Pathogenetic mechanisms in vascular dementia

Vascular dementia accounts for approximately 20% of all cases of dementia and for about 50% in subjects over 80 years. Thromboembolism with multiple cerebral infarcts was considered to be almost the only pathogenetic pathway of vascular dementia, with multi-infarct dementia as its clinical manifestation. However, there is a great heterogeneity of vascular dementia syndromes and pathological subtypes, as documented by the number of pathogenetic mechanisms now known to underlie the clinical picture. They include thromboembolism and extracerebral and cerebral factors. Among the extracerebral factors are ischemic hypoxic dementia (i.e., dementia due to hypoperfusion), vasculitis, hyperviscosity and abnormalities of hemostasis. Among the cerebral factors are lipohyalinosis, cerebral amyloid angiopathy, disruption of the blood-brain barrier and altered regulation of cerebral blood flow. Therefore, the approach to vascular dementia should take the heterogeneity into account. In this context, the importance of non-infarct type should be considered; subcortical white matter disorder seems to be a noteworthy common pathway of vascular dementia produced by various vascular mechanisms. Finally, the heterogeneity of the vascular mechanisms involved in vascular dementia-namely hypoperfusion-might be a factor that can be positively influenced by targeted therapeutic intervention

Усовершенствованный метод получения гептилового эфира 4-трифторацетилбензойной кислоты

A convenient three-step method for synthesis of heptyl (4-trifluoroacetyl)benzoate, an important neutral anion carrier, has been developed. The key step of the method is acylation of toluene by trifluoroacetic anhydride in presence of aluminium chloride at –8 – –10 oC. The procedure gives high overall yield and, unlike the earlier methods, does not include any organometallic reagents, therefore allowing scaling it up to several hundred grams, that makes the target compound much more readily available.Усовершенствованный метод получения гептилового эфира 4-трифторацетилбензойной кислоты Разработан удобный трeхстадийный метод синтеза гептилового эфира 4-трифторацетилбензойной кислоты, широко применяющегося в потенциометрическом анализе в качестве нейтрального переносчика анионов. Ключевой стадией метода является ацилирование толуола трифторуксусным ангидридом в присутствии хлорида алюминия при –8 – –10 oC. Данная процедура позволяет получить высокий общий выход продукта и, в отличие от описанных в литературе методик, не требует использования металлоорганических реагентов, что позволяет увеличить масштаб синтеза до сотен граммов и сделать целевой продукт значительно более доступным

Mitochondria-targeted antioxidant SkQ1 reverses glaucomatous lesions in rabbits

Original article is published in: Frontiers in Bioscience, Landmark, 20, 892–901, January 1, 2015Glaucoma is the main cause of irreversible blindness worldwide. This disease is characterized by apoptosis of retinal ganglion cells (RGC) and visual field loss that seems to be related to elevated intraocular pressure (IOP). Several lines of evidences have implicated the crucial role of mitochondrial dysfunction in the pathogenesis of glaucoma. Increased mitochondrial oxidative stress in RGC may underlie or contribute to susceptibility of RGC to apoptosis. In our work we (i) designed a rabbit model of chronic, moderately elevated IOP for studying glaucoma and (ii) demonstrated efficacy of mitochondria-targeted antioxidant SkQ1 as a tool to reverse several traits of experimental glaucoma induced by a series of injections of hydroxypropylmethylcellulose (HPMC) to the anterior chamber of the rabbit eye. It is shown that 6 months instillations of drops of 0.2.5–5 µM solution of SkQ1 normalize IOP and eye hydrodynamics and abolish an increase in lens thickness that accompanies glaucoma.Original article is published in: Frontiers in Bioscience, Landmark, 20, 892–901, January 1, 2015Glaucoma is the main cause of irreversible blindness worldwide. This disease is characterized by apoptosis of retinal ganglion cells (RGC) and visual field loss that seems to be related to elevated intraocular pressure (IOP). Several lines of evidences have implicated the crucial role of mitochondrial dysfunction in the pathogenesis of glaucoma. Increased mitochondrial oxidative stress in RGC may underlie or contribute to susceptibility of RGC to apoptosis. In our work we (i) designed a rabbit model of chronic, moderately elevated IOP for studying glaucoma and (ii) demonstrated efficacy of mitochondria-targeted antioxidant SkQ1 as a tool to reverse several traits of experimental glaucoma induced by a series of injections of hydroxypropylmethylcellulose (HPMC) to the anterior chamber of the rabbit eye. It is shown that 6 months instillations of drops of 0.2.5–5 µM solution of SkQ1 normalize IOP and eye hydrodynamics and abolish an increase in lens thickness that accompanies glaucoma

Phase diagram of superfluid 3He in "nematically ordered" aerogel

Results of experiments with liquid 3He immersed in a new type of aerogel are described. This aerogel consists of Al2O3 strands which are nearly parallel to each other, so we call it as a "nematically ordered" aerogel. At all used pressures a superfluid transition was observed and a superfluid phase diagram was measured. Possible structures of the observed superfluid phases are discussed.Comment: 6 pages, 8 figures. Submitted to Pis'ma v ZhETF (JETP Letters

Orbital glass and spin glass states of 3He-A in aerogel

Glass states of superfluid A-like phase of 3He in aerogel induced by random orientations of aerogel strands are investigated theoretically and experimentally. In anisotropic aerogel with stretching deformation two glass phases are observed. Both phases represent the anisotropic glass of the orbital ferromagnetic vector l -- the orbital glass (OG). The phases differ by the spin structure: the spin nematic vector d can be either in the ordered spin nematic (SN) state or in the disordered spin-glass (SG) state. The first phase (OG-SN) is formed under conventional cooling from normal 3He. The second phase (OG-SG) is metastable, being obtained by cooling through the superfluid transition temperature, when large enough resonant continuous radio-frequency excitation are applied. NMR signature of different phases allows us to measure the parameter of the global anisotropy of the orbital glass induced by deformation.Comment: 7 pages, 6 figures, Submitted to Pis'ma v ZhETF (JETP Letters

Long-way-to-go from bowel urinary diversion to neobladder

The history of the development of urinary diversion methods dates over than 170 years. During this time, many methods of urinary diversion have been invented. Some never made it out of the research centres, while others were widely accepted by urologists and still in use today. In modern bladder cancer, doctors are not only concerned about saving human life in the immediate period, but also about how the patient will live after the cystectomy, which is a crippling surgery that affects both the quality of life and the patients’ social adaptation. The article presents the historical stages of urinary diversion techniques from the first attempts at derivation into the undisturbed colon to the creation of a low-pressure high-capacity neobladders

Vascular Dementia Italian Sulodexide Study (VA.D.I.S.S.) Clinical and biological results

In order to evaluate the biological effects on some haemostasis factors of antithrombotic-hemorheological treatments on patients with vascular dementia, a multicenter, randomized, double-blind, double-dummy, study comparing sulodexide (Sdx, 50 mg bid orally for 6 months) and pentoxifylline (Ptx, 400 mg tid orally for six months) was carried out. Eighty-six patients, 46 in Sdx group, 40 in Ptx group, fulfilling the NINDS-AIREN criteria for probable vascular dementia were evaluated. Plasma fibrinogen levels showed a significant reduction in both groups, in patients with high basal levels ( 64350 mg/dl), the reduction being earlier in Sdx group (2nd month of therapy) than in Ptx group (4th month of therapy). In Sdx group a significant reduction in factor VII-Ag (baseline 102.8 U/dl; 6th month 90.1 U/dl) was also observed. Both drags induced a slight reduction in activated factor VII levels as well. A parallel improvement of G.B.S. Rating Scale for dementia scores was observed in Sdx group. These results seem to indicate that sulodexide treatment can have positive effects in vascular dementia

Vascular Dementia Italian Sulodexide Study (VA.D.I.S.S.) Clinical and biological results

In order to evaluate the biological effects on some haemostasis factors of antithrombotic-hemorheological treatments on patients with vascular dementia, a multicenter, randomized, double-blind, double-dummy, study comparing sulodexide (Sdx, 50 mg bid orally for 6 months) and pentoxifylline (Ptx, 400 mg tid orally for six months) was carried out. Eighty-six patients, 46 in Sdx group, 40 in Ptx group, fulfilling the NINDS-AIREN criteria for probable vascular dementia were evaluated. Plasma fibrinogen levels showed a significant reduction in both groups, in patients with high basal levels (≤350 mg/dl), the reduction being earlier in Sdx group (2nd month of therapy) than in Ptx group (4th month of therapy). In Sdx group a significant reduction in factor VII-Ag (baseline 102.8 U/dl; 6th month 90.1 U/dl) was also observed. Both drags induced a slight reduction in activated factor VII levels as well. A parallel improvement of G.B.S. Rating Scale for dementia scores was observed in Sdx group. These results seem to indicate that sulodexide treatment can have positive effects in vascular dementia

DSCo-NG: A Practical Language Modeling Approach for Time Series Classification

The abundance of time series data in various domains and their high dimensionality characteristic are challenging for harvesting useful information from them. To tackle storage and processing challenges, compression-based techniques have been proposed. Our previous work, Domain Series Corpus (DSCo), compresses time series into symbolic strings and takes advantage of language modeling techniques to extract from the training set knowledge about different classes. However, this approach was flawed in practice due to its excessive memory usage and the need for a priori knowledge about the dataset. In this paper we propose DSCo-NG, which reduces DSCo’s complexity and offers an efficient (linear time complexity and low memory footprint), accurate (performance comparable to approaches working on uncompressed data) and generic (so that it can be applied to various domains) approach for time series classification. Our confidence is backed with extensive experimental evaluation against publicly accessible datasets, which also offers insights on when DSCo-NG can be a better choice than others