ORIGINAL ARTICLES
The formation of pancreatic cysts is a serious complication of acute pancreatitis, chronic pancreatitis and pancreatic injuries. Joulemetry is an integral method for evaluating the electrochemical properties of biological objects. To date, this method has not been used in the study of the electrochemical properties of the contents of pancreatic cysts. The purpose of this study was to evaluate the effectiveness of electrochemical analysis in the detection of infection in the contents of necrotic pancreatic cysts. An electrochemical study of contents of necrotic pancreatic cysts carried out on 106 patients. Group 1 included 84 patients without signs of infection of pancreatic cysts; group 2 included 22 patients with signs of infection of pancreatic cysts. The electrochemical study was conducted as follows: 10 ml of the contents of a pancreatic cyst was injected into a liquid ˛ow sensor of a joule meter, where it was exposed to a electrical current for a short period of time. The resulting data was analyzed using a diagnostic research complex. During the study of the electrochemical properties of the contents of postnecrotic pancreatic cysts by using joulemetry, it was revealed that the current work in patients of group 1 ranged from 0.92 to 18.31 mkJ (on average 5.86±5.02 mkJ), in patients of group 2 – from 19.01 to 26.3 mkJ (on average 22.32±1.92 mkJ). When evaluating the quality of the joulemetric study in determining the early signs of in˛ammation of the contents of postnecrotic pancreatic cysts, it was proved that the threshold differential diagnostic value of 19.1 mkJ provides 81.8% sensitivity of the proposed method and 80.7% specificity (AUC = 91.3) with a statistically signi˝cant difference in current work (p < 0.001).
Hypoxia negatively affcts the effctiveness of all types of anticancer therapy, in particular photodynamic therapy (PDT). In this regard, various approaches to overcome the limitations associated with hypoxia are widely discussed in the literature, one of them is the use of photosensitizers (PS) operating through the fist mechanism of the photodynamic reaction, such as methylene blue (MB). Previously, we have demonstrated that MB can have a positive effect on tumor oxygenation. In this work, we investigated the photodynamic activity of MB and a combination of MB with chlorin e6 on a tumor in vivo using a model of Ehrlich carcinoma. PDT was studied with the joint and separate administration of chlorin e6 and MB. The accumulation and localization of MB and its combination with chlorin e6 in vivo was assessed using video ˛uorescence and spectroscopic methods, and the effect of laser exposure on accumulation was analyzed. After the PDT with chlorin e6, MB and a combination of MB with chlorin e6, a good therapeutic effect and a decrease in the tumor growth rate were observed compared to the control, especially in groups with PDT with MB and with the simultaneous administration of chlorin e6 and MB. The level of tumor oxygenation on days 3 and 5 after PDT was higher for groups with irradiation, the highest oxygenation on the 5th day after PDT was observed in the group with PDT only with MB. Phasor diagrams of tumors after PDT show a deviation from the metabolic trajectory and a shift towards a longer lifetimes compared to the control tumor, which indicates the presence of lipid peroxidation products. Thus, tumor regression after PDT is associated with the direct destruction of tumor cells under the in˛uence of reactive oxygen species formed during PDT. Thus, the effectiveness of PDT with the combined use of MB and chlorin e6 has been demonstrated, and the main mechanisms of the antitumor effect of the combination of these PS have been studied.
The creation of combined nanomedicines and their controlled release under the influence of photoinduction is an actively developing branch of scientific research. This work is devoted to the development of models of solid lipid nanoparticles for a well-known antitumor drug – gefitinib in combination with a photoindicating agent – a photosensitizer from the phthalocyanine group. Nanoparticles were obtained by several methods: hot homogenization with stearic acid, sesame oil and Tween 80 and by one-step dispersion with copolymers of lactic and glycolic acids and polyvinyl alcohol. In vitro experiments when irradiating particles with a laser in the near-infrared range (about 730 nm) proved the advantage of using combined nanoparticles with gefitinib and a photosensitizer compared to monotherapy, while the activity in terms of IC50 was 5.1-8.7 times higher for gefitinib and 1.5-1.8 times for the photosensitizer.
The study aimed to investigate the bactericidal eŠcacy of high-intensity pulsed broadband irradiation in the treatment of infected wounds. An experimental study was conducted on 90 mature male Wistar rats. An infected wound model was created by contaminating with Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Animals in Group 1 received high-intensity pulsed broadband irradiation. Animals in Group 2 received traditional UV irradiation. Animals in Group 3 had their wounds cleaned with 0.1% chlorhexidine solution. By the 3rd day of treatment, animals that received pulsed high-intensity broadband irradiation showed a signifiant reduction in contamination by Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa compared to Group 3. By the 7th day of treatment, half or the majority of animals in Groups 1 and 2 showed complete decontamination of wounds concerning Staphylococcus aureus and Klebsiella pneumoniae. Most animals in Group 1 showed complete wound clearance of Pseudomonas aeruginosa. By the 10th day, nearly all animals in Group 1 demonstrated complete decontamination of wounds. Statistical analysis revealed a signifiant difference in the reduction of wound contamination with Staphylococcus aureus and Klebsiella pneumoniae by the 10th day in Groups 1 and 2 compared to Group 3. Thus, the use of high-intensity pulsed broadband irradiation of wounds reduces the degree of pathogenic microorganism contamination in a shorter time frame.
LITERATURE REVIEWS
A systematic review and meta-analysis was aimed to assess the effectiveness of palliative photodynamic therapy for unresectable malignant tumors of the biliary system in order to justify the feasibility of including photodynamic therapy (PDT) in the complex treatment of this category of patients. Publications in the databases PubMed Central, the bibliographic database of scientifi citations of the RSCI, and the Cochrane library were considered. Heterogeneity was assessed graphically using forest plots and statistically using tau2 and I2 statistics. A meta-analysis of 5-year survival revealed a statistically signifiantly longer pooled estimate of the survival period in groups where PDT was used – 339±161 days (95% CI 25-710; p < 0.001) compared to groups where PDT was not used – 83±16 days (95% CI 33-100; p < 0.001). Heterogeneity among studies was found to be statistically insignifiant (I2 = 29%, p = 0.23). A meta-analysis of the risk difference for adverse events revealed a statistically signifiantly lower risk (-0.2306; 95% CI -0.3917-0.0696; p = 0.005) of adverse events after PDT compared with the comparison group. Heterogeneity among studies was found to be statistically insignifiant (I2 = 0%, p = 0.35). There were no signifiant publication biases in either meta-analysis. The presented meta-analysis demonstrated that PDT may be the method of choice in the palliative complex treatment of patients with unresectable cholangicarcinomas, increasing the ˝ve-year survival of patients along with the absence of increased risks of postoperative complications in comparison with other methods of palliative surgical treatment.
Features of the expression of membrane importers of 5-ALA, as well as transporters involved in the removal of photoactive precursors of protoporphyrin IX (PPIX) (uro-, copro- and protoporphyrinogens), may cause differences in the effectiveness of photodynamic therapy of malignant neoplasms using 5-aminolevulinic acid (5-ALA). Increased expression of ALA transporters is associated with an increase in the intensity of PPIX synthesis. When the expression of PPIX exporters increases, there is a decrease in PPIX concentration. The review describes the main transporters of 5-ALA, uro-, copro- and protoporphyrinogens, provides data on their expression in various tissues, and discusses the possibility of predicting the effectiveness of photodynamic therapy considering the expression of the corresponding transport proteins in malignant tissues.