Percutaneous endoscopic gastrotomy: better than nasoenteric tube?
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Biomedical subjects
Publications and source records attributed to C Fernández-Viadero.
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The low density lipoprotein receptor-related protein (LRP) may influence both the clearance and the production of beta-amyloid peptide and thus plays a role in Alzheimer's disease (AD) pathogenesis. Previous studies, although inconsistent, have suggested that the LRP exon 3 CC genotype contributes to the risk of AD. A case-control study utilizing a clinically well-defined group of 305 sporadic AD patients and 304 control subjects was performed to test this association in an ethnically homogeneous population from Spain. In the current study, the LRP CC genotype was not over-represented in AD patients compared to non-demented controls. A meta-analysis of previous studies revealed a weak correlation of LRP CC genotype with AD (odds ratio of 1.35, P=0.01).
An association between cognitive performance in elderly people and variability in the codon 129 of the prion protein gene (PRNP) has been recently described. The authors analyzed this polymorphism in 278 sporadic AD patients and 268 cognitively normal control subjects. Analyses stratifying by APOE genotype, age, and gender failed to reveal any association between homozygosity for the 129 PRNP methionine or valine alleles and AD.
INTRODUCTION: Recent reports indicate that the K variant of the butyrylcholinesterase (BCHE) gene may act in synergism with the epsilon4 allele of apolipoprotein E (APOE) to increase the risk of Alzheimer's disease (AD), but this is controversial. MATERIAL AND METHODS: We genotyped for the BCHE-K and APOE epsilon4 alleles in a sample of 249 AD patients and 250 controls derived from the same region in a Spanish population. RESULTS: A protective effect of the K variant of BCHE with an odds ratio of 0.41 (95% confidence interval 0.19-0.86, P=0.02) was observed among non-APOE epsilon4 carriers, but it was limited to women. CONCLUSION: Our study is the first to demonstrate that lower susceptibility to AD determined by the K variant of BCHE is dependent on gender.
We examined the possible involvement of polymorphisms of the presenilin 1 (PS1) and presenilin 2 (PS2) genes in the risk for sporadic Alzheimer's disease (AD), either through an independent effect or through interaction with the existing apolipoprotein E (ApoE) risk, in 211 AD cases and 188 age-matched control subjects. No significant differences were obtained in any of the comparisons relating the effect of the PS1 and PS2 polymorphisms; thus, these polymorphisms do not appear to be sufficient risk factors by themselves for sporadic AD. Although the ApoE varepsilon4 genotype is the only definite predictor of risk, homozygosity for either the 1 allele of the PS1 or the C allele of the PS2 genes may increase the risk conferred by the presence of an ApoE epsilon4 allele. Additionally, combination of PS1/11 and PS2/CC genotypes might have a small synergistic effect on the risk for AD.
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INTRODUCTION: The role of gender in Alzheimer's disease (AD), and its possible interaction with apolipoprotein E (apoE), has been controversial. MATERIAL AND METHODS: ApoE allelic frequencies and the effect of apoE epsilon4 allele dosage on risk and age at onset of AD were evaluated, separately for men and women, in 100 patients with sporadic AD and 100 age-matched controls. RESULTS: The distribution of apoE alleles and the odds ratio for AD, when associated with 1 or 2 epsilon4 alleles, were not statistically different between men and women. No effect of the dosage of the epsilon4 allele was found on the age at onset of dementia in the 2 sex groups. CONCLUSION: Our data suggest that the relation of the apoE genotype to AD is not dependent on sex.
Co-localization of calretinin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity was studied in the rat hippocampus and dentate gyrus. Neurons co-expressing both markers (CR/NADPH-d) were observed throughout the hippocampus and dentate gyrus. However, they were more abundant in the stratum pyramidale and radiatum of CA3, stratum pyramidale of CA1, and in the juxtagranular zone of the hilus. The NADPH-d activity appeared in 37% of the calretinin immunoreactive neurons in CA3, 42% in CA1, and 36% in the dentate gyrus, whereas calretinin immunoreactivity occurred in 41% of the NADPH-d positive neurons in the hippocampus, and 16% in the dentate gyrus. The morphology and location of the double marked cells could not be used as a characteristic of the co-localizing neurons. The heavily stained NADPH-d neurons occurring mainly in CA1 do not show calretinin immunoreactivity. NADPH-d fiber swellings could be observed in close apposition to calretinin immunoreactive neurons and dendrites, suggesting synaptic contacts. It has been reported that calretinin immunoreactivity and NADPH-d activity co-localize infrequently in other areas such as the neocortex, striatum, hypothalamus and tegmental nucleus. The relatively high proportion of double marked cells found in the hippocampus and dentate gyrus could be indicative of the importance of the CR/NADPH-d interneurons in the circuitries of these areas.
The effect of chronic intake of cytidine-5'-diphosphate choline (CDP choline), a precursor of the membrane lipid phosphatidylcholine, was analyzed in secretory cells of the Harderian gland (HG) of aged (26-month-old) female Swiss mice. These mice were treated with the drug from 12 months of age until they were 26 months old. The results obtained were compared with those of an age-matched control group and another adult (12-month-old) control group. In both control groups, the HGs displayed secretory tubules formed by a single squamous epithelium of lipid-secreting cells. The tubule lumens were occupied by numerous small pleomorphic porphyrin accretions. In contrast, the tubules of the CDP-choline-treated animals consisted of a single columnar epithelium, with lipid-secreting cells filled with lipid vacuoles. The most striking feature in the HGs of the CDP-choline group was the absence of prophyrin deposits. These observations indicate that porphyrin biosynthesis in female Swiss mice is maintained even in very old animals, and that chronic administration of CDP choline prevents porphyrin deposition in the HG of aged animals.
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Since melatonin has direct inhibitory effects on some tumor cells in vitro, the aim of the present work was to study whether the growth and structural characteristics of the human neuroblastoma cell line SK-N-SH in vitro are influenced by this indoleamine. Concentrations of melatonin of 10(-9) and 10(-11) M significantly inhibited (P < 0.05) cell proliferation. Subphysiological (10(-13) M) or supraphysiological (10(-7) and 10(-5) M) concentrations of melatonin lacked this effect. After 8 days of exposure to melatonin (10(-9) M), cells showed significantly smaller cell and nuclear sizes than control cells. Melatonin-treated cells presented greater neurite outgrowth than control cells. These results support the hypothesis that melatonin, at physiological concentrations, exerts a direct antiproliferative effect on SK-N-SH cells, promoting the differentiation of neuroblastoma cells.
The influence of chronic administration of cytidine-5'-diphosphate choline (CDP-choline), a precursor of the membrane lipid phosphatidylcholine, was studied in neurosecretory neurons (NSNs) of the supraoptic nucleus (SON) of aged mouse hypothalamus. Animals were treated with CDP-choline from 12 months of age until 26 months. They were studied for both morphologic and morphometric features. The results obtained were compared to those of an age-matched control group. There was evidence of differences between NSNs of the control group and those of the CDP-choline group which showed neuronal hypertrophy. This size increase was mainly attributed to the increment of cellular protein synthesis machinery, rough endoplasmic reticulum (RER) and Golgi complexes. Furthermore there was an increase in the number of neurosecretory granules (NSGs) in the CDP-choline group. In addition, there was no tertiary lysosomes in the treated animals. Moreover, the percentage of NSN membrane that was not covered by glial prolongations, increased from about 2% in the control group to 12% in the CDP-Choline treated group. These changes suggested an activation of the cellular processes for neurohormone synthesis in the experimental group. Furthermore, these NSNs displayed lipid droplets in their cytoplasm. The possible relationship between CDP-choline and NSNs activity is discussed.
We used differentiating chick and rat Purkinje cells to investigate in homologous neurons the influence of the number of nucleolar organizer regions (two in the chick and six in the rat) on the behaviour of the nucleolus and coiled bodies. We employed specific silver-staining methods on smear preparations and on semithin and ultrathin sections. In chick Purkinje cells the number of nucleolar silver-staining granules increased from 15.7 +/- 3 (mean +/- SD) at embryonic day 13 to 23.8 +/- 3 at post-hatching day 7. These nucleolar granules were unevenly distributed between the two nucleoli of binucleolated cells. Electron-microscopic cytochemistry showed that nucleolar granules are equivalent to the fibrillar centres with their associated shell of dense fibrillar component. A reduction in the number of nucleoli was found during the differentiation of both chick and rat Purkinje cells, although in mature cells the average number of nucleoli per cell was higher in the chick (1.60) than in the rat (1.07). The number of coiled bodies decreased from 1.33 in newborn rats to 0.47 at postnatal day 90 in the rat. Coiled bodies were not observed in homologous chick Purkinje cells. The dynamic behaviour of nucleoli and coiled bodies during neuronal differentiation and the relationship of these two nuclear organelles with the number of nucleolar organizer regions is discussed.
The effects of the retinal ganglion cell (RGC) activity blockage on the early myelination of the rat optic nerve (ON) were investigated at the light and ultrastructural levels. The blockage of the RGC action potential was attained by the use of tetrodotoxin (TTX), a blocker of the voltage-sensitive sodium channels. TTX was either infused directly into the left eye (TON) or injected systematically (SON). These two groups of ONs were compared with the untreated paired right nerves (UON) of the eye-infused group. Our observations showed that the general morphology of the ONs in either treated group was similar to that of the UONs. The most noticeable ultrastructural feature of these nerves was the presence of dimorphic myelin sheaths in 4% of the myelinated fibres (MFs) in the TON group at postnatal day twelve, while they were seldom observed in the other groups (0.5%). These abnormal covers were of two types; long flaps of aberrant myelin or redundant myelin profiles. However, at postnatal day seven, the onset of myelination and the percentage of MFs was similar in the three groups. The morphometric results showed that there were no age-group differences in axon size in unmyelinated and MFs. These results suggest that while the bioelectrical activity of the RGCs could not play any role in maintaining axon calibre it may, to some extent, regulate the process of formation of normal myelin sheaths in the rat ON.
In 2-year-old mice, astrocytes of the supraoptic nucleus (SON) of the hypothalamus, placed in close contact with the meningeal covering contained concentric arrangements of cisterns in their cytoplasm called glial concentric bodies (GCBs). They are formed by a variable number of flattened cisterns without pores, and no anastomosis was observed between adjacent cisterns. Rough endoplasmic reticulum (RER) cisterns do not show continuity with fully developed GCBs, although a close continuity between RER cisterns and GCBs was present in images suggesting GCB formation. Concomitantly with the appearance of GCBs, ventral neurosecretory neurons of the SON showed a cytoplasmic membrane reinforced by the apposition of glial prolongations. The possible origin and function of these GCBs and lamellae are discussed here.
Melatonin has been shown to have a direct inhibitory effect on the proliferation of estrogen-responsive MCF-7 human breast cancer cells, involving an interaction with estradiol. The anti-proliferative effect of melatonin is reversed by the addition of estradiol to the culture. In the present study, we examined whether inhibition by melatonin and subsequent estrogen rescue of MCF-7 cells are correlated with morphological and morphometric changes in these cells. After 4 days of exposure to melatonin, MCF-7 cells showed significantly smaller cell and nuclear sizes than other groups. These morphometric results were closely related to the ultrastructural features observed in these cells. While control and estradiol-treated cells showed increased tumor characteristics, melatonin-treated cells presented greater differentiation, in keeping with their epithelial origin (presence of cytokeratin filament bundles, conspicuous rough endoplasmic reticulum, and Golgi cisternae together with the presence of prominent nucleoli at the nuclear level). Additionally, some melatonin-treated cells displayed degenerative features (mitochondrial swelling with disruption of cristae, cytoplasmic vacuolation, nuclear chromatin disgregation and cell lysis). The addition of estradiol to cells previously incubated with melatonin reversed the changes induced by the latter and these cells showed the same ultrastructural features as the control cells. Our results support the notion that melatonin exerts its antitumor effect through a cell-cycle-specific mechanism by delaying the entry of MCF-7 cells into mitosis. This allows the tumor cells to achieve greater differentiation. The fact that the morphometric and morphological effects induced by melatonin are counteracted by estrogens suggests a cell-cycle acceleration induced by estradiol.
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