Decline in hippocampal-dependent explicit memory (memory for facts and events) is one of the earliest clinical symptom of Alzheimer''s disease (AD). It is well established that synapse loss and ensuing neurodegeneration are the best predictors for memory impairments in AD. Latest studies have emphasized the neurotoxic role of soluble amyloid-beta oligomers (Aβo) that begin to accumulate in the human brain approximately 10 to 15 yr before the clinical symptoms become apparent. Many reports indicate that soluble Aβo correlate with memory deficits in AD models and humans. The Aβo-induced neurodegeneration observed in neuronal and brain slice cultures has been more challenging to reproduce in many animal models. The model of repeated Aβo infusions shown here overcome this issue and allow addressing two key domains for developing new disease modifying therapies: identify biological markers to diagnose early AD, and determine the molecular mechanisms underpinning Aβo-induced memory deficits at the onset of AD. Since soluble Aβo aggregate relatively fast into insoluble Aβ fibrils that correlate poorly with the clinical state of patients, soluble Aβo are prepared freshly and injected once per day during six days to produce marked cell death in the hippocampus. We used cannula specially design for simultaneous infusions of Aβo and continuous infusion of Aβo antibody (6E10) in the hippocampus using osmotic pumps. This innovative in vivo method can now be used in preclinical studies to validate the efficiency of new AD therapies that might prevent the deposition and neurotoxicity of Aβo in pre-dementia patients. 相似文献
Objective: To investigate clinical and imaging features of 40 patients with spontaneous intracranial hypotension (SIH).
Methods: 40 cases of spontaneous intracranial hypotension (SIH) diagnosed in our hospital from June 2013 to September 2017 were collected and retrospectively analyzed.
Results: In our study, the male to female ratio was 2:3. The average age of onset was 43.0?±?15.0?years. There were 12 (30.0%) patients with clear incentives, mostly catching cold. The average length of hospital stay was 11.2?±?6.3?days. All the patients showed orthostatic headaches, 62.5% patients with nausea or vomiting, 40.0% patients with neck stiffness, 17.5% patients with dizziness and vertigo, 10.0% patients with numbness and weakness of limbs, 5% patients with neck discomfort, and 2.5% patients with visual symptoms (visual impairment, photophobia, diplopia). 24 patients underwent CT scans which showed no abnormalities in 20 cases (83.3%), subdural fluid accumulation in 3 cases (12.5%), and subdural haematoma in 1 case (2.5%). Cranial contrast-enhanced MR scans showed diffuse pachymeningeal enhancement (95.83%, 23/24), signs of pituitary hyperaemia in 5 cases (20.8%), subdural fluid accumulation and subdural hematoma in 4 cases (16.7%), sagging of the brain in 3 cases (12.5%), and engorgement of venous structures in 1 case (4.1%). Six patients underwent plain and contrast-enhanced spinal MR scans which showed varying degrees of dural thickening and enhanced performance in all the patients. 92.5% (37/40) of patients had cerebrospinal fluid pressure <60 mmH2O on lumbar puncture. 97.5% of patients underwent conservative treatment with drugs and had a good outcome.
Conclusion: Orthostatic headache and cranial MRI diffuse pachymeningeal enhancement are characteristic features of SIH. Cranial contrast-enhanced MR scan is recognized as the first and non-invasive investigation in the diagnosis of SIH. Most patients had cerebrospinal fluid pressure <60 mmH2O. The vast majority of patients improved with fluid replacement. 相似文献
The effects of prolonged treatment with iron chelator (desferrioxamine) on the development of infection in mice inoculated with Y Trypanosoma cruzi were determined. Infected/treated mice presented lower levels of parasitemia and reduced mortality rate compared with infected/non-treated animals. The five out of twenty infected/treated mice that survived the acute phase of infection showed negative hemoculture and positive ELISA in the acute and chronic phases and positive PCR in the acute phase: in the chronic phase, three of the animals presented negative PCR. The single surviving infected/non-treated animal exhibited positive hemoculture, PCR and ELISA in both phases of infection. Infected groups presented lower levels of iron in the liver compared with treated/non-infected or non-treated/non-infected animals. The serum iron levels of the infected/non-treated group were higher on the 21st day post-infection in comparison with control and infected/treated groups. These results suggest that decrease of iron in the host leads to T. cruzi infection attenuation. 相似文献
Physically isolating organisms from disease agents should reduce the likelihood of disease transmission and infection, and
increase survival and growth, particularly in more vulnerable, early ontogenetic stages. During nest founding in fungus-growing
ants, foundresses of most genera use a garden platform to isolate the incipient fungal garden from the soil of the underground
chamber. We studied nest founding in Acromyrmex octospinosus to test the hypotheses that the use of a platform (rootlets used to suspend the fungus garden): (i) reduces the likelihood
that the garden will be contaminated by soil-borne microbial pathogens; (ii) results in more rapid growth of a young colony;
and (iii) increases colony survival. We manipulated natural incipient nests to have gardens either in contact with or isolated
from soil surrounding the chamber, and nests with and without foundresses present. We found a higher incidence of infection
in gardens that were in contact with the chamber soil and without queens, compared with gardens isolated from the chamber
soil with and without foundresses. The production of eggs, larvae and pupae, as well as leaf area harvested, were significantly
different between nests with and without platforms, but there were no differences in the production of workers nor garden
biomass. Likewise, there were no differences between treatments in colony survival rates over 8 weeks. Using smaller incipient
gardens, however, gardens with and without platforms differed in survivorship rates after 24 hours. The results indicate that
the use of a platform to cultivate an incipient fungal garden is an adaptation to reduce soil-borne diseases and increase
colony performance.
Received 28 July 2006; revised 15 November 2006; accepted 22 November 2006. 相似文献
It is well known that black and green tea extracts, particularly polyphenols, have antimicrobial activity against various pathogenic microbes including viruses. However, there is limited data on the antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged rapidly in China in late 2019 and which has been responsible for coronavirus disease 2019 (COVID-19) pandemic globally. In this study, 20 compounds and three extracts were obtained from black and green tea and found that three tea extracts showed significant antiviral activity against SARS-CoV-2, whereby the viral titre decreased about 5 logs TCID50 per ml by 1·375 mg ml−1 black tea extract and two-fold diluted tea bag infusion obtained from black tea when incubated at 25°C for 10 s. However, when concentrations of black and green tea extracts were equally adjusted to 344 µg ml−1, green tea extracts showed more antiviral activity against SARS-CoV-2. This simple and highly respected beverage may be a cheap and widely acceptable means to reduce SARS-CoV-2 viral burden in the mouth and upper gastrointestinal and respiratory tracts in developed as well as developing countries. 相似文献
Abstract: The regulation of 5-HT2A receptor expression by an antisense oligodeoxynucleotide, complementary to the coding region of rat 5-HT2A receptor mRNA, was examined in a cortically derived cell line and in rat brain. Treatment of A1A1 variant cells, which express the 5-HT2A receptor coupled to the stimulation of phosphatidylinositol (PI) hydrolysis, with antisense oligodeoxynucleotide decreased the maximal stimulation of PI hydrolysis by the partial agonist quipazine and the number of 5-HT2A receptor sites as measured by the binding of 2-[125I]-iodolysergic acid diethylamide. Treatment of cells with random, sense, or mismatch oligodeoxynucleotide did not alter the stimulation of PI hydrolysis by quipazine or 5-HT2A receptor number. Intracerebroventricular infusion of antisense, but not mismatch, oligodeoxynucleotide for 8 days resulted in a significant increase in cortical 5-HT2A receptor density and an increase in headshake behavior induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. The density of cortical 5-HT2A receptors was not altered by administration of antisense oligodeoxynucleotide for 1, 2, or 4 days. We hypothesize that in brain this antisense oligodeoxynucleotide relieved some form of translational suppression, resulting in an increase in 5-HT2A receptor expression. 相似文献