PARP inhibitors are a new area in the treatment of breast cancer

The paper considers the use of poly(ADP-ribose)-polymerase inhibitors in therapy for breast and ovarian cancer. Particular attention is given to drugs, such as olaparib and BSI-201. It is noted that the emergence of drugs of this class, of course, holds great promise for using remedial measures and gives certain hopes for their optimization

Atypical hyperplasias of the breast

The paper describes different types of atypical hyperplasia of the breast. It analyzes numerous works dealing with the evaluation of atypical ductal and lobular hyperplasias as a risk factor for breast cancer. The similar analysis has been also carried out in a cohort of women with a family history. The current capabilities of visual, cytological, morphological, and molecular biological diagnosis of atypical hyperplasias are considered. Modern-day guidelines for the treatment policy and monitoring of treated patients are given. The role and place of different chemoprevention options for this cohort of patients are considered. Whether preventive surgery may and should be performed particularly in a cohort of women with a family history is determined

ANALYSIS OF THE RESULTS OF NEODJUVANT TREATMENT IN PATIENTS WITH CONSIDERATION FOR THE IMMUNOPHENOTYPICAL FEATURES OF BREAST CANCER

The efficiency of neoadjuvant chemotherapy is directly related to the expression of CD95 (FAS/APO-1) apoptosis receptor on cancer cells, which is confirmed with the pathomorphism and changes of CD95-positive cells during neoadjuvant chemotherapy (the most effective CAF regimen is cyclophosphan, doxorubicin, and 5- fluorouracil)

Composition based on aluminum oxide and polydimethylsiloxane matrix for enhancing drug targeting

Methodological approaches developed at Research Institute of Clinical and Experimental Lymphology for a number of years allow formulating the importance of embedding active pharmaceutical ingredients (API) in the structure of porous carriers (sorbents). The composition of the carrier and API is an enteral system for prolonged dosing of pharmacological agents, which allows providing a specific pharmacological effect and safety of use. The pores of the media (sorbents) act as containers for API. This is especially important for rapidly absorbed drugs, which include, for example, lithium preparations that are used in narrow concentration limits due to their side effects. At the moment, an innovative technology for creating new medicines with an improved combination of efficiency and safety (pharmacological upgrade) has been developed and implemented. The essence of the technology is to create a composition of aluminum oxide and polydimethylsiloxane (matrix) and an active pharmacological ingredient (API). A study of two drugs based on matrix / lithium citrate and matrix / melatonin showed continued specific pharmacological activity of API, better pharmacokinetics, and better safety parameters. The matrix of aluminum oxide and polydimethylsiloxane provides an upgrade of the pharmacological properties of drugs for the dosed and safe delivery of API to the zone of their therapeutic effect

Lipodystrophy at the insulin injection sites: current trends in epidemiology, diagnostics and prevention

Lipodystrophy at the injection sites is most common local complication of insulin therapy. The history of its study started in 1926, when first cases of lipoatrophy at the sites of insulin injections were described. As we moved to human insulin and insulin analogues, immune mediated atrophic form of lipodystrophy has been replaced by hypertrophic one, which reflects anabolic and mitogenic effect of insulin. Lipohypertrophy at the injection sites is detected by physical examination in 40-70% of insulin-treated subjects. The detection efficiency depends on health care provider`s skills. Therefore, training of medical doctors and nurses in physical examination of injection sites seems to be reasonable. In recent years, ultrasound was introduced for diagnostics of insulin-induced lipohypertrophy. The method is more sensitive compared to palpation; ultrasound-verified lipohypertropthy was detected in more than 80% of cases. In patients with wide-spread lipohypertrophy ultrasound can be used to find suitable sites for injections (“ultrasound injection map”). Strain sonoelastography and 3D-power Doppler ultrasound can be used for quantitative estimation of rigidity and vascularization of lipohypertrophy. Both MRI and infrared images are considered as promising diagnostic tools. In a number of studies, it has been shown that the presence of lipohypertrophy is associated with high HbA1c levels, enhanced glycemic variability, «unexplained» hypoglycemia, and increased insulin doses. Thereby, lipohypertrophy aggravates the diabetes-related costs. The main risk factor for lipohypertrophy is inappropriate injection technique, including the lack of the site rotation, injections into lipodystrophic lesions, small injection area, reuse or excessive length of the needles. Accordingly, training patients in the injection technique is the basis for prevention of complication. The cessation of injections in lipohypertrophy areas and regular site rotation is essential for adequate titration of insulin dose and achievement of glycemic targets

The effect of silver-containing sorbent on red blood cells during hemosorption: an <i>in vitro</i> study

The aim of the study was to investigate the influence of the original porous silver–containing sorbent on the morphofunctional parameters of red blood cells during in vitro hemoperfusion. Material and methods. Donor blood was perfused through glass columns filled with a sorbent based on porous aluminum oxide, polydimethylsiloxane and silver nanoclusters and a sorbent without silver. The effect of a silver-containing sorbent on the change in morphofunctional parameters of red blood cells after perfusion through sorbents was determined by scanning flow cytometry. Results and their discussion. Due to the uniformity of the distribution of silver (0.1 %) over the sorbent granules, the parameters of the porous structure – the specific surface area and pore volume – practically do not change compared to the sorbent without silver. Morphological parameters of original donor blood and after hemoperfusion are within the norm. The functional parameters are also normal, although the introduction of silver in to the sorbent slightly increases the number of active band 3 (B3) proteins on erythrocyte membranes, both in comparison with the donor red cell mass as a control and in comparison with the sorbent without silver. There is also an increase in the ultimate extensibility of the erythrocyte membrane compared to the original blood (2.2 times) and the sorbent without silver (1.4 times). Conclusions. A sorbent modified with silver and a sorbent without silver does not have a damaging toxic effect on the morphofunctional parameters of blood under perfusion conditions. The mechanisms affecting the indicators of the ultimate extensibility of the erythrocyte membrane after blood perfusion through a silver-containing sorbent require further research

Insulin-induced lipohypertrophy: clinical and ultrasound characteristics

Background: Lipohypertrophy is primary dermal complication of insulin therapy. The data on the prevalence of lipohypertrophy in diabetic subjects are inconsistent, that may be due to the lack of sensitivity and subjectivity of palpation as diagnostic technique. Meanwhile, the reliability of lipohypertrophy detection can be increased by ultrasound. Aims: to compare clinical and ultrasound characteristics and to determine the risk factors of insulin-induced lipohypertrophy in diabetic subjects. Materials and methods: We observed 82 patients, including 26 individuals with type 1 diabetes and 56 subjects with type 2 diabetes. Duration of insulin therapy varied from 3 months to 37 years (median 14 years). The sites of insulin injections were assessed by palpation and ultrasound. Visualization protocol included gray-scale densitometry, strain elastography, and 3D Doppler power ultrasound. Scaled evaluation of ultrasound sings was applied. Insulin injection technique was assessed by questionnaire. Serum levels of insulin antibodies were determined by ELISA. Results: Lipohypertrophy was revealed by palpation and ultrasound in 57 and 80 patients (70% and 98%) respectively. Total lipohypertrophy area, acoustic density and total ultrasound score showed weak positive correlations with daily insulin dose (r=0.3, r=0.3 and r=0.35, respectively, all p0.006). Patients receiving insulin analogues had smaller area of abdominal lipohypertrophy than those on human insulin (p=0.03). A positive correlation was found between abdominal lipohypertrophy area and mean postprandial glucose (r=0.35, p=0.001). A rare needle change and injections in lipohypertrophy sites were the most common deviations in insulin injection technique (70 and 47 subjects, 85% and 53% respectively). The levels of insulin antibodies showed no association with lipohypertrophy parameters. Conclusions: Patients with type 1 and type 2 diabetes demonstrate high prevalence of lipohypertrophy in insulin injection sites. Ultrasonography is more sensitive method of diagnostics of lipohypertrophy compared with palpation. Insulin-induced lipohypertrophy is associated with errors in injection technique and higher insulin doses

Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide

Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76)

STUDYING THE POSSIBLE MUTAGENIC PROPERTIES OF NEW MEDICINE ON THE BASIS OF COMPLEX LITHIUM CITRATE, ALUMINUM OXIDE AND POLYMETHILSILOXANE

Aim of the study was to investigate the possible mutagenic properties of a new drug based on a lithium-containing substance – a complex of lithium citrate, polymethylsiloxane and aluminum oxide. Material and methods. Methods for testing mutagenicity using chromosomal aberrations in the bone marrow cells of CBA mice and somatic recombination in Drosophila melanogaster were used. Results. It was shown that a single intragastric administration of drug at a dose of 5000 mg/kg and a fivefold course of administration at a dose of 400 mg/kg to CBA mice did not increase the level of cytogenetic disorders in bone marrow cells. The study of the lithium complex drug in a somatic mosaicism test revealed that the preparation at a dose of 2000 mg/kg does not increase the frequency of mutations in Drosophila melanogaster. Conclusion. A single intragastric administration of the studied drug at a dose of 5000 mg/kg and its course administration (400 mg/kg × 5) do not increase the level of cytogenetic disorders in the bone marrow cells of CBA mice. In the somatic recombination (mosaicism) test system on D. melanogaster, no increase in the appearance of mutant setae and spots on the body and head was observed when using yellow and singed markers. The results of the study indicate that the studied drug does not have mutagenic properties

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3