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1.
Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice 总被引:4,自引:0,他引:4
Sadowski M Pankiewicz J Scholtzova H Ji Y Quartermain D Jensen CH Duff K Nixon RA Gruen RJ Wisniewski T 《Journal of neuropathology and experimental neurology》2004,63(5):418-428
In Alzheimer disease (AD) patients, early memory dysfunction is associated with glucose hypometabolism and neuronal loss in the hippocampus. Double transgenic (Tg) mice co-expressing the M146L presenilin 1 (PS1) and K670N/M671L, the double "Swedish" amyloid precursor protein (APP) mutations, are a model of AD amyloid-beta deposition (Abeta) that exhibits earlier and more profound impairments of working memory and learning than single APP mutant mice. In this study we compared performance on spatial memory tests, regional glucose metabolism, Abeta deposition, and neuronal loss in APP/PS1, PS1, and non-Tg (nTg) mice. At the age of 2 months no significant morphological and metabolic differences were detected between 3 studied genotypes. By 8 months, however, APP/PS1 mice developed selective impairment of spatial memory, which was significantly worse at 22 months and was accompanied by reduced glucose utilization in the hippocampus and a 35.8% dropout of neurons in the CA1 region. PS1 mice exhibited a similar degree of neuronal loss in CA1 but minimal memory deficit and no impairment of glucose utilization compared to nTg mice. Deficits in 22 month APP/PS1 mice were accompanied by a substantially elevated Abeta load, which rose from 2.5% +/- 0.4% at 8 months to 17.4% +/- 4.6%. These findings implicate Abeta or APP in the behavioral and metabolic impairments in APP/PS1 mice and the failure to compensate functionally for PS1-related hippocampal cell loss. 相似文献
2.
Jana Jure
ekov Monika Kmeov Sivoov Henrieta Drobkov Mrk Híve Daniel Evin Jn Kliment Duan Dobrota 《Oncology Letters》2021,21(3)
Sex steroid hormones have important roles in the function of the prostate; however, they may also serve as factors in the initiation and progression of carcinogenesis. Estrogens, acting through estrogen receptors, may significantly affect prostate cancer development and progression. The main aim of the present study was to analyze the association between the rs3020449, rs4986938 and rs1256049 polymorphisms in the promoter region of the estrogen receptor β (ESR2) gene and prostate cancer risk in the Slovak population. A total of 510 patients with prostate cancer and 184 healthy men were included in the present study. No association between the rs4986938 and rs1256049 polymorphisms and prostate cancer development and progression was revealed; however, there was a statistically significant association between the rs3020449 GG genotype [odds ratio (OR), 2.35; P=0.002] and the G allele (OR, 1.42; P=0.005) and a higher risk of prostate cancer development. The rs3020449 GG genotype was significantly associated with a higher risk of development of carcinoma with a Gleason score >7 (OR, 2.66; P=0.005), as well as with the development of carcinoma with pT3/pT4 (OR, 2.28; P=0.02). According to the results from the present study, the rs3020449 polymorphism, in the promoter region of ESR2, may be considered to have a role in the development and progression of prostate cancer in the Slovak population. 相似文献
3.
Murajda L Sulaj M Hudecková H Litvová S Buchancová J 《Central European journal of public health》2010,18(3):173-176
We analyzed the occurrence of healthcare-associated infections (HAl) at intensive care unit of the Department of Anesthesiology and Intensive Medicine of Martin Faculty Hospital in 2008. We performed a retrospective-prospective observation according the protocol of European HELICS (Hospital in Europe Link for Infection Control and Surveillance) system. We found 11 HAl (4.45%) which on average prolonged the length of hospitalization by 6 days. The most frequent localisation of HAl was the respiratory tract. By our own observation we found the same number of HAl cases as it had been reported officially but the observed and reported cases do not match. The surveillance system HELICS uses definitions slightly different from those used in Slovakia. The severity of health status of a patient at admission influences the risk of HAl. We suggest a continuing collaboration on HELICS system with further involvement of all departments of Martin Faculty Hospital and creation of a hospital infection control team. We also suggest an improvement in testing for etiologic agents of HAl and an introduction of methods of molecular epidemiology in diagnostics, as well as quantification of costs related to occurrence of HAl and to assess an implication of automated monitoring system in HAl surveillance. 相似文献
4.
5.
Cristiano Scottà Giorgia Fanelli Sec Julie Hoong Marco Romano Estefania Nova Lamperti Mitalee Sukthankar Giuliana Guggino Henrieta Fazekasova Kulachelvy Ratnasothy Pablo D. Becker Behdad Afzali Robert I. Lechler Giovanna Lombardi 《Haematologica》2016,101(1):91-100
Immunosuppressive drugs in clinical transplantation are necessary to inhibit the immune response to donor antigens. Although they are effective in controlling acute rejection, they do not prevent long-term transplant loss from chronic rejection. In addition, immunosuppressive drugs have adverse side effects, including increased rate of infections and malignancies. Adoptive cell therapy with human Tregs represents a promising strategy for the induction of transplantation tolerance. Phase I/II clinical trials in transplanted patients are already underway, involving the infusion of Tregs alongside concurrent immunosuppressive drugs. However, it remains to be determined whether the presence of immunosuppressive drugs negatively impacts Treg function and stability. We tested in vitro and in vivo the effects of tacrolimus, mycophenolate and methylprednisolone (major ISDs used in transplantation) on ex vivo expanded, rapamycin-treated human Tregs. The in vitro results showed that these drugs had no effect on phenotype, function and stability of Tregs, although tacrolimus affected the expression of chemokine receptors and IL-10 production. However, viability and proliferative capacity were reduced in a dose-dependent manner by all the three drugs. The in vivo experiments using a humanized mouse model confirmed the in vitro results. However, treatment of mice with only rapamycin maintained the viability, function and proliferative ability of adoptively transferred Tregs. Taken together, our results suggest that the key functions of ex vivo expanded Tregs are not affected by a concurrent immunosuppressive therapy. However, the choice of the drug combination and their timing and dosing should be considered as an essential component to induce and maintain tolerance by Treg. 相似文献
6.
ABSTRACTMotherhood can be very challenging and overwhelming whether the individuals involved are teens or adults. Although there is a high prevalence of teenage mothers in urban cities in Ghana, little research has been done on the challenges associated with teen motherhood. This qualitative study was therefore conducted to explore the challenges that teenage mothers experience in Ghana. One-on-one interviews were conducted with 28 purposively selected teenage mothers between the ages of 15 and 19. Through thematic analysis, findings showed that challenges associated with teenage motherhood were strained interpersonal relationships, survival difficulties, educational disruption and steep transition to adulthood. These findings call for supportive programmes and interventions that would help address the contextual challenges of teenage mothers and also step up efforts to decrease the prevalence of teenage pregnancy in Ghana. 相似文献
7.
Scholtzova H Wadghiri YZ Douadi M Sigurdsson EM Li YS Quartermain D Banerjee P Wisniewski T 《Journal of neuroscience research》2008,86(12):2784-2791
Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to improve learning and memory in several preclinical models of Alzheimer's disease (AD). Memantine has also been shown to reduce the levels of amyloid beta (A beta) peptides in human neuroblastoma cells as well as to inhibit A beta oligomer-induced synaptic loss. In this study, we assessed whether NMDA receptor inhibition by memantine in transgenic mice expressing human amyloid-beta precursor protein (APP) and presenilin 1 (PS1) is associated with cognitive benefit and amyloid burden reduction by using object recognition, micromagnetic resonance imaging (micro MRI), and histology. APP/PS1 Tg mice were treated either with memantine or with vehicle for a period of 4 months starting at 3 months of age. After treatment, the mice were subjected to an object recognition test and analyzed by ex vivo micro MRI, and histological examination of amyloid burden. micro MRI was performed following injection with gadolinium-DTPA-A beta(1-40). We found that memantine-treated Tg mice performed the same as wild-type control mice, whereas the performance of vehicle-treated Tg mice was significantly impaired (P = 0.0081, one-way ANOVA). Compared with vehicle-treated animals, memantine-treated Tg mice had a reduced plaque burden, as determined both histologically and by micro MRI. This reduction in amyloid burden correlates with an improvement in cognitive performance. Thus, our findings provide further evidence of the potential role of NMDA receptor antagonists in ameliorating AD-related pathology. In addition, our study shows, for the first time, the utility of micro MRI in conjunction with gadolinium-labeled A beta labeling agents to monitor the therapeutic response to amyloid-reducing agents. 相似文献
8.
A synthetic peptide blocking the apolipoprotein E/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice
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Sadowski M Pankiewicz J Scholtzova H Ripellino JA Li Y Schmidt SD Mathews PM Fryer JD Holtzman DM Sigurdsson EM Wisniewski T 《The American journal of pathology》2004,165(3):937-948
Alzheimer's disease (AD) is associated with accumulation of beta-amyloid (Abeta). A major genetic risk factor for sporadic AD is inheritance of the apolipoprotein (apo) E4 allele. ApoE can act as a pathological chaperone of Abeta, promoting its conformational transformation from soluble Abeta into toxic aggregates. We determined if blocking the apoE/Abeta interaction reduces Abeta load in transgenic (Tg) AD mice. The binding site of apoE on Abeta corresponds to residues 12 to 28. To block binding, we synthesized a peptide containing these residues, but substituted valine at position 18 to proline (Abeta12-28P). This changed the peptide's properties, making it non-fibrillogenic and non-toxic. Abeta12-28P competitively blocks binding of full-length Abeta to apoE (IC50 = 36.7 nmol). Furthermore, Abeta12-28P reduces Abeta fibrillogenesis in the presence of apoE, and Abeta/apoE toxicity in cell culture. Abeta12-28P is blood-brain barrier-permeable and in AD Tg mice inhibits Abeta deposition. Tg mice treated with Abeta12-28P for 1 month had a 63.3% reduction in Abeta load in the cortex (P = 0.0043) and a 59.5% (P = 0.0087) reduction in the hippocampus comparing to age-matched control Tg mice. Antibodies against Abeta were not detected in sera of treated mice; therefore the observed therapeutic effect of Abeta12-28P cannot be attributed to an antibody clearance response. Our experiments demonstrate that compounds blocking the interaction between Abeta and its pathological chaperones may be beneficial for treatment of beta-amyloid deposition in AD. 相似文献
9.
Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging. 总被引:4,自引:0,他引:4
Youssef Zaim Wadghiri Einar M Sigurdsson Marcin Sadowski James I Elliott Yongsheng Li Henrieta Scholtzova Cheuk Ying Tang Gilbert Aguinaldo Miguel Pappolla Karen Duff Thomas Wisniewski Daniel H Turnbull 《Magnetic resonance in medicine》2003,50(2):293-302
The presence of amyloid-beta (Abeta) plaques in the brain is a hallmark pathological feature of Alzheimer's disease (AD). Transgenic mice overexpressing mutant amyloid precursor protein (APP), or both mutant APP and presenilin-1 (APP/PS1), develop Abeta plaques similar to those in AD patients, and have been proposed as animal models in which to test experimental therapeutic approaches for the clearance of Abeta. However, at present there is no in vivo whole-brain imaging method to detect Abeta plaques in mice or men. A novel method is presented to detect Abeta plaques in the brains of transgenic mice by magnetic resonance microimaging (muMRI). This method uses Abeta1-40 peptide, known for its high binding affinity to Abeta, magnetically labeled with either gadolinium (Gd) or monocrystalline iron oxide nanoparticles (MION). Intraarterial injection of magnetically labeled Abeta1-40, with mannitol to transiently open the blood-brain barrier (BBB), enabled the detection of many Abeta plaques. Furthermore, the numerical density of Abeta plaques detected by muMRI and by immunohistochemistry showed excellent correlation. This approach provides an in vivo method to detect Abeta in AD transgenic mice, and suggests that diagnostic MRI methods to detect Abeta in AD patients may ultimately be feasible. 相似文献
10.
Behdad Afzali Francis C. Edozie Henrieta Fazekasova Cristiano Scottà Peter J. Mitchell James B. Canavan Shahram Y. Kordasti Prabhjoat S. Chana Richard Ellis Graham M. Lord Susan John Rachel Hilton Robert I. Lechler Giovanna Lombardi 《Clinical journal of the American Society of Nephrology》2013,8(8):1396-1405