Dimebon Does Not Ameliorate Pathological Changes Caused by Expression of Truncated (1–120) Human Alpha-Synuclein in Dopaminergic Neurons of Transgenic Mice

Background: Recent clinical studies have demonstrated that dimebon, a drug originally designed and used as a non-selective antihistamine, ameliorates symptoms and delays progress of mild to moderate forms of Alzheimer’s and Huntington’s diseases. Although the mechanism of dimebon action on pathological processes in degenerating brain is elusive, results of studies carried out in cell cultures and animal models suggested that this drug might affect the process of pathological accumulation and aggregation of various proteins involved in the pathogenesis of proteinopathies. However, the effect of this drug on the pathology caused by overexpression and aggregation of alpha-synuclein, including Parkinson’s disease (PD), has not been assessed. Objective: To test if dimebon affected alpha-synuclein-induced pathology using a transgenic animal model. Methods: We studied the effects of chronic dimebon treatment on transgenic mice expressing the C-terminally truncated (1–120) form of human alpha-synuclein in dopaminergic neurons, a mouse model that recapitulates several biochemical, histopathological and behavioral characteristics of the early stage of PD. Results: Dimebon did not improve balance and coordination of aging transgenic animals or increase the level of striatal dopamine, nor did it prevent accumulation of alpha-synuclein in cell bodies of dopaminergic neurons. Conclusion: Our observations suggest that in the studied model of alpha-synucleinopathy dimebon has very limited effect on certain pathological alterations typical of PD and related diseases

Correlations and age-related changes in central and peripheral hemodynamic parameters

BACKGROUND: One of the current issues of fundamental and clinical medicine is the early diagnosis of pathological changes that may lead to the development of cardiovascular disease. AIM: The study aimed to investigate age-related changes in the cardiovascular system in healthy individuals by a comprehensive assessment of the correlations between hemodynamic and microcirculatory parameters at different age. METHODS: The study was conducted on 136 adult volunteers with no clinical or laboratory manifestations of cardiovascular disease. The material was divided into five age groups: adolescence, I and II periods of adulthood, old age, and senile age. Males and females accounted for 50.73% and 49.27%, respectively. Central and peripheral hemodynamic parameters were measured using high-resolution compression oscillometry, ultrasound duplex scanning of aortic arch branches, echocardiography, and reactive hyperemia test on the brachial artery. Microcirculation indices in the skin of the right index finger were studied using a laser Doppler flowmeter before and after the treadmill test. The digital data were processed by the methods of variation statistics using the JASP 0.16.4.0 statistical software package. RESULTS: An age-related decrease in skin microcirculation indices was observed. A significant statistical dependence of changes in microcirculation indices after physical activity in the groups of old and senile age was found. Left ventricular ejection fraction, cardiac output, cardiac index, stroke volume, and stroke index progressively decreased with increasing age; diastolic blood pressure increased; pliability of the brachial artery vascular wall decreased; total and specific peripheral resistance increased. Blood flow indices in the common carotid arteries (diameter and linear and volumetric blood flow velocity) decreased, whereas resistance index and intima-media thickness increased. Blood flow indices in vertebral arteries (linear and volumetric blood flow velocity) and indices of total blood flow to the brain progressively decreased with age. In addition, the dependence of some indices on gender was revealed. CONCLUSIONS: With increasing age in healthy people, changes in central and peripheral hemodynamic parameters occur, which do not lead to cardiovascular diseases. Age-related changes in macro- and microcirculation are best detected during functional stress tests and should be considered in clinical practice as a manifestation of the normal aging process

Development of oral cancer tissue-mimicking phantom based on polyvinyl chloride plastisol and graphite for terahertz frequencies

SIGNIFICANCE: A new concept of a biotissue phantom for terahertz (THz) biomedical applications is needed for reliable and long-term usage. AIM: We aimed to develop a new type of biotissue phantom without water content and with controllable THz optical properties by applying graphite powders into a polyvinyl chloride plastisol (PVCP) matrix and to give a numerical description to the THz optical properties of the phantoms using the Bruggeman model (BM) of the effective medium theory (EMT). APPROACH: The THz optical properties of graphite and the PVCP matrix were measured using THz time-domain spectroscopy, which works in the frequency range from 0.1 to 1 THz. Two phantoms with 10% and 12.5% graphite were fabricated to evaluate the feasibility of describing phantoms using the EMT. The EMT then was used to determine the concentration of graphite required to mimic the THz optical properties of human cancerous and healthy oral tissue. RESULTS: The phantom with 16.7% of graphite has the similar THz optical properties as human cancerous oral tissue in the frequency range of 0.2 to 0.7 THz. The THz optical properties of the phantom with 21.9% of graphite are close to those of human healthy oral tissue in the bandwidth from 0.6 to 0.8 THz. Both the refractive index and absorption coefficient of the samples increase with an increase of graphite concentration. The BM of the EMT was used as the numerical model to describe the THz optical properties of the phantoms. The relative error of the BM for the refractive index estimation and the absorption coefficient is up to 4% and 8%, respectively. CONCLUSIONS: A water-free biotissue phantom that mimics the THz optical properties of human cancerous oral tissue was developed. With 21.9% of graphite, the phantom also mimics human healthy oral tissue in a narrow frequency range. The BM proved to be a suitable numerical model of the phantom

Development of oral cancer tissue-mimicking phantom based on polyvinyl chloride plastisol and graphite for terahertz frequencies

Abstract Significance: A new concept of a biotissue phantom for terahertz (THz) biomedical applications is needed for reliable and long-term usage. Aim: We aimed to develop a new type of biotissue phantom without water content and with controllable THz optical properties by applying graphite powders into a polyvinyl chloride plastisol (PVCP) matrix and to give a numerical description to the THz optical properties of the phantoms using the Bruggeman model (BM) of the effective medium theory (EMT). Approach: The THz optical properties of graphite and the PVCP matrix were measured using THz time-domain spectroscopy, which works in the frequency range from 0.1 to 1 THz. Two phantoms with 10% and 12.5% graphite were fabricated to evaluate the feasibility of describing phantoms using the EMT. The EMT then was used to determine the concentration of graphite required to mimic the THz optical properties of human cancerous and healthy oral tissue. Results: The phantom with 16.7% of graphite has the similar THz optical properties as human cancerous oral tissue in the frequency range of 0.2 to 0.7 THz. The THz optical properties of the phantom with 21.9% of graphite are close to those of human healthy oral tissue in the bandwidth from 0.6 to 0.8 THz. Both the refractive index and absorption coefficient of the samples increase with an increase of graphite concentration. The BM of the EMT was used as the numerical model to describe the THz optical properties of the phantoms. The relative error of the BM for the refractive index estimation and the absorption coefficient is up to 4% and 8%, respectively. Conclusions: A water-free biotissue phantom that mimics the THz optical properties of human cancerous oral tissue was developed. With 21.9% of graphite, the phantom also mimics human healthy oral tissue in a narrow frequency range. The BM proved to be a suitable numerical model of the phantom