Participation of oxidative stress in selected diseases in the light of the latest research

Disturbances in the balance between the production and accumulation of reactive oxygen species and the proper functioning of antioxidant systems are the source of the phenomenon called oxidative stress. In physiological conditions in the human body, the conditions of the aforementioned balance are maintained, however, in pathological conditions related to exposure to reactive oxygen species or also in the course of diseases, cellular homeostasis may be disturbed. The role of oxidative stress in the pathogenesis and course of diseases affecting many organs has been known for many years. Atherosclerosis, arterial hypertension classified as cardiovascular diseases or neurological diseases such as Parkinson's disease and Alzheimer's disease are just some examples of diseases in which the role of oxidative stress has been known for years. The discovery of new technologies, as well as the sometimes not fully understood pathogenesis of many diseases, is the basis for further research on the impact of reactive oxygen species on pathological processes occurring during the development of the disease and phenomena occurring during treatment. At present, numerous studies and clinical experiments are being carried out, the subject of which is related to the influence of reactive oxygen species on the pathogenesis, clinical picture and treatment of various diseases. Due to the fact that neoplastic diseases are expected to become the most common cause of death, the generation of oxidative stress in neoblastic cells may, on the contrary, become the basis of therapy. The purpose of this article is to review the latest scientific reports on the role of oxidative stress in the pathogenesis and course of selected diseases, i.e. neurological diseases (including Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease), cardiovascular diseases (including atherosclerosis arteries, arterial and pulmonary hypertension), lifestyle diseases (diabetes and osteoporosis) and cancer, also in the aspect of therapy with compounds that generate oxidative stress

Malignant melanoma: epidemiology, pathogenesis, diagnostics and innovative therapeutic methods

Melanoma is the most common cause of death among people with skin cancer, and its development is most often associated with excessive exposure to ultraviolet radiation and predisposing genetic factors. Early detection of melanoma significantly reduces mortality in both the short and long term. Unfortunately, this cancer has the ability to quickly reach the malignant phase and metastasize to other organs. The typical treatment for melanoma is surgical resection, but over the last few years significant progress has also been made in the field of systemic therapies, which has led to a noticeable improvement in survival in patients with metastases. The article summarizes information about modern therapeutic methods used in patients with melanoma. Drugs belonging to BRAF kinase inhibitors: vemurafenib and dabrafenib are currently the first-line therapy for advanced melanomas with a confirmed BRAF gene mutation. Modern therapeutic strategies that have revolutionized the treatment of melanoma also include immunotherapy. By blocking inhibitory checkpoints of the immune system, it is possible to generate an anti-cancer response alone or in synergy with other types of therapy. These drugs target molecules that are pathologically overexpressed in melanoma, such as PD-1 or CTLA-4. Intralesional agents, such as oncolytic viruses, can also induce immune stimulation to destroy cancer cells. The only drug of this type registered so far for the treatment of melanoma is talimogene laherparepvec, which uses a genetically modified herpes simplex virus type 1. The possibility of individually tailored treatment to the patient is created by CAR-T therapy, which involves collecting tumor-infiltrating T lymphocytes from the patient, modifying them to obtain a receptor that specifically recognizes melanoma cells, and then multiply and introduce it into the patient's body. Recent findings have shown higher success rates with combinations of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Despite the success of modern systemic therapy, many melanoma patients do not respond to treatment or develop drug resistance, which leads to the constant need to look for new solutions in the fight against this cancer

Nicotine–melanin interaction

BACKGROUND The available literature suggests that nicotine may accumulate in human tissues containing melanin, which increases the biosynthesis of this pigment. Studies conducted on the interaction between nicotine and melanin do not explain the impact of this binding on the metabolism and distribution of nicotine, level of dependence, effectiveness of smoking cessation therapies and potential adverse effects of nicotine. The role of these interactions may be important for people with a high degree of skin pigmentation. It is necessary to answer questions concerning the nature of nicotine–melanin interaction as well as the effect of nicotine on human cells, tissues and organs containing melanin pigment. The aim of this study was to examine the ability of nicotine to bind to synthetic melanin and to evaluate the kinetics and the nature of these interactions. MATERIAL AND METHODS Nicotine–melanin complexes were analyzed by use of the Scatchard method. The amounts of nicotine bound to melanin were determined spectrophotometrically. RESULTS It has been demonstrated that nicotine forms complexes with melanin. The amounts of nicotine bound to melanin increase with rising initial concentrations and prolongation of incubation time. For the studied complexes, two classes of independent binding sites with association constants K1 = 2.44 × 104 M-1 and K2 = 7.72 × 102 M-1 have been found. CONCLUSIONS The obtained results indicate the possible role of melanin in side effects of nicotine and in smoking cessation therapies effectiveness among people with high levels of pigmentation.WSTĘP Dostępna literatura sugeruje, że nikotyna może kumulować się w ludzkich tkankach zawierających melaninę, co powoduje zwiększenie biosyntezy tego barwnika. Dotychczasowe badania nad oddziaływaniem nikotyny z melaniną nie wyjaśniają wpływu wiązania na metabolizm i dystrybucję nikotyny, poziom uzależnienia, zdolność do zaprzestania palenia czy zwiększenie ewentualnych działań niepożądanych nikotyny. Rola tych oddziaływań może mieć duże znaczenie w przypadku osób o wysokim stopniu pigmentacji skóry. Odpowiedzi wymagają pytania dotyczące charakteru wiązań między nikotyną a melaniną oraz zmian, jakie nikotyna może wywierać w komórkach, tkankach i narządach ludzkiego ciała, w których występuje melanina. Celem badań była ocena zdolności nikotyny do wiązania się z melaniną syntetyczną, a także ocena kinetyki wiązania i trwałości powstałych kompleksów. MATERIAŁ I METODY Kompleksy nikotyna–melanina oceniano metodą Scatcharda. Ilość nikotyny związanej z melaniną wyznaczono techniką spektrofotometrii UV-VIS. WYNIKI Wykazano, że nikotyna tworzy kompleksy z melaniną. Ilość nikotyny związanej z melaniną wzrasta wraz ze wzrostem stężenia początkowego oraz z wydłużaniem czasu inkubacji. Dla badanych kompleksów stwierdzono występowanie dwóch klas niezależnych miejsc wiążących o wartościach stałych trwałości K1 = 2,44 × 104 M-1 oraz K2 = 7,72 × 102 M-1. WNIOSKI Uzyskane wyniki wskazują na możliwą rolę melaniny w działaniach niepożądanych nikotyny oraz w problematyce zaprzestania palenia u osób o wysokim stopniu pigmentacji

Melanin – from melanocyte to keratinocyte, that is how melanin is transported within the skin

The article presents classifi cation, functions of melanins together with maturation stages and transport mechanisms of melanosomes from melanocytes to keratinocytes. Melanins are macromolecular pigments, occuring in the plants, animals and fungi kingdoms. Melanins can be classifi ed into three groups: eumelanin, pheomelanin and allomelanin. They are widely distributed in organism and are responsible for the colour of eyes, skin, hair, feathers and coats. Protective role of melanins is connected with absorbing of UV radiation and scavenging of free radicals. They can also interact with drugs, infl uencing therapeutic and toxic eff ects. Melanins are synthesized in melanocytes, in lysosome-related organelles – melanosomes. Melanosomes mature through four morphologically distinct stages. In melanocytes, they move rapidly fi rstly along microtubules and secondly along actine fi laments to the end of dendrites. Next, melanosomes are transferred to keratinocytes, where determine colour of skin and protect against ultraviolet radiation.W artykule przedstawiono podział i funkcje melanin oraz etapy dojrzewania i transportu melanosomów z melanocytów do keratynocytów. Melaniny są wielkocząsteczkowymi barwnikami szeroko rozpowszechnionymi w przyrodzie. Można wśród nich wyróżnić eumelaninę, feomelaninę i allomelaninę. Pełnią one wiele ważnych biologicznych i biochemicznych funkcji. Odpowiadają za kolor oczu, skóry, włosów, a także sierści i piór, ponadto chronią komórki przed szkodliwym wpływem promieniowania UV i wolnych rodników. Mogą także oddziaływać z cząsteczkami leków, wpływając na ich skuteczność i toksyczność. Biosynteza melaniny zachodzi w wyspecjalizowanych komórkach barwnikowych – melanocytach. Za proces melanogenezy odpowiedzialne są melanosomy należące do grupy organelli komórkowych związanych z lizosomami. Powstają one w kilkuetapowym procesie z endosomalnych pęcherzyków, które dojrzewając przechodzą przez cztery różne stadia morfologiczne. Dojrzałe melanosomy są transportowane z obszaru okołojądrowego do wypustek dendrytycznych melanocytów kolejno za pośrednictwem mikrotubul, a następnie fi lamentów aktynowych. Zgromadzone w wypustkach melanocytarnych melanosomy są transportowane do otaczających keratynocytów, gdzie determinują zabarwienie skóry oraz pełnią funkcję ochronną przed promieniowaniem UV

Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms

Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells

Synthesis and Anticancer Activity of Indole-Functionalized Derivatives of Betulin

Pentacyclic triterpenes, including betulin, are widespread natural products with various pharmacological effects. These compounds are the starting material for the synthesis of substances with promising anticancer activity. The chemical modification of the betulin scaffold that was carried out as part of the research consisted of introducing the indole moiety at the C-28 position. The synthesized new 28-indole-betulin derivatives were evaluated for anticancer activity against seven human cancer lines (A549, MDA-MB-231, MCF-7, DLD-1, HT-29, A375, and C32). It was observed that MCF-7 breast cancer cells were most sensitive to the action of the 28-indole-betulin derivatives. The study shows that the lup-20(29)-ene-3-ol-28-yl 2-(1H-indol-3-yl)acetate caused the MCF-7 cells to arrest in the G1 phase, preventing the cells from entering the S phase. The performed cytometric analysis of DNA fragmentation indicates that the mechanism of EB355A action on the MCF-7 cell line is related to the induction of apoptosis. An in silico ADMET profile analysis of EB355A and EB365 showed that both compounds are bioactive molecules characterized by good intestinal absorption. In addition, the in silico studies indicate that the 28-indole-betulin derivatives are substances of relatively low toxicity

The role of protective agents in pharmacotherapy- assessment of patients awareness

SUBJECT OF THE STUDY: The use of medication is associated with the risk of side effects. In the view of the fact that the consumption of Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics is growing constantly, it is necessary to apply appropriate protection strategies to prevent side-effects of those drugs. AIM OF THE STUDY: The aim of the study is to asses patients' knowledge about protective agents: drugs that reduce the production of hydrochloric acid from the group of proton pump inhibitors and probiotics in the terms of effectiveness and safety of, respectively, inflammations and the bacterial infections pharmacotherapy. MATERIAL AND METHODS: The research was carried out since October 2018 to February 2019 on the random group of people from Poland, using an original, anonymous questionnaire. The data was collected via Internet and direct contact with the respondents participating classes at the University of Third Age of the Medical University of Silesia. The statistical analysis of the collected results was performed with the use of Microsoft Excel 2010. RESULTS: Almost everyone of the respondents (about 95.0%) think that they understand the concept of a protective agents. Many of them only associates them with antibiotic therapy, not being aware of the broader meaning of this concept. 82.0% of respondents believe that they know the concept of a probiotic, but as many as 64.6 % of patients mistakenly think, that probiotics protect the stomach. About 50.0% of people are aware of the need to protect the stomach with chronic Nonsteroidal anti-inflammatory drugs therapy. CONCLUCIONS: The obtained results show that patients have basic information about gastro-enteroprotective agents (including drugs that reduce the production of hydrochloric acid from the group of proton pump inhibitors and probiotics) however their knowledge is still insufficient to guarantee the effectiveness of therapy. The further education is necessary, which could be improved by introducing the Pharmaceutical Care.PRZEDMIOT BADAŃ: Stosowanie każdego rodzaju leków wiąże się z ryzykiem wystąpienia działań niepożądanych. W świetle rosnącego spożycia leków przeciwbólowych i antybiotyków konieczne staje się stosowanie właściwych strategii ochronnych, zapobiegających ubocznym skutkom działania tych leków. CEL BADAŃ: Celem pracy jest zbadanie wiedzy pacjentów na temat preparatów osłonowych, w szczególności leków zmniejszających produkcję kwasu solnego z grupy inhibitorów pompy protonowej oraz probiotyków. MATERIAŁ I METODY: Badanie przeprowadzono od października 2018 do lutego 2019 na losowej grupie 582 mieszkańców Polski za pomocą autorskiego, anonimowego kwestionariusza ankiety. Analizę statystyczną zebranego materiału, wykonano za pomocą programu Microsoft Excel 2010. WYNIKI: W badaniu 94,5% ankietowanych zadeklarowało, że rozumie pojęcie preparatu osłonowego. Duży odsetek grupy badanej wiąże je jedynie z antybiotykoterapią, nie mając świadomości szerszego znaczenia tego pojęcia. 82,0% respondentów uważa, że zna pojęcie probiotyku, jednak aż 64,6% z nich niewłaściwie zastosowałoby probiotyk jako osłonę żołądka. Niespełna 50,0% osób ma świadomość konieczności ochrony żołądka przy przewlekłej terapii lekami z grupy niesteroidowych leków przeciwzapalnych. WNIOSKI: Przeprowadzone badanie wykazało, że ankietowani posiadają podstawową wiedzę na temat preparatów osłonowych jednak nie jest ona wystarczająca, by w każdym przypadku zapewnić bezpieczeństwo i skuteczność terapii. Konieczne jest zatem edukacja pacjentów poprzez wdrożenie szeroko dyskutowanej obecnie Opieki Farmaceutycznej