The Method of Light Dose Measurement During Phodinamic Therapy

A new method of light dose monitoring during the photodynamic therapy of abdominal cavity organs was developed. To apply this method specially developed sensors were constructed. For these sensors the temporal and distance dependences of light doses were received and analyzed. It was shown that the light dose from the operating lamp is large enough in laser light field to be taken into account when planning photodynamic therapy. Keywords: PDT, light doses, other source of light in PDT, photodynamic therap

Endogenous Isoquinoline Alkaloids Agonists of Acid-Sensing Ion Channel Type 3

Acid-sensing ion channels (ASICs) ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development. In response to acidic stimuli, they can generate a unique biphasic current. At physiological pH 7.4, human ASIC3 isoform (hASIC3) is desensitized and able to generate only a sustained current. We found endogenous isoquinoline alkaloids (EIAs), which restore hASIC3 from desensitization and recover the transient component of the current. Similarly, rat ASIC3 isoform (rASIC3) can also be restored from desensitization (at pH < 7.0) by EIAs with the same potency. At physiological pH and above, EIAs at high concentrations were able to effectively activate hASIC3 and rASIC3. Thus, we found first endogenous agonists of ASIC3 channels that could both activate and prevent or reverse desensitization of the channel. The decrease of EIA levels could be suggested as a novel therapeutic strategy for treatment of pain and inflammation

Кластерный анализ результатов интраоперационной оптической спектроскопической диагностики в нейрохирургии глиальных опухолей головного мозга

The paper presents the results of a comparative study of methods of cluster analysis of optical intraoperative spectroscopy data during surgery of glial tumors with varying degree of malignancy. The analysis was carried out both for individual patients and for the entire dataset. The data were obtained using combined optical spectroscopy technique, which allowed simultaneous registration of diffuse reflectance spectra of broadband radiation in the 500–600 nm spectral range (for the analysis of tissue blood supply and the degree of hemoglobin oxygenation), fluorescence spectra of 5‑ALA induced protoporphyrin IX (Pp IX) (for analysis of the malignancy degree) and signal of diffusely reflected laser light used to excite Pp IX fluorescence (to take into account the scattering properties of tissues). To determine the threshold values of these parameters for the tumor, the infltration zone and the normal white matter, we searched for the natural clusters in the available intraoperative optical spectroscopy data and compared them with the results of the pathomorphology. It was shown that, among the considered clustering methods, EM‑algorithm and k‑means methods are optimal for the considered data set and can be used to build a decision support system (DSS) for spectroscopic intraoperative navigation in neurosurgery. Results of clustering relevant to thepathological studies were also obtained using the methods of spectral and agglomerative clustering. These methods can be used to postprocess combined spectroscopy data.В работе представлены результаты сравнительного исследования методов кластерного анализа данных оптической интраоперационной спектроскопии при проведении операций по удалению глиальных опухолей различной степени злокачественности. Анализ проведен как для отдельных пациентов, так и для всей совокупности данных. Данные были получены методом комбинированной оптической спектроскопии, регистрирующим спектр диффузного отражения широкополосного излучения в диапазоне спектра 500–600 нм (с целью анализа кровенаполненности тканей и степени оксигенации гемоглобина), спектр флуоресценции индуцированного 5‑аминолевулиновой кислотой протопорфирина IX (с целью анализа степени изменения тканей) и сигнал диффузно отраженного лазерного излучения, использовавшегося для возбуждения флуоресценции (с целью учета рассеивающих свойств тканей). Для определения пороговых значений указанных параметров для опухоли, зоны инфильтрации и нормального белого вещества был проведен поиск естественных кластеров в имеющихся интраоперационных данных оптической спектроскопии и их сопоставление с результатами патоморфологической экспертизы. Было показано, что среди рассмотренных методов кластеризации ЕМ‑алгоритм и метод k‑средних оптимальны для рассмотренного набора данных и могут быть использованы для построения системы поддержки принятия решений при спектроскопической интраоперационной навигации в нейрохирургии. Релевантные результатам патоморфологических исследований модели были также получены с помощью методов спектральной и агломеративной кластеризации. Эти методы могут быть использованы для постобработки данных комбинированной спектроскопии

Cluster analysis of the results of intraoperative optical spectroscopic diagnostics In brain glioma neurosurgery

The paper presents the results of a comparative study of methods of cluster analysis of optical intraoperative spectroscopy data during surgery of glial tumors with varying degree of malignancy. The analysis was carried out both for individual patients and for the entire dataset. The data were obtained using combined optical spectroscopy technique, which allowed simultaneous registration of diffuse reflectance spectra of broadband radiation in the 500–600 nm spectral range (for the analysis of tissue blood supply and the degree of hemoglobin oxygenation), fluorescence spectra of 5‑ALA induced protoporphyrin IX (Pp IX) (for analysis of the malignancy degree) and signal of diffusely reflected laser light used to excite Pp IX fluorescence (to take into account the scattering properties of tissues). To determine the threshold values of these parameters for the tumor, the infltration zone and the normal white matter, we searched for the natural clusters in the available intraoperative optical spectroscopy data and compared them with the results of the pathomorphology. It was shown that, among the considered clustering methods, EM‑algorithm and k‑means methods are optimal for the considered data set and can be used to build a decision support system (DSS) for spectroscopic intraoperative navigation in neurosurgery. Results of clustering relevant to thepathological studies were also obtained using the methods of spectral and agglomerative clustering. These methods can be used to postprocess combined spectroscopy data

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

Plant lignans exhibit a wide range of biological activities, which makes them the research objects of potential use as therapeutic agents. They provide diverse naturally-occurring pharmacophores and are available for production by chemical synthesis. A large amount of accumulated data indicates that lignans of different structural groups are apt to demonstrate both anti-inflammatory and antioxidant effects, in many cases, simultaneously. In this review, we summarize the comprehensive knowledge about lignan use as a bioactive agent in disorders associated with oxidative stress and inflammation, pharmacological effects in vitro and in vivo, molecular mechanisms underlying these effects, and chemical synthesis approaches. This article provides an up-to-date overview of the current data in this area, available in PubMed, Scopus, and Web of Science databases, screened from 2000 to 2022

Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3)

Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs—peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain

Retinoic Acid-Differentiated Neuroblastoma SH-SY5Y Is an Accessible In Vitro Model to Study Native Human Acid-Sensing Ion Channels 1a (ASIC1a)

Human neuroblastoma SH-SY5Y is a prominent neurobiological tool used for studying neuropathophysiological processes. We investigated acid-sensing (ASIC) and transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) ion channels present in untreated and differentiated neuroblastoma SH-SY5Y to propose a new means for their study in neuronal-like cells. Using a quantitative real-time PCR and a whole-cell patch-clamp technique, ion channel expression profiles, functionality, and the pharmacological actions of their ligands were characterized. A low-level expression of ASIC1a and ASIC2 was detected in untreated cells. The treatment with 10 μM of retinoic acid (RA) for 6 days resulted in neuronal differentiation that was accompanied by a remarkable increase in ASIC1a expression, while ASIC2 expression remained almost unaltered. In response to acid stimuli, differentiated cells showed prominent ASIC-like currents. Detailed kinetic and pharmacological characterization suggests that homomeric ASIC1a is a dominant isoform among the present ASIC channels. RA-treatment also reduced the expression of TRPV1 and TRPA1, and minor electrophysiological responses to their agonists were found in untreated cells. Neuroblastoma SH-SY5Y treated with RA can serve as a model system to study the effects of different ligands on native human ASIC1a in neuronal-like cells. This approach can improve the characterization of modulators for the development of new neuroprotective and analgesic drugs