Assessment of the photosensitizer efficacy after determination of threshold doses initiating erythrocyte hemolysis

Purpose: To find out a technique for determining the effectiveness of porphyrin-type photosensitizers with concentrations which cause hemolysis in erythrocytes (hemolysis threshold). The hemolysis threshold is found under the following conditions: irradiation in the Soret band with standard parameters – power density, exposure dose, irradiation time.Material and methods. Phototherapeutic device “AST” (LLC “Pankov-medical”) – average power 0.5 W, wavelength ≈ 405 nm. Rat blood erythrocytes. “Multiscan MS” device manufactured by Labsystems, Finland. Preparation “Dimegin”, hematoporphyrin derivative; preparation “Photoditazine” (LLC “VETA-GRAND”), chlorine E6 derivative.Results. On analyzing the results obtained after experimentation with the abovementioned two preparations, it was shown that the developed technique has a high efficacy. It was also shown that the studied photosensitizers are equally effective when irradiated in the Soret band.Conclusion. The developed technique is simple and easy to use. It helps to assess the efficacy of various photosensitizers thus, facilitating the selection of their necessary concentrations for managing different diseases.

Study of toxicity and peculiarities of biological effects of nanocomposite pectin-Ag: results of a subchronic experiment

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields. Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20-30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed. Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase. Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.

Performance Testing of Eye Lens Dosemeter and Evaluation of Personal Radiological Exposition at Douera Orthopedic Interventional Service

The radiological monitoring of the eye in the workplace depends on the type of dosemeter used and its performance. The dosimetric performances of Nuclear Research Center of Algiers (CRNA) developed eye lens dosemeter (Larabi-Harfouche et al. Characterization and qualification of a CRNA eye dosimeter. Perspect Sci. 12, 100402 (2019)) are investigated in this work in order to assess its ability to measure the operational quantity Hp(3) in photon fields and to check its compliance with the International Commission on Radiological Protection recommendations for professionally exposed people (ICRP. ICRP statement on tissue reactions/early and late effects of radiation in normal tissues and organs – threshold doses for tissue reactions in a radiation protection context. ICRP Publication 118. Ann. ICRP 41(1/2) (2012)). Some key performance indicators including the relative response of the nonlinearity, coefficient of variation, and photon energy and angular dependence are assessed before the use of this dosemeter for eye lens monitoring of orthopedic staff in the operating room at Douera hospital. The monitoring results of this first pilot study are presented and discussed in view of supporting the recommendations of the International Organization for Standardization 15382: 2015 concerning the monitoring of the dose at lens.

How to Measure/Calculate Radiation Dose in Patients?

Patients in fluoroscopically guided interventions (FGI) may be exposed to substantial radiation dose levels (SRDL). The most commonly reported adverse reactions are skin injuries with erythema or necrosis. It is therefore important for the interventional radiologist to know deterministic effects with their threshold doses. If possible all relevant modality parameters should be displayed on the interventionalists screen. Dosimetric parameters should be displayed in digital imaging and communications in medicine (DICOM) units and stored as DICOM Radiation Dose Structured Report (RDSR). The peak skin dose (PSD) is the most relevant risk parameter for skin injuries. Dose management systems (DMS) help optimising radiation exposure of patients. However, their calculation of skin dose maps is only available after a FGI. Therefore, dose maps and PSD should preferably be calculated and displayed in real time by the modality.

Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle

Background Currently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect. We have previously shown that three anoctamin 1 (ANO1) antagonists mediate potent relaxation of precontracted human uterine smooth muscle (USM). In this study, we aimed to determine whether a combination of sub-relaxatory doses of tocolytic drugs in current clinical use [the L-type voltage-gated calcium channel (VGCC) blocker, nifedipine (NIF); and the β2-adrenergic (β2AR) agonist, terbutaline (TRB)] will potentiate USM relaxation with two ANO1 antagonists [benzbromarone (BB) and MONNA (MN)]. Objective This study sought to examine the synergistic potency and mechanistic basis of two ANO1 antagonists with currently available tocolytic drugs. Functional endpoints assessed included relaxation of pre-contracting pregnant human USM tissue, inhibition of intracellular calcium release, and reduction of spontaneous transient inward current (STIC) recordings in human uterine smooth muscle cells. Methods Human myometrial strips and primary human USM cells were used in organ bath and calcium flux experiments with different combinations of sub-threshold doses of ANO1 antagonists and terbutaline or nifedipine to determine if ANO1 antagonists potentiate tocolytic drugs. Results The combination of sub-threshold doses of two ANO1 antagonists and current tocolytic drugs demonstrate a significant degree of synergy to relax human pregnant USM compared to the effects achieved when these drugs are administered individually. Conclusion A combination of sub-threshold doses of VGCC blocker and β2AR agonist with ANO1 antagonists potentiates relaxation of oxytocin-induced contractility and calcium flux in human USM ex vivo. Our findings may serve as a foundation for novel tocolytic drug combinations.

The dioxin regulation criteria in the agro-industrial complex of Russia

The article studies the reactions of biochemical, hematological, pathomorphological, immunological and ultrastructural changes in the organisms of laboratory animals that were subjected to chronic dioxin poisoning at threshold doses were studied. There were hold toxicological experiments on white rats of both sexes weighing 155–215 g in order to detect threshold doses. For two months, 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8- TCDD) in amounts corresponding to 1/100 and 1/200 LD 50. After each decade, some of the animals were euthanized and weighed to calculate the mass coefficient of internal organs. The obtained data comparison revealed no statistically significant changes in organ. Continued observation of animals in the experiment for up to two months, characteristic intoxication 2,3,7,8-TCDD clinical signs did not give. The correlation dependence of the minimum effective doses of 2,3,7,8-TCDD, namely 1/400 of LD50 with LD50, was determined. The obtained threshold dose of dioxin can be recommended as the basis for the normalization of dioxin in the Russian agro-industrial complex. There were determined biochemical, hematological and ultrastructural changes in the body of animals exposed to chronic poisoning of 2,3,7,8-TCDD in doses of 1/200, 1/300 of LD50. The article describes a statistically significant dependence of the respiratory activity of the liver mitochondria in laboratory animals (white rats and rabbits) on chronic poisoning with threshold doses of various degrees. Based on laboratory animals’ experiments, threshold concentrations are determined and the maximum permissible levels of dioxin in the feed of some animals are tentatively calculated.

Stimulation of Vagus By Phenylephrine Increases the Efficiency and Safety of Antidepressants and Anti-Epileptics

Background: Earlier, we discovered the possibility of potentiation of the therapeutic effects of small (threshold) doses of CNS agents by phenylephrine and adrenaline, while eliminating their side effects. However, the question of the possibility of potentiation by phenylephrine and other CNS potentiators of high therapeutic doses of CNS agents remained unstudied. This study is devoted to the research of this problem. Objective: The aim of the study was to investigate the effect of the threshold dose of phenylephrine on the antidepressant effect of amitriptyline and the anticonvulsant effect of diazepam, as well as their side sedation in high doses. Method: The experiments were carried out on the animated models of depression (Porsolt test) and epilepsy (clonic pentylenetetrazole (PTZ)-induced seizures), resistant to antidepressants and antiepileptics even at high therapeutic doses. Side sedative effect of substances was evaluated in the "open field" test. Results: We established that the stimulation of gastric vagal afferents with phenylephrine, when administered orally at threshold doses, potentiates the anticonvulsant effect of diazepam and the antidepressant effect of amitriptyline in high therapeutic doses to the maximum level that is impossible in their application by themselves, and at the same time eliminates their side sedation. Conclusion: A synergistic effect of phenylephrine and CNS drugs on the peripheral and central links of the vagal stress-protective reflex is discussed. It is assumed that the potentiation of therapeutic effect by phenylephrine and the elimination of side effects of the CNS agents occurs as a result of strengthening the vagal stress-protective reflex, eliminating the drug stress.