Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency.This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD. Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease.The potential for cannabis to enhance the quality of life of Parkinson’s patients is explored

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

Background: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE CS), it acts not as a proteinase, but as a receptor for a 1proteinase inhibitor (a 1PI, a 1antitrypsin, SerpinA1). Binding of a1PI to HLECS forms a motogenic complex. We previously demonstrated that a1PI deficiency attends HIV-1 disease and that a1PI augmentation produces increased numbers of immunocompetent circulating CD4 + lymphocytes. Herein we investigated the mechanism underlying the a 1PI deficiency that attends HIV-1 infection. Methods and Findings: Active a 1PI in HIV-1 subjects (median 17 mM, n = 35) was significantly below normal (median 36 mM, p,0.001, n = 30). In HIV-1 uninfected subjects, CD4 + lymphocytes were correlated with the combined factors a1PI, HLECS + lymphocytes, and CXCR4 + lymphocytes (r 2 = 0.91, p,0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with.220 CD4 cells/ml, CD4 + lymphocytes were correlated solely with active a 1PI (r 2 =0.93,p,0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human a 1PI. Chimpanzee a 1PI differs from human a1PI by a single amino acid within the 3F5-binding epitope. Unlike human a1PI, chimpanzee a1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4 + lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-a 1PI immune complexes correlated with decreased CD4 + lymphocytes in HIV-1 subjects

Role of compliance in Helicobacter pylori eradication treatment : Results of the European Registry on H. pylori management

Peer reviewe

МОДЕЛИРОВАНИЕ ИНТЕРНАЛИЗАЦИИ ВОДОРАСТВОРИМЫХ ПРОТИВООПУХОЛЕВЫХ ЦИТОСТАТИКОВ В ТОНКОЙ КИШКЕ ЭКСПРЕСС-МЕТОДОМ EX VIVO С ПОМОЩЬЮ ХЕМИЛЮМИНЕСЦЕНЦИИ

Introduction. the ability of the small intestine (internalization) to absorb water-soluble anticancer cytostatics determines the possibility of their oral administration. the ex-vivo express method that simulates the internalization of substances using a modified technique of an isolated «inverted» segment of the rat small intestine with flash chemiluminescence is adequate to solve the problem. Objectives: to evaluate the absorption of the new water-soluble anticancer cytostatics with different properties from the rat small intestine for preclinical study by oral administration. Material and methods. conjugated with acridinium (Acridinium NHS Ester, Toronto Research Chemicals, Canada) cytostatics were studied: low molecular weight (1) anthrafuran-acridinium (MW 0.8 kDa) and high molecular weight (2) aimpila-acridinium (MW 105 kDa) and (3) L-lysine-α-oxidase (LO-acridinium, MW 122 kDa). absorption was determined in a modified model of an isolated «inverted» segment of the rat small intestine using flash-chemiluminescence with the calculation of the relative light units (RLu). Results. It was shown that the absorption level of acridinium-conjugated cytostatics depending on molar concentration ranged from 55 % (1) to 1.7–11 % (2, 3) and 2500 (1) to 9.2–188 nmol/l (2, 3), respectively. the level of internalized anthrafuran-acridinium (55 %) was consistent with the known value of the effective non-conjugated cytostatic oral dose, which was two times higher than equitherapeutical parenteral dose: 100 mg/kg vs 50 mg/kg. Conclusion. the data obtained allow us to consider ex vivo express method for preclinical study of the various water-soluble anticancer cytostatics for screening and identification of an opportunity for oral administration and estimation of starting dose. the method has a good correlation with in vivo tests and economically favorable due to a quick response and small number of the tested agent.Введение. Способность к всасыванию в тонкой кишке (интернализация) водорастворимых противоопухолевых цитостатиков определяет возможность их перорального применения. Экспресс-метод ex vivo, моделирующий интернализацию веществ в рамках модифицированной методики изолированного «вывернутого» отрезка тонкой кишки крысы с импульсной хемилюминесценцией, адекватен для решения поставленной задачи. Цель исследования – оценка всасывания в организм из тонкой кишки новых водорастворимых противоопухолевых цитостатиков с различными свойствами для доклинического изучения при пероральном введении. Материал и методы. В исследование включены конъюгированные с Акридином (Acridinium NHS Ester, Toronto Research Chemicals, Canada) цитостатики: низкомолекулярный (1) Антрафуран-Акридин (MW 0,8 кДа) и высокомолекулярные (2) Аимпила-Акридин (MW 105 кДа) и (3) L-лизин-α-оксидаза (ЛО-Акридин, MW 122 кДа). Всасывание определено в модифицированной модели изолированного «вывернутого» отрезка тонкой кишки крысы методом импульсной флэш-хемилюминесценции и пересчитано в процентах. Результаты. Показано, что в зависимости от молярной концентрациии от 2500 (1) до 9,2–188 нмоль/л (2, 3) уровень всасывания конъюгированных с Акридином цитостатиков находится в диапазоне от 55 % (1) до 1,7–11 % (2, 3) соответственно. Уровень всасывания конъюгированного Антрафурана (55 %) согласуется с величиной известной эффективной пероральной дозы неконъюгированного цитостатика, которая была в два раза больше, чем эквитерапевтическая парентеральная доза: 100 мг/кг против 50 мг/кг. Заключение. Полученные данные позволяют рассматривать экспресс-метод ex vivo для скрининга возможности доклинического изучения различных водорастворимых противоопухолевых цитостатиков при пероральном введении с прогнозированием стартовой дозы. Метод адекватен тестам in vivo и экономически целесообразен в силу быстрого ответа и малого количества тестируемого агента

Gender differentiation and its connection to linguistics

According to Wilhelm von Humboldt, the founder of the philosophy of language, the formation of objects and concepts in our minds, as well as everything we receive from the outside, is achieved through language. Our understanding of the world is possible through the use of culture and language. That is, if there were no language, there would be no intelligence. Because of the culture and intelligence, we acquire through language, each person exists as a reflection of the prevailing worldview. Each stage of cultural development is connected and comprehended through language. Language is not a tool for describing the known, but a tool for discovering the unknown. The true power of language lies in its constructiveness

Cannabis Pharmacogenomics: A Path to Personalized Medicine

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and concerns regarding the cannabis/cannabinoid treatment and help us to understand the variability in individual responses and associated risks. Pharmacogenomics research has made meaningful progress in identifying genetic variations that play a critical role in interpatient variability in response to cannabis. This review classifies the current knowledge of pharmacogenomics associated with medical marijuana and related compounds and can assist in improving the outcomes of cannabinoid therapy and to minimize the adverse effects of cannabis use. Specific examples of pharmacogenomics informing pharmacotherapy as a path to personalized medicine are discussed

COVID-19 Pharmacotherapy: Drug Development, Repurposing of Drugs, and the Role of Pharmacogenomics

The SARS-CoV-2 virus has been the subject of intense pharmacological research. Various pharmacotherapeutic approaches including antiviral and immunotherapy are being explored. A pandemic, however, cannot depend on the development of new drugs; the time required for conventional drug discovery and development is far too lengthy. As such, repurposing drugs is being used as a viable approach for identifying pharmacological agents for COVID-19 infections. Evaluation of repurposed drug candidates with pharmacogenomic analysis is being used to identify near-term pharmacological remedies for COVID-19

Pharmacogenomics Informs Cardiovascular Pharmacotherapy

Precision medicine exemplifies the emergence of personalized treatment options which may benefit specific patient populations based upon their genetic makeup. Application of pharmacogenomics requires an understanding of how genetic variations impact pharmacokinetic and pharmacodynamic properties. This particular approach in pharmacotherapy is helpful because it can assist in and improve clinical decisions. Application of pharmacogenomics to cardiovascular pharmacotherapy provides for the ability of the medical provider to gain critical knowledge on a patient\u27s response to various treatment options and risk of side effects

Peculiarities of TP-e.m.f. caused by the heating of charge carriers by an electric field in a layered semiconductor n-InSe

The effect of the external and intracrystalline factors (temperature, light, and the magnitude of the initial dark resistivity of the sample, electric field, chemical nature, and amount of the impurities) on the main characteristics of layered n-InSe crystals was investigated. The thermophoto-e.m.f. (TP-e.m.f.) was observed due to the heating of free charge carriers by an electric field. It has been established that the obtained experimental results differ significantly from spatially homogeneous semiconductors. This deviation increases with an increase in the value of the initial dark resistivity of the sample (ρD0) which depends nonmonotonically on the concentration of the impurity (NREE). Undoped (with the lowest ρD0) and rare-earth-doped (NREE ≥ 5·10–2 at.%) samples were studied under all conditions, as well as at high T0 and I0, and it was determined that the TP-e.m.f. characteristics of hot current carriers (HCC) are the most stable and reproducible. The obtained results satisfactorily correlate with the provisions of the theory of TP-e.m.f. of HCC in spatially homogeneous semiconductors. The dependence of the characteristics of TP-e.m.f. of HCC from ρD0 and NREE clearly explains the deviations compared to spatially homogeneous semiconductors considering the presence of random macroscopic defects in the samples

Immunologic aspects of pathogenesis of endometrial disease

Endometrioid disease (ED) is multifactorial nature of etiopathogenesis. Since the control of hemostasis in human tissue provided by the immune system, it is clear that the basis of violations of the timely elimination of the altered cells are the body's immunological disorders. Consequently, the basis of endometriosis should lie immune disorders. The article is devoted to the currently existing problems and controversial issues in relation to the pathogenesis of external genital endometriosis. The review presents the national and international research, as well as its own approach to the problem, the prospects and possible solutions