Intracellular Cholesterol Lowering as Novel Target for Anti‐Atherosclerotic Therapy

Atherosclerosis and disorders associated with cardiovascular system remain the major problem of modern medicine and the leading cause of mortality in developed countries. According to the current knowledge, atherosclerosis development can begin early in life. Clinically silent early‐stage lesions can be detected in a large population of young adults. Despite substantial progress in the recent years, therapy of atherosclerosis mostly remains limited to plasma lipid profile correction. Moreover, no therapy is currently available for the treatment of asymptomatic early stages of the disease. The existing synthetic drugs could not be used for this purpose, because of the unfavourable risk/benefit ratio and high cost of treatment, which has to be long‐lasting. In this regard, medications based on natural agents with anti‐atherosclerotic activity may offer interesting possibilities. Current research should focus on detection and evaluation of such agents. One of the important tools for anti‐atherosclerotic drug evaluation is a cell‐based model, which allows measurement of intracellular lipid accumulation. Anti‐atherosclerotic activity of various substances can therefore be evaluated by the decrease of intracellular lipid storage. In this chapter, we will discuss the development and application of cellular models based on primary culture of human arterial wall cells that are suitable for detection and measurement of anti‐atherosclerotic activity of various substances. Using these models, several natural agents have been successfully evaluated, which led to the development of pharmaceutical products with anti‐atherosclerotic activity based on botanicals

Regression in the Symptoms and Discal Hernia in Case of Lumbar Radiculopathy

BACKGROUND: Discogenic lumbar radiculopathy has a favorable potential for survival; the regression of clinical symptoms may outpace the subsidence of discal hernia. AIM: The objective of the study is comparing the clinical data and the results of magnetic resonance imaging (MRI) in patients with discogenic lumbar radiculopathy over 1 year of observation. MATERIALS AND METHODS: Thirty-two patients (13 males at the average age of 39.1 ± 11.8 years) with discogenic lumbar radiculopathy confirmed by MRI were examined in the study. The intensity of pain condition was assessed using the numerical rating scale; disability was assessed using the Oswestry disability index. Sixteen patients were subjected to repeated MRI. RESULTS: Statistically significant (p < 0.01) reduction of the average pain intensity and intensity of disability more than 2 times was observed as early as in the first 2 weeks. Gradual reduction of pain and disability was observed during the year. Reduction of discal hernia by more than 50% was observed on average after 8.7 ± 4.7 months. CONCLUSION: In the case of discogenic radiculopathy, the reduction of pain and related disability far outstrips the regression of the herniation of intervertebral disk

Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases

Low-density lipoprotein (LDL) plays a key role in the development and progression of atherosclerosis and cardiovascular disease. LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and intermediate and small dense (sd) LDLs. It has been well documented that sdLDL has a greater atherogenic potential than that of other LDL subfractions and that sdLDL cholesterol (sdLDL-C) proportion is a better marker for prediction of cardiovascular disease than that of total LDL-C. Circulating sdLDL readily undergoes multiple atherogenic modifications in blood plasma, such as desialylation, glycation, and oxidation, that further increase its atherogenicity. Modified sdLDL is a potent inductor of inflammatory processes associated with cardiovascular disease. Several laboratory methods have been developed for separation of LDL subclasses, and the results obtained by different methods can not be directly compared in most cases. Recently, the development of homogeneous assays facilitated the LDL subfraction analysis making possible large clinical studies evaluating the significance of sdLDL in the development of cardiovascular disease. Further studies are needed to establish guidelines for sdLDL evaluation and correction in clinical practice

Association of PIP4K2A Polymorphisms with Alcohol Use Disorder

Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. Methods: 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CIIIA). Results: Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. Conclusions: For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula

Clinical evaluation of different treatment strategies for motor recovery in poststroke rehabilitation during the first 90 days

Background: Motor recovery after stroke is based on neuronal plasticity and the structural reorganization of the brain. Questions are debated about the proper moment to start rehabilitation in the acute period of stroke, the significance of rehabilitation interventions during the so-called “plastic window”, and the advantages of modern and traditional programs. The aims of this study were to evaluate the role of different rehabilitation strategies and their combinations for motor recovery and the impact on functional disability by way of neurological and functional outcomes 3 months after ischemic stroke. Methods: We used three rehabilitation approaches: early rehabilitation from the first day of stroke (Phase I), traditional exercise programs (Phase II), and an author’s new method of biofeedback rehabilitation using motion sensors and augmented reality (AR) rehabilitation (Phase III). Clinical and functional outcomes were measured on the 90th day after stroke. We developed algorithms for quantifying the quality of movements during the execution of tasks in the motor domains of the AR rehabilitation program. Results: Phase I of rehabilitation led to an improvement in functional independence, and the recovery of motor functions of the extremities with an absence of mortality and clinical deterioration. AR rehabilitation led to significant improvement both with respect to clinical and functional scores on scales and to variables reflecting the quality of movements. Patients who were actively treated during Phases II and III achieved the same final level of motor recovery and functional outcomes as that of participants who had only received AR rehabilitation during Phase III. Patients who underwent outpatient observation after Phase I showed a deficit of spontaneous motor recovery on the 90th day after stroke. Conclusions: Early rehabilitation was successful but was not enough; rehabilitation programs should be carried out throughout the entire “sensitive period” of poststroke plasticity. The newly developed AR biofeedback motion training is effective and safe as a separate rehabilitation method in the early recovery period of moderately severe, hemiparalytic, and ischemic stroke. These two rehabilitation approaches must be applied together or after each other, not instead of each other, as shown in clinical practice

Serum BDNF's Role as a Biomarker for Motor Training in the Context of AR-Based Rehabilitation after Ischemic Stroke

BACKGROUND: brain-derived neurotrophic factor (BDNF) may play a role during neurorehabilitation following ischemic stroke. This study aimed to elucidate the possible role of BDNF during early recovery from ischemic stroke assisted by motor training. METHODS: fifty patients were included after acute recovery from ischemic stroke: 21 first received classical rehabilitation followed by 'motor rehabilitation using motion sensors and augmented reality' (AR-rehabilitation), 14 only received AR-rehabilitation, and 15 were only observed. Serum BDNF levels were measured on the first day of stroke, on the 14th day, before AR-based rehabilitation (median, 45th day), and after the AR-based rehabilitation (median, 82nd day). Motor impairment was quantified clinically using the Fugl-Meyer scale (FMA); functional disability and activities of daily living (ADL) were measured using the Modified Rankin Scale (mRS). For comparison, serum BDNF was measured in 50 healthy individuals. RESULTS: BDNF levels were found to significantly increase during the phase with AR-based rehabilitation. The pattern of the sequentially measured BDNF levels was similar in the treated patients. Untreated patients had significantly lower BDNF levels at the endpoint. CONCLUSIONS: the fluctuations of BDNF levels are not consistently related to motor improvement but seem to react to active treatment. Without active rehabilitation treatment, BDNF tends to decrease

The formation of eyeball musculoskeletal stump using a Ni-Ti implant in vivo

The purpose of this study is to investigate the possibility of forming an eyeball musculoskeletal stump using a Ni-Ti implant in vivo. Studies were performed on 18 Wistar rats. The animals were enucleated one of eyes. After the enucleation the musculoskeletal stump using Ni-Ti implant was formed. Ni-Ti implant was made from a thread of porous Ni-Ti (TN-10) with a thickness of 100 [mu]m. Before implantation the Ni-Ti implant was sterilized by ethylene oxide. Results showed that the Ni-Ti implant surface was uniform and had not visible defects. The NiTi implant surface was a hydrophobic with the mean value of [theta]=93.5°±1.4. The Ni-Ti implant in the eye orbit was mobile. The Ni-Ti implantation into the eye orbit contributed the connective tissue with blood vessels formation and insignificant leucocytes infiltration (macrophages and lymphocytes infiltration). The study showed the possibility of forming an eyeball musculoskeletal stump using a Ni-Ti implant