Several studies revealed that proteoglycans (PGs) and glycosaminoglycans (GAGs) play a pivotal role in the pathogenesis of Alzheimer's disease (AD). PGs have affinity to amyloid beta (Aβ) and protect ...it against proteolysis, and the consequent aggregation is the cause of neurotoxicity. This effect is believed to be attenuated by GAGs. Moreover, a low-molecular-weight GAG C3 derived from unfractionated heparin has been reported to protect against Aβ-induced tau-2 immunoreactivity and cholinergic damage induced by a cholinotoxin, AF64A, in rat. However, the optimal dose and the timeframe of administration of C3 are still unknown. In our studies, we revealed the concentration-dependent and time-dependent effects of C3 on AF64A-induced cholinergic lesion in rat. C3 was administered orally in 5, 10, and 25 mg/kg/day concentration, 7 days before and/or 7 days after intracerebroventricular (i.c.v.) AF64A administration. Our results have shown that 25 mg/kg/day C3 effectively protects against AF64A-generated cholinotoxicity if administered both 7 days before and 7 days after the AF64A injection. In contrast to these findings, administration of 5 or 10 mg/kg/day C3 or 25 mg/kg/day C3, given 7 days before or 7 days after stereotaxic AF64A injection, did not show cholinoprotective effects. In conclusion, the time-dependent effects of C3 on AF64A-induced cholinergic lesion suggest that C3 may act via the processes of both neuroprotection and neurorepair. Moreover, the effects of C3 depend largely on the administered dose of this low-molecular-weight GAG. The present findings also indicate that C3, administered in the effective concentration and timeframe, may play a pivotal role in the treatment of AD.
Alzheimer’s disease (AD) literature indicates that glycosaminoglycans (GAGs) may prevent proteoglycan-induced amyloid-β (Aβ) aggregation, decrease Aβ-induced tau-2 immunoreactivity, and increase the ...axonal growth and arborization of hippocampal neurons. However, there is no information about the impact of GAGs on cholinergic lesions. Here, AF64A was administered stereotaxically into the lateral ventricles of rats, at doses that are selective for cholinotoxicity (1 and 2
nmol). The heparin-derived oligosaccharide (HDO), C3 (25
mg/kg), was administered orally, once daily for 7 days before, and 7 days after AF64A administration. Choline acetyltransferase (ChAT) immunohistochemistry revealed that C3 administration reduced AF64A-induced cholinergic damage in the septum and cingulum bundle. Quantitative neuronal cell counts showed that C3 attenuated, by 60%, the decrease in cell number in the medial septum. Enzyme analysis showed that C3 also significantly restored ChAT (30%) and acetylcholinesterase (AChE) enzyme activity (45%), which had been diminished by AF64A. Our data suggest that, in addition to its effects of anti-Aβ aggregation, anti-Aβ-induced tau-2 immunoreactivity, and neurotrophic effects, C3 also effectively reduces AF64A-induced cholinergic damage; hence it may have potential therapeutic value in AD patients.
Abstract We aimed to determine the psychosocial and obstetric correlates of depressive symptomatology during pregnancy in South-Eastern Hungary. A total of 1719 women were screened for depression in ...four counties in 2006 and 2007, based on a Leverton Questionnaire (LQ) score of ≥12 at 14–24 weeks of gestation. The LQ scores indicated a probable depressive illness (PDI) in 17.2% of the study group. The best predictors in a multiple regression analysis were history of major depression (adjusted odds ratio AOR=3.23), and major life events (AOR=2.43). A perceived lack of social support from partner (AOR=1.79) and lack of support by family (AOR=1.23) were also significant determinants. Lack of planning of pregnancy (AOR=1.12) and a history of unfavourable obstetric outcome (AOR=1.42) also seem to predispose to PDI. Overall, psychosocial factors appeared important in the prediction of PDI, whereas economic features did not.
The authors describe the profile of performance of patients whose cognitive complaint is due to dementia, affective disorder, or combinations thereof on the Addenbrooke's Cognitive Examination (ACE) ...test battery.
Authors tested 90 subjects with dementia (63 Alzheimer disease AD; 27 fronto-temporal dementia FTD), 60 subjects with “pure” affective disorder (23 major depression MDD, 37 whose affective symptoms did not meet criteria for major depression Affective); 22 patients with symptoms of affective disorder and organic dementia (Mixed); and 127 healthy volunteers (NC).
The total ACE scores for the AD, FTD, and Mixed groups were significantly lower than for the NC group. Likewise, on total score, the AD and FTD groups scored significantly lower than either of the “pure” affective-disorder groups. Within the dementia group, the AD group scored significantly lower than the fronto-temporal group.
The profile of performance on the ACE of patients with dementia is different from that of patients suffering from affective illness. Mild impairment in the total ACE score, along with a low score on the memory domain tasks and letter fluency (in contrast to normal category fluency), are strongly indicative of an affective, as opposed to organic, pathology. A total score of <88 in suspected dementia patients with affective symptoms appears strongly predictive of an underlying organic disorder.
Ethylcholine aziridinium (AF64A) induces cholinergic lesion in animal models of AD. Although higher concentrations of AF64A are known to induce nonspecific, cholinergic, and non-cholinergic lesions, ...low concentrations are believed to be selectively cholinotoxic. However, morphological evidence of this phenomenon has not been demonstrated yet. The present study demonstrates that while AF64A damaged septal cholinergic fibers, periventricular GnRH-immunoreactive fibers remained intact, confirming the highly selective cholinotoxicity of AF64A at appropriate concentrations.
Diagnostic tools for dementia Hatfield, Catherine F; Dudas, Robert B; Dening, Tom
Maturitas,
07/2009, Letnik:
63, Številka:
3
Journal Article
Recenzirano
Abstract As population ageing means that dementia is becoming more prevalent, it is increasingly important that clinicians from all types of practice are familiar with assessing patients who have ...possible cognitive impairment. The diagnosis of the syndrome of dementia remains a clinical process, supplemented by relevant investigations including cognitive testing. This paper reviews some of the more commonly used tools for assessing cognition, behaviour and overall functioning in patients with possible or established dementia. Several categories of instruments are considered, including brief screening tests, neuropsychological test batteries, scales for behavioural and psychiatric symptoms, and functional and global assessments. It is recommended that clinicians familiarise themselves with a small number of scales that can be readily employed in everyday practice.
In the frame of a European Space Agency (ESA) project called ‘Biology and Physics in Space’, a returning satellite, Foton-M2, was orbiting a container, the BIOPAN-5, loaded with biological ...experiments and facilities for radiation dosimetry (RADO) in the open space. One of the RADO experiments was dedicated to the detection of the primary cosmic rays and secondary neutrons by a track etch detector stack. The system was calibrated at high-energy particle accelerators and neutron generators. The developed detectors were investigated by an image analyser, and from the track parameters the linear energy transfer spectra and the absorbed dose were determined (26 µGy/d). Also, the neutron flux was estimated below 5 MeV and found to be 2.4 cm−2 s−1 directly from the space. The construction of the stack allowed to investigate the neutrons also from the direction of the carrying satellite, where the flux was found somewhat higher.
The complex radiation field inside the International Space Station (ISS) as well as the dose received by its crew was studied for several years in the BRADOS
(
1
-
5
)
projects organized by the ...Institute for Biomedical Problems (IBMP, Moscow) with the participation of different laboratories. The results of the measurements performed during the BRADOS-5 project by a 3 axes solid state nuclear track detector (SSNTD) stack as LET spectra and dose values are presented. According to the results, no remarkable directional dependence could be observed in the radiation field. The averaged absorbed dose rate and dose equivalent rate values above
∼
12
keV
μ
m
-
1
were
27.0
±
1.6
μ
Gy
d
-
1
and
211.4
±
14.4
μ
Sv
d
-
1
, respectively, resulting in an averaged quality factor of
7.9
±
0.1
.
Purpose
To determine contributing psychosocial factors to postnatal depression (PND) in Hungary in 1996 and in 2006.
Methods
In 1996 and 2006, a total of 2,333 and 1,619 women, respectively, were ...screened for PND in South-Eastern Hungary, based on a Leverton questionnaire (LQ) score of ≥12 at 6–10 weeks after delivery.
Results
The LQ scores indicated an increase in PND from 15.0% in 1996 to 17.4% in 2006. The best predictors for PND in a multiple regression analysis were living in an urban environment adjusted odds ratio (AOR) = 11.26, unstable relationship (AOR = 3.1) and a perceived lack of social support from partner (AOR = 3.65) in 1996, and recent major life events (AOR = 3.38), unstable relationship (AOR = 3.84), self-reported low income (AOR = 1.82), and intention to return to work soon after delivery (AOR = 0.47) in 2006.
Conclusions
A self-defined low socioeconomic status and an intention to return to work have become significant factors in the development of PND. Besides the family factors recognized as salient variables in 1996, economic features came into prominence as newly identified main predictive factors for PND in 2006.
