Estado nutricional e consumo alimentar de pacientes brasileiros em diferentes estágios da doença de alzheimer: um estudo transversal / Nutritional status and food intake of Brazilian patients at various stages of Alzheimer's disease: a cross-sectional study

A doença de Alzheimer (DA) é caracterizada por distúrbios que podem comprometer a nutrição do paciente e causar perda de peso e deficiências nutricionais durante a doença. O objetivo deste estudo foi avaliar o estado nutricional e o consumo alimentar de pacientes brasileiros com doença de Alzheimer em diferentes estágios da doença. A amostra foi composta por 30 indivíduos, com idade média de 77 anos, de ambos os sexos, com provável DA. Os indivíduos foram avaliados através de dados antropométricos, Mini Avaliação Nutricional (MAN), albumina sérica, Mini Exame do Estado Mental, e recordatório de 24 horas. Embora tenha sido encontrada uma diminuição no peso médio entre os estágios da doença (CDR1: 70,8±15,9 kg; CDR2: 61,4±15,7 kg; CDR3: 56,1± 8,4kg) conforme a progressão da doença, a diferença não foi significativa. Os parâmetros MAN e albumina sérica mostraram uma diminuição entre os estágios da doença (p = 0,042,p = 0,047, respectivamente), sendo que no estágio grave metade dos pacientes estava desnutrida e a outra metade em risco de desnutrição. De acordo com o índice de massa corporal, 23,3% dos pacientes estavam com sobrepeso. O valor nutricional da ingestão alimentar foi similar nos estágios de DA. Em conclusão, a maioria dos pacientes brasileiros com DA neste estudo apresentaram desnutrição, apesar de o consumo alimentar ter sido similar entre os estágios da doença, uma vez que não apresentou associação direta com a progressão da DA...

Alzheimer's disease (AD) is characterized by disorders that can impair the nutrition of the patient and lead to weight loss and nutritional deficits during the course of the disease. The aim of this study was to assess the nutritional status and food intake of Brazilian patients with Alzheimer's disease at 3 different stages of the disease. The sample consisted of 30 subjects of both genders, mean age 77 years, with probable AD. Subjects were assessed by collecting anthropometric data, the Mini Nutritional Assessment (MNA), serum albumin content, Mini Mental State Examination and 24-hour records of food and drink. Although a steady decrease in average weight was observed as the disease progressed (CDR1: 70.8±15.9 kg; CDR2: 61.4±15.7 kg; CDR3: 56.1± 8.4 kg), the differences were not significant. MNA and serum albumin both fell during the progression of the disease (p = 0.042; p = 0.047, respectively) and, at the severe stage, half the patients were found to be undernourished and the other half at risk of undernutrition. According to their body mass index, 23.3% of patients were overweight. The nutritional value of the food consumed was similar across the stages of AD. In conclusion, the majority of Brazilian patients with AD in this study exhibited cognitive decline and malnutrition. However, food intake was similar among the stages of the disease, thus having no direct association with the progression of AD...

On the participation of hippocampal PKC in acquisition, consolidation and reconsolidation of spatial memory.

Memory consolidation involves a sequence of temporally defined and highly regulated changes in the activation state of several signaling pathways that leads to the lasting storage of an initially labile trace. Despite appearances, consolidation does not make memories permanent. It is now known that upon retrieval well-consolidated memories can become again vulnerable to the action of amnesic agents and in order to persist must undergo a protein synthesis-dependent process named reconsolidation. Experiments with genetically modified animals suggest that some PKC isoforms are important for spatial memory and earlier studies indicate that several PKC substrates are activated following spatial learning. Nevertheless, none of the reports published so far analyzed pharmacologically the role played by PKC during spatial memory processing. Using the conventional PKC and PKCmu inhibitor 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrollo[3,4-c]carbazole (Gö6976) we found that the activity of these kinases is required in the CA1 region of the rat dorsal hippocampus for acquisition and consolidation of spatial memory in the Morris water maze learning task. Our results also show that when infused into dorsal CA1 after non-reinforced retrieval, Gö6976 produces a long-lasting amnesia that is independent of the strength of the memory trace, suggesting that post-retrieval activation of hippocampal PKC is essential for persistence of spatial memory.

The connection between the hippocampal and the striatal memory systems of the brain: a review of recent findings.

Two major memory systems have been recognized over the years (Squire, in Memory and Brain, 1987): the declarative memory system, which is under the control of the hippocampus and related temporal lobe structures, and the procedural or habit memory system, which is under the control of the striatum and its connections (Mishkin et al., in Neurobiology of Learning by G Lynch et al., 1984; Knowlton et al., Science 273:1399, 1996). Most if not all learning tasks studied in animals, however, involve either the performance or the suppression of movement. Animals acquire connections between environmental or discrete sensory cues (conditioned stimuli, CSs) and emotionally or otherwise significant stimuli (unconditioned stimuli, USs). As a result, they learn to perform or to inhibit the performance of certain motor responses to the CS which, when learned well, become what can only be called habits (Mishkin et al., 1984): to regularly walk or swim to a place or away from a place, or to inhibit one or several forms of movement. These responses can be viewed as conditioned responses (CRs) and may sometimes be very complex. This is of course also seen in humans: people learn how to play on a keyboard in response to a mental or written script and perform the piano or write a text; with practice, the performance improves and eventually reaches a high criterion and becomes a habit, performed almost if not completely without awareness. Commuting to school in a big city in the shortest possible time and eschewing the dangers is a complex learning that children acquire to the point of near-perfection. It is agreed that the rules that connect the perception of the CS and the expression of the CR change from their first association to those that take place when the task is mastered. Does this change of rules involve a switch from one memory system to another? Are different brain systems used the first time one plays a sonata or goes to school as compared with the 100th time? Here we will comment on: 1) reversal learning in the Morris water maze (MWM), in which the declarative or spatial component of a task is changed but the procedural component (to swim) persists and needs to be re-linked with a different set of spatial cues; and 2) a series of observations on an inhibitory avoidance task that indicate that the brain systems involved change with further learning.

AMPA/kainate and group-I metabotropic receptor antagonists infused into different brain areas impair memory formation of inhibitory avoidance in rats.

Several lines of evidence suggest that glutamate receptors are involved in memory processing. To examine the role of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors on memory consolidation, rats were bilaterally implanted with cannulae aimed at the CA1 region of the dorsal hippocampus (CA1), entorhinal cortex (ENTO), posterior parietal cortex (PPC) or the basolateral nucleus of the amygdala (BLA), and trained in a one-trial step-down inhibitory avoidance task. At different times after training, the alpha-amino 3-hydroxy-5 methyl 4-isoxazole propionate (AMPA) receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (1.0 microg/side), or the metabotropic type-I receptor antagonist, 2-amino-3-phosphonopropionic acid (AP3) (1.0 microg/side), were infused into the above-mentioned structures. CNQX produced retrograde amnesia when infused into BLA or CA1 0, 30, 90 or 180 min post-training but not at later times. AP3 blocked memory consolidation when administered into CA1 0, 30 or 180 min post-training, while in BLA, it was amnestic only when given 0 or 30 min after the training session. CNQX and AP3 had no effect on memory when administered into ENTO or PPC at any time. Our data suggest that the consolidation of the avoidance memory requires intact non-NMDA receptor function in the hippocampus and the basolateral nucleus of the amygdala, but not necessarily in the entorhinal and parietal cortex, for long periods after training.

Design and implementation of a measuring campaign to model pesticide impacts in an Ecuadorian watershed.

The first important issue in pesticide assessment for a watershed is the availability of soil and water quality information in the form of charts, maps or records. However, developing countries generally do not have enough historical data. Thus, sampling programs are crucial for the success of the evaluation, although in developing countries they always represent a controversial task between limited available budget and a precise assessment. This paper shows the steps taken to generate soil and water data to be used in a pesticide assessment project for a 34,000 ha watershed in Ecuador, South America. Sampling campaigns are still being run, so the methodology and the first results are shown here.

Trace amines: identification of a family of mammalian G protein-coupled receptors.

Tyramine, beta-phenylethylamine, tryptamine, and octopamine are biogenic amines present in trace levels in mammalian nervous systems. Although some "trace amines" have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues. Together with the orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct from, but related to the classical biogenic amine receptors. We have demonstrated that two of these receptors bind and/or are activated by trace amines. The cloning of mammalian GPCRs for trace amines supports a role for trace amines as neurotransmitters in vertebrates. Three of the four human receptors from this family are present in the amygdala, possibly linking trace amine receptors to affective disorders. The identification of this family of receptors should rekindle the investigation of the roles of trace amines in mammalian nervous systems and may potentially lead to the development of novel therapeutics for a variety of indications.

Identification and characterization of two G protein-coupled receptors for neuropeptide FF.

The central nervous system octapeptide, neuropeptide FF (NPFF), is believed to play a role in pain modulation and opiate tolerance. Two G protein-coupled receptors, NPFF1 and NPFF2, were isolated from human and rat central nervous system tissues. NPFF specifically bound to NPFF1 (K(d) = 1.13 nm) and NPFF2 (K(d) = 0.37 nm), and both receptors were activated by NPFF in a variety of heterologous expression systems. The localization of mRNA and binding sites of these receptors in the dorsal horn of the spinal cord, the lateral hypothalamus, the spinal trigeminal nuclei, and the thalamic nuclei supports a role for NPFF in pain modulation. Among the receptors with the highest amino acid sequence homology to NPFF1 and NPFF2 are members of the orexin, NPY, and cholecystokinin families, which have been implicated in feeding. These similarities together with the finding that BIBP3226, an anorexigenic Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF1 in feeding. The identification of NPFF1 and NPFF2 will help delineate their roles in these and other physiological functions.

Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system.

Two structurally related, G-protein-coupled receptors were identified as receptors for the neuropeptide, neuromedin U. This peptide is found in highest levels in the gut and genitourinary system where it potently contracts smooth muscle but is also expressed in the spinal cord and discrete regions of the brain. Binding sites for neuromedin U have been characterized in rat uterus, however, little is known about the activity of this peptide in the regions of the central nervous system where it is expressed. The receptors characterized in this report are activated by neuromedin U at nanomolar potency in heterologous expression systems and bind radiolabeled neuromedin U with high affinity. Localization of the receptor RNA by quantitative reverse transcription-polymerase chain reaction in a variety of human tissues shows distinct expression patterns for the two receptors. NMU1 is expressed predominantly in peripheral tissues, whereas NMU2 is more highly expressed in the central nervous system. Identification of neuromedin U receptor subtypes will greatly aid in the determination of the physiological roles of this peptide.

Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3.

Chemokines mediate their chemotactic, proinflammatory effects by binding to and activating a variety of specific receptors belonging to the G protein-coupled superfamily of seven-transmembrane serpentine receptors. We report the cloning, chromosomal localization, expression, and ligand binding of a novel CC chemokine receptor, CCR10. CCR10 is expressed primarily in placenta and fetal liver, and binds two of the CC chemokines, monocyte chemoattractant protein (MCP)-1 and MCP-3, with highest affinity. The KD for MCP-3 binding was 1 nM, and MCP-1 competed for MCP-3 binding with an IC50 of 1.2 nM. The CC chemokines MCP-4 and RANTES competed for MCP-3 binding with IC50 values of 7.5 and 5.4 nM, respectively. The chromosomal location of CCR10 was determined to coincide with the CC chemokine receptor cluster on chromosome 3 (3p21.31-3p21.32). These results indicate that CCR10 is a novel CC chemokine receptor with a unique expression pattern that would be consistent with a role in placental immunity or hematopoiesis.

Molecular cloning and expression of a novel rat CC-chemokine receptor (rCCR10rR) that binds MCP-1 and MIP-1beta with high affinity.

Chemokines stimulate the migration and activation of leukocytes to areas of inflammation or tissue damage by binding to specific seven-transmembrane G protein-coupled receptors. We report the cloning of a novel rat CC-chemokine receptor, the rat CCR10-related receptor (rCCR10rR), with 72% amino acid identity to the human CC-chemokine receptor CCR10 and 30%-35% amino acid identity to the known human CC-chemokine receptors CCR1, CCR2, CCR3, CCR4, and CCR5. Multiple tissue northern analysis indicates that rCCR10rR is expressed at a higher level in spleen than in the other tissues assayed. The CC-chemokines MIP-1beta and MCP-1 bind with highest affinity to rCCR10rR, with K(D) = 0.4 and 0.7 nM, respectively. The CC-chemokines RANTES and MIP-1alpha were poor competitors for MIP-1beta binding, with IC50 values of 150 nM and 86 nM, respectively, but the K(D) for RANTES binding was still in the nanamolar range (4.8 nM). These results indicate that rCCR10rR is a true member of the CC-chemokine receptor family and may be involved in eliciting the responses to the CC-chemokines MIP-1beta and MCP-1.

Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung.

G protein-coupled receptors transduce the signal of a wide variety of hormones, neurotransmitters, cytokines, and other molecules across the cell membrane to elicit the corresponding response inside the target cells. We describe in this paper the molecular cloning and tissue distribution of a novel rat G protein-coupled receptor, GPR41, with highest homology to the human orphan G protein-coupled receptor DRY12. A lower degree of homology was seen with the receptors for bradykinin, angiotensin, and IL8. The expression of GPR41 appears to be the highest in brain and lung tissues, with lesser expression in heart, skeletal muscle, and kidney, as assayed by northern blotting. No GPR41 message was seen in spleen, liver, or testes. GPR41 failed to bind any of the ligands tested.

Estudio clínico de eficacia y tolerancia con sultamicilina fipexiam en procesos infecciosos de tratamiento ambulatorio / Clinic study of efficacy and toleration with sultamicilina fipeham in infectious process of ambulatory treatment

Se realizó un estudio abierto, multicéntrico, no comparativo donde se avaluó la eficacia y tolerancia de la combinación Ampicilina/Sulbatam por vía oral-Sultamicilina-(Fipexiam), en adultos y niños con infecciones del tracto respiratorio superior e inferior y con infeciones de piel y partes blandas, y adultos con Enfermedad Inflamatoria Pélvica (EIP). El estudio reunió los investigadores de 73 Centros. Se trataron un total de 195 pacientes obteniéndose una efectividad global de 93.3 por ciento. De estos pacientes 84 presentaron Otitis media aguda, resultando curas clínicas en el 89.2 por ciento, 67 presentaron procesos orofaríngeos con curación en el 94 por ciento; en los casos con infecciones de piel y partes blandas, así como en las mujeres tratadas con (EIP) la curación clínica fue de 100 por ciento. Se reportaron efectos adversos en 10.9 por ciento, siendo las molestias gastrointestinales más resaltantes con 8.7 por ciento de los casos reportados, siendo menores a lo reportado por la literatura médica

Compensatory alterations for insulin signal transduction and glucose transport in insulin-resistant diabetes.

Insulin binding activates the receptor tyrosine kinase toward the insulin receptor substrate-1 (IRS-1). Phosphorylated IRS-1 then interacts with the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K), Nck, growth factor receptor-bound protein 2 (GRB2), and Syp, thus branching insulin's signal for both mitogenic and metabolic responses. To determine whether the expression of these proteins is altered in insulin resistance, the levels of these proteins were compared in adipose and liver tissues of nondiabetic mice and obese insulin-resistant diabetic KKAy mice. IR and PI3K p85 alpha protein levels were significantly lower in KKAy mice than in control nondiabetic mice, whereas IRS-1 protein levels were not altered. In contrast, the protein levels of GRB2, Nck, Syp, and GLUT-1 were dramatically elevated in KKAy fat, with less striking changes in liver. Treatment of diabetic animals with pioglitazone, an insulin-sensitizing antihyperglycemic agent, partially corrected the expression of some of these proteins. Taken together, these findings suggest that the insulin-resistant diabetic condition is characterized by changes in expression of insulin signal transduction components that may be associated with altered glucose metabolism.

Altered expression of insulin signaling components in streptozotocin-treated rats.

Insulin signaling is known to proceed through the insulin receptor to the insulin receptor substrate-1 (IRS-1). Tyrosine-phosphorylation of IRS-1 causes it to associate with the src-homology-2 (SH2) domains of at least four other proteins: phosphatidylinositol 3'-kinase (PI3K), growth factor receptor-bound protein-2 (GRB2), Nck, and Syp. In order to understand the cellular derangements associated with type I diabetes, the levels of these four SH2-containing proteins was determined in streptozotocin-induced diabetic rats. In liver tissue of diabetic rats, the levels of Nck and Syp were significantly decreased to 71 +/- 6% and 61 +/- 4% control, respectively, while in fat tissue only the Syp levels were significantly reduced to 72 +/- 9% control. PI3K levels were higher in livers of diabetic rats than controls, but unchanged in fat. The insulin-deficient diabetic condition was thus associated with altered levels of insulin signaling components.

A rapid, accurate, nonradioactive method for quantitating RNA on agarose gels.

In order to study quantitative gene expression with Northern blots, it is important to have an internal standard that can be used to verify even loading or to correct for uneven loading between lanes. In this study it is shown that two-dimensional quantitation of ethidium bromide-intercalated 28S rRNA fluorescence can be used for such standardization. It was found that the film response of the fluorescence was linear with respect to total loaded RNA in the range of 2.5-12.5 micrograms RNA under the conditions used, after which the linear relationship falls off. This method eliminates the use of radiation for internal standardization of Northern blots.

Valores de osmolalidad serica en los recien nacidos normales a termino y pre-termino. / The values of the serum osmolarity in the normal term and preterm newborn infants

Se estudiaron 100 recien nacidos normales con sus respectivas madres sanas, cuyos nacimientos ocurrio en el Hospital Universitario de Los Andes, de la ciudad de Merida, durante un periodo de tres meses, y de los cuales fueron divididos en grupos de termino (n=80), y de pre-termino (n= 20). A las madres de estos recien nacidos, se les determino la osmolalidad serica medida por el descenso del punto crioscopico, durante el periodo expulsivo, y a los recien nacidos, se les determino la misma osmolalidad serica y los niveles de urea, glicemia y sodio serico, para obtener ademas-la osmolalidad serica calculada. El promedio de osmolalidad serica medida, para los 100 recien nacidos fue de 283 mOsm./Kg., no encontrandose diferencia estadisticamente significativa entre ambos grupos de neonatos. Ademas, se encontro buena correlacion entre la osmolalidad serica medida de los recien nacidos y los valores de osmolalidad serica de las madres. Existiendo una diferencia de 7 - 10 mOsm./Kg., entre la osmolalidad serica medida y la calculada. Otro de los hallazgos encontrados, es la correlacion existente entre la osmolalidad serica de los recien nacidos y sus niveles de sodio serico