Reproductive hormones modulate oxidative stress in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by gradual cognitive decline, impairments in speech and language, and dysfunction in the sensorimotor systems, culminating in complete reliance on nursing care. Oxidative stress, caused by an imbalance in the pro-oxidant/antioxidant mechanisms in the body, has been implicated in AD pathogenesis, as in many other age-associated diseases such as atherosclerosis, Parkinson disease, and amyotrophic lateral sclerosis. Although the hormones estrogen, progesterone, testosterone, and luteinizing hormone are best known for their roles in reproduction, many studies show these hormones have other roles, including neuroprotection. Changes in the levels of these hormones that occur in reproductive senescence are hypothesized to increase risk of AD, as a result of reduced protection against oxidative insults. The Abeta peptide, overproduction of which is thought to be a key pathogenic event in the development of AD, is neurotoxic, most likely due to its ability to promote oxidative stress. The reproductive hormones are known to influence Abeta metabolism, and this review discusses the beneficial and detrimental effects these hormones have on Abeta production and oxidative stress, and their relevance in potential AD therapies.     

Endogenous polyamines modulate Ca2+ channel activity in guinea-pig intestinal smooth muscle

The polyamines spermine and spermidine inhibit L-type Ca2+ channels in whole-cell recordings from guinea-pig ileum cells (Gomez and Hellstrand, Pflügers Arch, 430:501-507, 1995 [4]). To study whether they modulate channel activity under physiological conditions, we further investigated their actions on Ca2+ channels and the effects of altered cellular polyamine contents. In inside-out patches, spermine (0.1-1 mM) inhibited channel activity without affecting the amplitude of unitary currents. In cell-attached recordings, addition of spermine to the bath did not influence channel activity in the patch, indicating that its extracellular action is direct and not mediated via passage of the polyamine through the cell membrane. Cellular contents of spermidine and spermine were decreased by about 50% by organ culture of ileum strips for 5 days with the adenosylmethionine decarboxylase inhibitor CGP 48664 (10 microM). This caused enhanced channel activity in cell-attached recordings, suggesting a reduced level of channel block by endogenous polyamines compared with control cells. Whole-cell recordings in the perforated patch mode showed increased current in polyamine-depleted cells, while this was not seen when cells were dialysed with the pipette solution. We conclude that polyamines block Ca2+ channels from the inside as well as the outside of the cell membrane, and that endogenous polyamines in smooth muscle modulate Ca2+ channel activity.     

SORL1 haplotypes modulate risk of Alzheimer's disease in Chinese

Genetic variants of the neuronal sortilin-related receptor (SORL1) have been demonstrated to modulate the risk of Alzheimer's disease (AD) in different American and European populations [Rogaeva, E., Meng, Y., Lee, J.H., Gu, Y., Kawarai, T., Zou, F., Katayama, T., Baldwin, C.T., Cheng, R., Hasegawa, H., Chen, F., Shibata, N., Lunetta, K.L., Pardossi-Piquard, R., Bohm, C., Wakutani, Y., Cupples, L.A., Cuenco, K.T., Green, R.C., Pinessi, L., Rainero, I., Sorbi, S., Bruni, A., Duara, R., Friedland, R.P., Inzelberg, R., Hampe, W., Bujo, H., Song, Y.Q., Andersen, O.M., Willnow, T.E., Graff-Radford, N., Petersen, R.C., Dickson, D., Der, S.D., Fraser, P.E., Schmitt-Ulms, G., Younkin, S., Mayeux, R., Farrer, L.A., St George-Hyslop, P., 2007. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat. Genet. 39 (2), 168-177]. We conducted haloptype analysis involving two genetic clusters of SORL1 in AD and controls among Han Chinese. rs3824968 (SNP 23) was associated with an increased risk of AD, and there was a trend towards association for rs1699102 (SNP 22) and rs2282649 (SNP 24). More robust associations were found for three-loci haplotypes. In particular, the GCA haplotype at SNPs 19-22-23 was associated with an increased risk (odds ratio 1.4), and CTC haplotype at SNPs 19-22-23 and TCT at SNPs 22-23-24 a decreased risk (odds ratio 0.67) of AD. The complete absence of some at-risk North European haplotypes in our Chinese study subjects was likely due to different ancestral origins, with allelic heterogeneity among races. However, our study suggests that certain SORL1 haplotypes at SNPs 19-24 modulated risk of AD in our Chinese population.     

On the recall of vestibular sensations

Functional neuroimaging studies on the recall or imagination of a distinctive task in the motor network or of sensations in sensory systems (visual, acoustic, nociceptive, gustatory, and olfactory) demonstrated that the respective primary cortex is often involved in the mental imagery process. Our aim was to examine this phenomenon in the vestibular system using fMRI. Sixteen healthy subjects were asked to remember the feeling of a rotatory chair procedure in contrast to an identical situation at rest. Shortly afterwards they were asked to recall the vestibular experience in a 1.5-T scanner. The resulting activations were then compared with the responses of a galvanic vestibular control experiment and a rest condition. The vestibular recall showed significant bihemispheric activations in the inferior frontal gyri, the anterior operculum, the middle cingulate, the putamen, the globus pallidus, the premotor motor cortex, and the anterior insula. We found activations in regions known to play a role in spatial referencing, motor programs, and attention in the recall of vestibular sensations. But important known relay stations for the cortical processing of vestibular information showed neither relevant activations nor deactivations.     

Dietary oils modulate T-cell differentiation and IL-2 bioactivity of intestinal mucosal lymphocytes in chickens

The study was conducted to investigate the effects of dietary oils on the differentiation of intestinal lymphocytes and cytokines generation in chickens. One hundred and eighty chickens were assigned to three groups in one factorial design. Factor was dietary fat types (4.5% poultry oil, 4.5% corn oil or 4.5% fish oil). The proportion of CD3⁺CD4⁺ lymphocytes of intestinal mucosal lymphocytes (IMLs) in chickens fed fish-oil diets on 21 d and 42 d of age was significantly higher than those in chickens fed corn-oil and poultry-oil diets (P <0.01). And the proportion of intestinal CD3⁺CD8⁺ lymphocytes of chickens fed fish-oil diets was significantly lower than those of chickens fed corn-oil and poultry-oil diets (P <0.01) on 21 d and 42 d of age. Fish-oil consumption enhanced IL-2 secretion of IMLs stimulated with concanavalin A (ConA) (P <0.01), compared with poultry oil; but corn-oil consumption decreased IL-2 secretion than poultry-oil diets (P <0.01). Fish oil decreased the mRNA abundance of calcitonin gene-related peptide (cGRP) in intestinal mucosa of chickens on 21 d and 42 d of age compared to poultry oil (P <0.01). Corn oil increased the mRNA abundance of cGRP compared to poultry oil (P <0.01). Compared with group fed corn-oil or poultry-oil diets, IMLs had lower concentration of cAMP and lower bioactivity of adenylyl cyclase (AC) of chickens supplemented with fish oil on 21 d and 42 d of age. Meanwhile, corn oil increased cAMP level and AC bioactivity. Taken together, these data show a modulatory role for cGRP in the interaction between different type of oils and T-cell differentiation and IL-2 bioactivity of IMLs in chickens, which suggests that AC and cAMP signalling involved the intestinal mucosal immune responses.     

BRCA1 may modulate neuronal cell cycle re-entry in Alzheimer disease

In Alzheimer disease, neuronal degeneration and the presence of neurofibrillary tangles correlate with the severity of cognitive decline. Neurofibrillary tangles contain the antigenic profile of many cell cycle markers, reflecting a re-entry into the cell cycle by affected neurons. However, while such a cell cycle re-entry phenotype is an early and consistent feature of Alzheimer disease, the mechanisms responsible for neuronal cell cycle are unclear. In this regard, given that a dysregulated cell cycle is a characteristic of cancer, we speculated that alterations in oncogenic proteins may play a role in neurodegeneration. To this end, in this study, we examined brain tissue from cases of Alzheimer disease for the presence of BRCA1, a known regulator of cell cycle, and found intense and specific localization of BRCA1 to neurofibrillary tangles, a hallmark lesion of the disease. Analysis of clinically normal aged brain tissue revealed systematically less BRCA1, and surprisingly in many cases with apparent phosphorylated tau-positive neurofibrillary tangles, BRCA1 was absent, yet BRCA1 was present in all cases of Alzheimer disease. These findings not only further define the cell cycle reentry phenotype in Alzheimer disease but also indicate that the neurofibrillary tangles which define Alzheimer disease may have a different genesis from the neurofibrillary tangles of normal aging.     

Helicobacter pylori and gastric cancer: factors that modulate disease risk

Helicobacter pylori is a gastric pathogen that colonizes approximately 50% of the world's population. Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection with H. pylori is the strongest known risk factor for gastric cancer, which is the second leading cause of cancer-related deaths worldwide. Once H. pylori colonizes the gastric environment, it persists for the lifetime of the host, suggesting that the host immune response is ineffective in clearing this bacterium. In this review, we discuss the host immune response and examine other host factors that increase the pathogenic potential of this bacterium, including host polymorphisms, alterations to the apical-junctional complex, and the effects of environmental factors. In addition to host effects and responses, H. pylori strains are genetically diverse. We discuss the main virulence determinants in H. pylori strains and the correlation between these and the diverse clinical outcomes following H. pylori infection. Since H. pylori inhibits the gastric epithelium of half of the world, it is crucial that we continue to gain understanding of host and microbial factors that increase the risk of developing more severe clinical outcomes.     

Research progress on the relationship between intestinal microecology and intestinal bowel disease

Intestinal microecology is the main component of human microecology. Intestinal microecology consists of intestinal microbiota, intestinal epithelial cells, and intestinal mucosal immune system. These components are interdependent and establish a complex interaction network that restricts each other. According to the impact on the human body, there are three categories of symbiotic bacteria, opportunistic pathogens, and pathogenic bacteria. The intestinal microecology participates in digestion and absorption, and material metabolism, and inhibits the growth of pathogenic microorganisms. It also acts as the body''s natural immune barrier, regulates the innate immunity of the intestine, controls the mucosal barrier function, and also participates in the intestinal epithelial cells'' physiological activities such as hyperplasia or apoptosis. When the steady‐state balance of the intestinal microecology is disturbed, the existing core intestinal microbiota network changes and leads to obesity, diabetes, and many other diseases, especially irritable bowel syndrome, inflammatory bowel disease (IBD), and colorectal malignancy. Intestinal diseases, including tumors, are particularly closely related to intestinal microecology. This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis, treatment methods of IBD, and the changes in intestinal microbiota.     

Cool colors: color-induced nasal thermal sensations

We asked subjects to sniff a bottle containing distilled water and to say whether they felt a cooling or warming sensation in the nasal cavity. Odorless food coloring was added to three of these bottles so as to obtain one yellow, one green, one red and one colorless solution. Subjects were presented with each bottle four times under free viewing conditions or while blindfolded, and each nostril was tested separately. Although no thermal stimulus was present, subjects reported thermal sensations, but only under free viewing conditions. The nature of these sensations depended on the color of the solution, with green inducing cooling and red warming sensations. It also depended on which nostril was tested, with warming sensations evidenced only when the left nostril was tested, and cooling sensations only when the right nostril was tested. It is the first time color has been reported to induce nasal thermal sensations in the absence of thermal stimuli. These results are therefore entirely new. Furthermore, they suggest that thermosensory processing and judgment may depend on lateralized processes in the human brain.     

Ultrastructure of intestinal lymphatics in Crohn's disease

The fine structure of intestinal lymphatics in four patients with Crohn's disease and in two control subjects is described. Although obstructed lacteals are considered to be of major importance in the pathogenesis of regional enteritis, no detailed electron microscopic studies of lymphatic capillaries in this disease could be found. Even though both open and closed intercellular junctions were observed in the normal intestinal lymphatics, only closed junctions were noted in the mucosal and submucosal lymphatic capillaries in patients with regional enteritis. A heavy accumulation of protein rich lymph at the abluminal surface of lymphatic capillaries was consistently seen. None of the control lymphatics showed a similar alteration. The described fine structural changes indicate a decreased permeability of the lymphatic wall. Reduced lymphatic permeability could be a contributing element in the development of submucosal edema, a major microscopic feature of Crohn's disease.