlisi de les alteracions que es produeixen en la memòria explícita i implícita, tant durant el procés d’envelliment natural, com en el patològic, particularment en el cas de la malaltia d’Alzheimer. Per arribar a una conclusió fefaent, s'efectuarà un minuciós i crític estudi, revisant la literatura específica i científica existent.

Rapid improvement of canine cognitive dysfunction with immunotherapy designed for Alzheimer's disease

Immunotherapy against amyloid-β(Aβ) may improve rodent cognitive function by reducing amyloid neuropathology and is being validated in clinical trials with positive preliminary results. However, for a complete understanding of the direct and long-term immunization responses in the aged patient, and also to avoid significant side effects, several key aspects remain to be clarified. Thus, to investigate brain Aβ clearance and Th2 responses in the elderly, and the reverse inflammatory events not found in the immunized rodent, better Alzheimer"s disease (AD) models are required. In the aged familiar canine with a Cognitive Dysfunction Syndrome (CDS) we describe the rapid effectiveness and the full safety profile of a new active vaccine candidate for human AD prevention and treatment. In these aged animals, besidesa weak immune system, the antibody response activated a coordinated central and peripheral Aβ clearance, that rapidly improved their cognitive function in absence of any side effects. Our results also confirm the interest to use familiar dogs to develop innovative and reliable therapies for AD.

El Sentido de la Vida y el Deseo de Adelantar la Muerte en pacientes con procesos avanzados de enfermedad

El deseo de adelantar la muerte (DAM) no es infrecuente en la población paliativa o con cáncer avanzado. Las evidencias actuales muestran el DAM como una respuesta reactiva al sufrimiento multidimensional propio del paciente en con procesos avanzados de enfermedad. Tras estudiar los factores relacionados con el DAM, se ha observado que la variable sentido de la vida (SV), desempeña un rol importante en relación al desencadenamiento del DAM. Hasta el momento se han publicado diversas intervenciones dirigidas a ayudar a los pacientes en la búsqueda o mejora de SV en el tramo final de sus vidas. Sin embargo no se ha evaluado la eficacia de estas intervenciones sobre el DAM. El objetivo principal del presente estudio es evaluar, en una población de pacientes en cuidados paliativos, la efectividad de una intervención de mejora del SV para disminuir el eventual DAM. El estudio se desarrollará en tres fases. En primer lugar se realizará una revisión sistemática integrativa de las intervenciones publicadas para mejorar el SV y posterior selección de la terapia más adecuada de acuerdo con las evidencias halladas. En segundo lugar se hará la adaptación transcultural y validación de un instrumento de medida de SV, el Meaning in Life Questionnaire (MLQ). Por último se llevará a cabo la implementación de la intervención escogida y evaluación de su efectividad para disminuir el DAM, mediante un estudio de diseño pre-post, en pacientes oncológicos ingresados en la unidad de cuidados paliativos. Este trabajo aportará también los resultados preliminares de la revisión sistemática integrativa de las intervenciones de SV.

Medida de la personalidad en los adultos mediante el EQP y el 16PF y su relación con las actiudes sociales

En este estudio se pretende averiguar la relación que existe entre las dimensiones de personalidad de Eysenck (Neuroticismo, Extraversión y Psicoticismo) con los 16 factores primarios de Cattell, en una muestra homogénea de personas que no presentan trastornos de personalidad ni psicopatología psiquiátrica. También nos proponemos estudiar la relación entre las actitudes hacia valores sociales (liberalismo-conservadurismo) y la personalidad medida por el EPQ y el 16PF. Los resultados informan de diferencias importantes de personalidad entre hombres y mujeres, de una relación entre el Neuroticismo de Eysenck y los factores de ansiedad de Cattell (C-,O+ y Q4+), entre la Extraversión con E+, H+, F+, A+ y Q2- y entre Psicoticismo con I- y L+, de lo que se concluye la existencia de una gran homogeneidad psicológica entre las dos medidas de la personalidad. Los Liberales son más estables (C+), menos socializados (G-), más imaginativos (M+), menos astutos (N-), menos respetuosos con las ideas establecidas (Q1-), menos neuróticos (Ne-) y más inconformistas (S+).