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At least 1,441 records · Page 80Linked to original sources
PubMed1987

Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases.

The status of cholinergic receptors in dementia is related to the question of potential cholinergic therapy. Whilst muscarinic receptor binding is generally reported to be normal or near normal, findings are reported which indicate substantial reductions of hippocampal nicotinic (high affinity nicotine) binding (occurring in conjunction with decreased choline acetyltransferase) in both Alzheimer's and Parkinson's but not Huntington's disease. A further indication that nicotinic receptor function may be abnormal in Alzheimer's disease is the extensive loss of an endogenous compound, detected for the first time in human brain, which inhibits normal nicotinic binding. Both receptor binding and the inhibitor are also substantially decreased with increasing age in the normal hippocampus.

Adult↗
PubMed1988

Somatostatin content and receptors in the cerebral cortex of depressed and control subjects.

Somatostatin-like immunoreactivity is reduced in the cerebrospinal fluid in depression and this is presumed to reflect alterations in cerebral somatostatinergic systems. We have examined this hypothesis by measuring this immunoreactivity and somatostatin receptors in post-mortem cortical tissue from depressed patients and control subjects. There was no significant difference in the temporal and occipital cortex in somatostatin-like immunoreactivity or in somatostatin receptor affinity and binding capacity between depressed and control groups. It is concluded that there may not be an alteration of cortical somatostatin function in depression.

Aged↗
PubMed1981

Total body potassium depletion and severe myopathy due to chronic liquorice ingestion.

A 33-year-old patient with hypokalaemia associated with severe myopathy following liquorice ingestion is described. Potassium depletion was confirmed by total body potassium measurements and myopathy was established by electromyography and enzyme studies. The potential hazard of chronic liquorice consumption even as a sweet is illustrated by this case.

Adult↗
PubMed1975

Dissolving foreign bodies in the trachea and bronchus.

Two young children inhaled sweets which dissolved in the tracheobronchial secretions and caused severe respiratory obstruction. The viscid fluid produced as the sweet dissolved was not expectorated and bronchoscopy was necessary. The oedema of the mucosa caused by the presence of a hyperosmolar sugar solution took up to 48 hours to resolve; antibiotics and steroid cover were considered necessary. The similarity of presentation with acute tracheobronchitis and the lack of reports in the literature suggest that such cases may be misdiagnosed.

Airway Obstruction↗
PubMed2005

Cingulate cortex: a closer look at its gut-related functional topography.

Earlier studies have documented activation of the cingulate cortex during gut related sensory-motor function. However, topography of the cingulate cortex in relationship to various levels of visceromotor sensory stimuli and gender is not completely elucidated. The aim was to characterize and compare the activation topography of the cingulate cortex in response to 1) subliminal, 2) perceived rectal distensions, and 3) external anal sphincter contraction (EASC) in males and females. We studied 18 healthy volunteers (ages 18-35 yr; 10 women, 8 men) using functional MRI blood-oxygenation-level-dependent technique. We obtained 11 axial slices (voxel vol. 2.5-6.0 x 2.5 x 2.5 mm(3)) through the cingulate cortex during barostat-controlled subliminal, liminal, and supraliminal nonpainful rectal distensions as well as EASC. Overall, for viscerosensation, the anterior cingulate cortex exhibited significantly more numbers of activated cortical voxels for all levels of stimulations compared with the posterior cingulate cortex (P < 0.05). In contrast, during EASC, activity in the posterior cingulate was larger than in the anterior cingulate cortex (P < 0.05). Cingulate activation was similar during EASC in males and females (P = 0.58), whereas there was a gender difference in anterior cingulate activation during liminal and supraliminal stimulations (P < 0.05). In females, viscerosensory cortical activity response was stimulus-intensity dependent. Intestinal viscerosensation and EASC induce different patterns of cingulate cortical activation. There may be gender differences in cingulate cortical activation during viscerosensation. In contrast to male subjects, females exhibit increased activity in response to liminal nonpainful stimulation compared with subliminal stimulation suggesting differences in cognition-related recruitment.

Adolescent↗
PubMed2003

Characterization of the cerebral cortical representation of heartburn in GERD patients.

Although symptoms arising from the esophagus such as heartburn and pain can at times become challenging clinical problems, esophageal viscerosensation, especially with regard to chemical stimulation in humans, is incompletely understood. Our aims were 1) to characterize and ascertain the reproducibility of cerebral cortical registration of heartburn and 2) to elucidate the differences between these findings and those of esophageal subliminal acid stimulation in asymptomatic controls. We studied 11 gastroesophageal reflux disease (GERD) patients (9 males, 30-55 yr) and 15 healthy controls (8 males, 21-49 yr). Cerebral cortical functional magnetic resonance imaging (fMRI) activity was recorded twice in each subject, during two 5-min intervals of 0.1 N HCl, separated by 5 min of NaCl perfusion. Time from onset of acid perfusion to instant of fMRI signal increase and first report of heartburn averaged 1.60 +/- 0.80 and 1.85 +/- 0.60 min, respectively. Average maximum percent signal increase in the GERD patients (16.3 +/- 3.5%) was significantly greater than that of healthy controls (3.8 +/- 0.9%; P < 0.01). Temporal fMRI signal characteristics during heartburn were significantly different from those of subliminal acid stimulation in controls (P < 0.01). Activated cortical regions included sensory/motor, parieto-occipital, cingulate and prefrontal regions, and the insula. There was 92% concordance between the activated Brodmann areas in repeated studies of GERD patients. Cortical activity associated with perceived and unperceived esophageal acid exposure in GERD patients and healthy controls, respectively, involves multiple brain regions but occurs more rapidly and with greater intensity in GERD patients than the activity in response to subliminal acid exposure in healthy controls. The cortical pain-processing pathway seems to be involved in perception of esophageal acid exposure and could explain the variations encountered in clinical practice defining this sensation.

Adult↗
PubMed2006

Effect of aging on bolus kinematics during the pharyngeal phase of swallowing.

Swallowing difficulty is a common complaint in the elderly and, although there are data for the biomechanics of liquid swallows, little is known about solid bolus motion, or kinematics, in the elderly. The aims of this study were as follows: 1) to characterize and compare solid and liquid bolus kinematics in the elderly and compare the findings with those in young subjects and 2) to correlate bolus kinematics and dynamics. Concurrent manometric-fluoroscopic techniques were used to study eight young and eight elderly subjects. The subjects performed four swallows each of 0.2-cm-diameter solid barium pellets and 5 ml of liquid barium during sagittal fluoroscopy and six-channel pharyngoesophageal manometry. Images were digitized for analysis of kinematic properties such as velocity and acceleration. Dynamic pressures were recorded and coordinated with kinematic events. Image analysis showed that velocity varied as the pellet passed through the hypopharynx, pharynx, and upper esophageal sphincter. In young subjects, pellet kinematics were characterized by two zones of pellet acceleration: one over the tongue base and another as the pellet passed through the upper esophageal sphincter. Although the elderly showed a similar zone of acceleration over the base of the tongue, the second zone of pellet acceleration was not seen. Decreasing pressure gradients immediately distal to the position of the solid pellet and liquid bolus characterized dynamics for all subjects. This decreasing pressure gradient was significantly larger in elderly than in young subjects. Bolus kinematics and dynamics were significantly altered among elderly compared with young subjects. Among these differences were the absence of hypopharyngeal bolus acceleration and a significant increase in the trans-sphincteric pressure gradient in the elderly.

Adolescent↗
PubMed2004

Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist.

Tumor-associated angiogenesis is critical for tumor growth and metastasis and is controlled by various pro- and antiangiogenic factors. The Eph family of receptor tyrosine kinases has emerged as one of the pivotal regulators of angiogenesis. Here we report that interfering with EphA signaling resulted in a pronounced inhibition of angiogenesis in ex vivo and in vivo model systems. Administration of EphA2/Fc soluble receptors inhibited, in a dose-dependent manner, microvessel formation in rat aortic ring assay, with inhibition reaching 76% at the highest dose of 5000 ng/ml. These results were further confirmed in vivo in a porcine aortic endothelial cell-vascular endothelial growth factor (VEGF)/basic fibroblast growth factor Matrigel plug assay, in which administration of EphA2/Fc soluble receptors resulted in 81% inhibition of neovascularization. The additive effects of simultaneous inhibition of VEGF receptor 2 and EphA signaling pathways in aortic ring assay and antiangiogenic efficacy of EphA2/Fc soluble receptors against VEGF/basic fibroblast growth factor-mediated neovascularization in vivo indicated a critical and nonredundant role for EphA signaling in angiogenesis. Furthermore, in two independent experiments, we demonstrated that EphA2/Fc soluble receptors strongly (by approximately 50% versus controls) suppressed growth of ASPC-1 human pancreatic tumor s.c. xenografts. Inhibition of tumor growth was due to decreased proliferation of tumor cells. In an orthotopic pancreatic ductal adenocarcinoma model in mice, suppression of EphA signaling by i.p. administration of EphA2/Fc (30 micro g/dose, three times a week for 56 days) profoundly inhibited the growth of primary tumors and the development of peritoneal, lymphatic, and hepatic metastases. These data demonstrate a critical role of EphA signaling in tumor growth and metastasis and provide a strong rationale for targeting EphA2 receptors for anticancer therapies.

Angiogenesis Inhibitors↗
PubMedDate not supplied

The influence of specific foods and oral hygiene on the microflora of fissures and smooth surfaces of molar teeth: A 5-day study.

A group of 20 students, harbouring >10(4) mutans streptococci per millilitre of saliva, was enrolled into the study. Models for sampling, reproducibly, the dental plaque present in specific sites (fissure and smooth surface) on the dentition were developed and validated. Withdrawal of normal oral hygiene procedures for only 1 day resulted in approximately 10-fold increases in the number of micro-organisms recovered from both sites. The effect of supplementing the subjects' diets with particular food items given 5 times per day [lemonade (5.8% w/v sugars, 250 ml), biscuits (digestive biscuits, 67.6% w/w carbohydrate of which 22% w/w was sugars and 45.6% w/w was starch), caramel toffees and sugar lumps] on the number of micro-organisms recovered and on the composition of the flora at both sites was determined. Dental plaque samples were taken after 5 days and it was found that supplementation of the diet with toffee and sugar lumps resulted in significantly more micro-organisms at both sampling sites. The supplementation of the diets with lemonade or biscuits did not significantly alter the numbers of micro-organisms recovered from either site. The percentage composition of the plaque samples from both dental sites remained relatively unaffected by oral hygiene although there were lower levels of mutans streptococci which might be related to the use of an antimicrobial toothpaste containing fluoride, triclosan and zinc citrate. This study suggests that the cariogenicity of certain sucrose-containing foods may, in part, be due to the enhancement of plaque accumulation in addition to other effects on the percentage composition of the plaque which may become manifest on prolonged usage of these dietary foodstuffs. These observations are consistent with dietary survey findings which often find consumption of confectionery related to caries experience or incidence.

Actinomyces↗
PubMed2000

Craving shift in chronic alcoholics.

In order to investigate changes in the consumption of substances that stimulate the reward system, 222 recently detoxified alcoholics were asked about their consumptional habits before as compared to after detoxification (mixed prospective and retrospective design). Seventy-eight point two percent reported an increase in consumption of coffee, cigarettes, chocolate and other sweets, while 34.9% managed to reduce at least one of these substances. The increase was significant for coffee, chocolate and other sweets. The desire for consumption of these substances was correlated with the maximum ever experienced desire for alcohol (0.232 for coffee, 0.213 for cigarettes, 0.193 for chocolate and 0.176 for other sweets), and the actual consumption of coffee, cigarettes and sweets was correlated with the actual desire for alcohol (0.172, 0.157 and 0.245, respectively). The results lend some support to the hypothesis that psychotropic substances might serve as a kind of self-regulation against craving in this group. A possible link to biochemical theories is discussed.

Adult↗
PubMedDate not supplied

Neuropathological diagnoses in elderly patients in Oslo: Alzheimer's disease, Lewy body disease, vascular lesions.

Neuropathological changes in elderly residents of Oslo, Norway were characterised with respect to the cerebral substrates of dementia. Ninety-two brains were examined, representing 41% of all deaths occurring in 10 nursing homes during a 9-month period. The autopsy cohort showed a similar mean age (85 years) and sex ratio (73% female) and proportion of demented patients (75%) compared to all the patients resident in these homes who died during the same period. Clinical data was compiled retrospectively. Diagnosis was made using the CERAD protocol, and criteria for the diagnosis of Lewy body dementia. Lewy body formation was present in 20% and cerebral infarction in 21% of patients. In the demented group (69 patients) 90% fulfilled CERAD criteria for definite or probable Alzheimer's disease. Eight demented cases had absent neocortical neurofibrillary tangles and 6 other cases showed Lewy body dementia (9% of demented patients). A further 8 of these demented cases had brain stem Lewy bodies with only minimal cortical involvement. Thirteen cases (19% of the sample) had cerebral infarcts but these were considered to be clinically significant in only 4 (6%). In the non-demented patients (23) 4 patients had brain stem Lewy bodies and 6 had cerebral infarcts. Despite inclusion criteria biased towards the collection of Alzheimer's disease and normal patients, both Lewy body dementia (7%) and cerebral infarcts contributing to dementia (6%) were frequent.

Aged↗
PubMed1992

Immunocytochemical localisation of transferrin in the human brain.

Immunocytochemical studies on the adult human brain have shown that transferrin is localized within three main compartments in the adult human brain. Oligodendrocytes and some astrocytes together with cells of the choroid plexus showed the highest intensity of staining. Neuronal staining occurred mainly within pyramidal or large polygonal cells, but this showed considerable regional variation being most marked in areas such as the cerebral cortex, amygdala, hippocampus, brainstem and cerebellar Purkinje cells. Small neurones such as caudate interneurones and granule cells showed relatively low activity. Diffuse immunostaining of the neuropil was evident, particularly where heavy neuronal or glial staining occurred. Immunostaining was also observed in white-matter fibre tracts. This pattern of distribution helps to provide a model for the mechanisms responsible for iron homeostasis in the normal brain.

Astrocytes↗
PubMed1992

Histochemical distribution of non-haem iron in the human brain.

The detailed anatomical distribution of iron in the post-mortem human brain has been studied using Perl's and Turnbull's methods with the diaminobenzidine intensification procedure for the demonstration of non-haem Fe3+ and Fe2+, respectively. Attention to methodological procedures has revealed that even brief immersion of tissue in routinely used fixatives causes a reduction of staining intensity in areas of high iron content and, often, loss of staining in areas of low iron content. Optimal staining is obtained using frozen section briefly fixed for 5 min in 4% formalin and Perl's stain (Fe3+) with diaminobenzidine intensification. Highest levels of stainable iron were found in the extrapyramidal system with the globus pallidus, substantia nigra zona reticulata, red nucleus and myelinated fibres of the putamen showing highest staining reactivity. Moderate staining intensity with Perl's technique was found in the majority of forebrain, midbrain and cerebellar structures with the striatum, thalamus, cortex and deep white matter, substantia nigra zona compacta, and cerebellar cortex showing consistent staining patterns with intensification of Perl's stain. The brain-stem and spinal cord generally only showed staining with the intensification procedure and even this was of low intensity. Microscopically the non-heam iron appears to be found predominantly in glial cells as fine cytoplasmic granules which in heavily stained areas coalesce to fill the entire cell. Iron-positive granules appear to be free in the neuropil and also around blood vessels in the globus pallidus, striatum and substantia nigra. The neuropil shows a fibrous impregnation when stained for iron which is, in part, derived from glial processes, myelinated fibres and fibre bundles. Neurones, in general, show only very low reactivity for iron, and this is difficult to discern due, often, to the higher reactivity of the surrounding neuropil. In the globus pallidus and substantia nigra zona reticulata, neurones with highly stainable iron content are found with granular cytoplasmic iron reactivity similar to that seen in the local glial cells. Our results are comparable with those of early workers, but with the use of intensification extend the distribution of non-haem iron to areas previously reported as negative. No apparent correlation of iron staining with known neurotransmitter systems is seen and the predilection for the extrapyramidal system is not easily explained, though the non-haem iron in the brain appears to be as a storage form in the iron storage protein ferritin. The localization of iron in the brain provides a foundation for the study of iron in certain neurodegenerative diseases such as Parkinson's disease, where iron has been implicated in the pathogenesis.

Aged↗