The search for new anticonvulsants in a group of (2,5-dioxopyrrolidin-1-yl)(phenyl)acetamides with hybrid structure - synthesis and in vivo/In vitro studies

Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a focused series of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant properties. We applied an optimized coupling reaction yielding several hybrid compounds that showed broad-spectrum activity in widely accepted animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model in mice. The most potent anticonvulsant activity and favorable safety profile was demonstrated for compound 30 (median effective dose (ED50) MES = 45.6 mg/kg, ED50 6 Hz (32 mA) = 39.5 mg/kg, median toxic dose (TD50) (rotarod test) = 162.4 mg/kg). Anticonvulsant drugs often show activity in pain models, and compound 30 was also proven effective in the formalin test of tonic pain, the capsaicin-induced pain model, and the oxaliplatin (OXPT)-induced neuropathic pain model in mice. Our studies showed that the most plausible mechanism of action of 30 involves inhibition of calcium currents mediated by Cav1.2 (L-type) channels. Importantly, 30 revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of CYP3A4, CYP2D6, and CYP2C9 isoforms of cytochrome P450, compared to reference compounds. The promising in vivo activity profile and drug-like properties of compound 30 make it an interesting candidate for further preclinical development

The potential of naproxen and its derivatives in inhibiting the processes of initiation, promotion and progression of cancerogenesis

Introduction: Naproxen is a non-steroidal anti-inflammatory drug mainly used to treatinflammation, pain, and fever of various etiology. Scientific studies conducted over the lastfive years have shown, that its introduction significantly influenced neoplastic processes inthe in vitro and in vivo studies carried out within cell cultures and animal models.Aim of the study: Our aim was to review the theses, extract and present the influence ofnaproxen and its derivatives in signaling pathways involved in the initiation, promotion andprogression of cancer as well as to indicate potential directions for further research.Methods and materials: We have reviewed the theses in the bibliographic PubMed database,using the keywords: „naproxen”; „naproxen derivatives”; „cancer”; „cancer treatment”„cancer prevention”.Results: In addition to the well-known mechanism of inhibiting COX, there are scientificproofs of the activity of naproxen against other molecules, such as PI3-K(phosphatidylinositol 3-kinase), GSK-3β (glycogen synthase kinase-3β), NFκB (nucleartranscription factor κB), MMP ( metalloproteinases), NO (nitric oxide) involved in neoplasticprocesses.Conclusion: Conclusions drawn from the analysis of specific molecular activities of naproxenand its derivatives against neoplastic processes are promising. However, more preclinicalresearch is needed to confirm the effectiveness, practical applicability and to assess the sideeffects of the therapy, before starting the clinical trials in humans

Effect of fasting mimicking diet on cardiovascular risk factors

Introduction: Cardiovascular diseases (CVDs) remain major problem in modern medicine. According to World Health Organization they are the leading cause of death. Despite increased awareness about impact of healthy lifestyle,  mortality still remains on high level. Cardiovascular diseases requires multidisciplinary treatment. One of those aspects is determinate an appropriate diet.   Purpose: The aim of this systemic review is to collect, evaluate and summarize the information on fasting mimicking diets and it is effect on therapy and prevention in cardiovascular diseases. Material and methods: Analysis and review of available literature. The search of articles in popular scientific databases such as PubMed, Google Schoolar WHO database State of knowledge: Risky behavior include unhealthy diet, tobacco use, physical inactivity, alcohol abuse. Those behaves lead obesity, raised blood pressure, hyperglycemia, dyslipidemia. Those factors have significant impact on the increase of cardiovascular diseases in the population. Fasting and calorie restriction are becoming more and more popular. Results: Many studies indicate that fasting mimicking diet can prevent from excessive fat accumulation, obesity, diabetes, dyslipidemia, hypertension As a result it decreases probability of cardiovascular diseases. Those diets not only support weight loss, but also can help maintain good health  and extend lifespan

Multipotential use of an old drug, as a new solution for anticancer therapy and multidrug-resistant urinary tract infections

Introduction        Nitroxoline (NTX) is a well-known chemotherapeutic agent that has been used to treat urinary tract infections since the 1960s. Today, the incidence of multidrug-resistant (MDR) bacterial strains is on the rise worldwide. This has resulted in repurposing, whereby during the ongoing research on nitroxoline, the possibility of its wide use has been demonstrated, not only in treatment against resistant pathogens, but also potential broad anti-cancer applications. Aim of the study The purpose of our work was to review scientific articles and show the multi-potential - anti-pathogenic and anti-tumor use of nitroxoline. Methods and materials We reviewed the English-language literature in the PubMed database, using the key words: „Nitroxoline”, „Nitroxoline cancer”, „Nitroxoline antibacterial use”   Results Analysis of studies has shown that nitroxoline, currently used in benign urinary tract infections, is also applicable in the treatment of urinary tract infections caused by multidrug-resistant bacteria (MRD). It is also active against drug-resistant fungi and mycobacteria. Repurposing has also demonstrated the anticancer effects of nitroxoline through inhibition proliferation, induction apoptosis of tumor cells and other mechanisms, making it likely that nitroxoline will be used in cancer treatment regimens in the future. Conclusion Nitroxoline has found widespread use in the treatment of urinary tract infections caused by multidrug-resistant bacteria (MRD) and by strains of resistant fungi, which in today's world are spreading and increasing their drug resistance. Repurposing has shown promising anticancer activity of nitroxoline in the treatment of urinary tract cancers and more. The data supporting the effects of nitroxoline seem promising, suggesting the rationale for future clinical trials to further our understanding of the exact mechanisms of action and use of nitroxoline in oncology treatment

DAA - directly acting antivirals - as a new, more efficient solution of the chronic hepatitis C treatment and theirs various application.

Introduction Cirrhosis is a condition in which the liver becomes fibrotic following damage to the liver and transforms the architecture of the organ into regenerative nodules. The disease is caused 30% by HCV infection, resulting in a risk of severe complications and death. Since the use of direct-acting antivirals ( DAAs) for the treatment of chronic HCV, sustained virological response (SVR) rates have begun to increase, even in treatment-resistant cases. Studies have also shown that DAAs may have applications in other viral diseases and even In the treatment of breast cancer.   Aim of the study The purpouse of our study was to review scientific articles to show the efficiency and potential use of DAAs in the treatment of chronic HCV, and to identify possible directions for further research.   Methods and materials We reviewed the English literature in the PubMed, using the key words: "simeprevir" ; "sofosbuvir" ; "velpatasvir" ; "telaprevir" ; "chronic hepatitis C".   Results Studies have shown that the therapeutic regimens currently being designed with (DAAs) offer the possibility of treating almost the entire population with hepatitis C, while reducing side effects of interferon therapy such as increased AST, ALT activities, diarrhoea, vomiting, nausea and  depression. They remain effective and tolerable, regardless of the stage of cirrhosis and associated serious co-morbidities. Analysis of studiem shows, that DAAs also show efficacy against other disease such as breast cancer, MRSA infections, SARS-CoV-2 or flavivirus infection.   Conclusion All (DAAs) are effective in the treatment of patients with HCV, including cirrhosis. They result in significant improvements in prognosis and clinical outcomes. Promising results have been obtained in published data on the effect of DAAs against disease entities other than HCV, suggesting the rationale for future clinical trials to further the hypothesis of the increased potential of these drugs

Gliflozins and their beneficial hypoglycaemic effect profile and prevention of cardiovascular complications in patients treated for type II diabetes mellitus

Introduction: Diabetes mellitus type 2 (DM2) is a population disease, it is predicted that by 2030 the DM2 will affect 7% of the population. Patients due to progress of the disease in case of micro and macro angiovascular changes develop organ complications mainly in terms of cardiovascular disease (CV). Sodium-glucose cotransporter 2 (SGLT2) inhibitors are relatively new group of drugs that apart from the hypoglycemic effect, also have other beneficial effects. Due to the scale and importance of the problem of diabetes complications researchers from around the world are working on its solution.   Aim of the study: The aim of this study was to present the effects of SGLT2 inhibitors on cardiovascular complications in DM2 patients.   Methods and materials We reviewed the literature contained in the PubMed database, using keywords: „Diabetes type 2”; „SGLT2 inhibitors”; „Cardiovascular disease”; „Heart failure”   Results: In addition to their hypoglycaemic effects, SGLT2 inhibitors have also been shown to have beneficial effects on the CV system. Studies have shown that in DM2 patients treated with gliflozins, the risk of hospitalisation for heart failure decreased by 35% and the risk of death from cardiovascular causes by 38%. Retrospective studies have been carried out in which the efficacy of all drugs in the group in question, and not just individual substances, has been proven. In clinical experiments, phlazines were confirmed to reduce the risk of CV complications, including heart failure, myocardial infarction, angina, stroke or atrial fibrillation.   Conclusions: SGLT2 drugs reduce the risk of cardiovascular complications and reduce hospitalisations for heart failure in patients with DM2. Future studies should seek to determine at what stage treatment should be implemented to maximise the resulting benefits to the patient

New uses for vitamin C, and its versatile, pleiotropic antioxidant action. - Treatment of neoplasms, skin diseases, bone diseases and stimulation of the immune system

Introduction: Vitamin C (Vit C) is an organic chemical compound from the group of unsaturated polyhydroxy alcohols. It influences physiological processes such as the facilitation of iron absorption, hormone and carnitine synthesis, and is also involved in epigenetic processes. It is a vitamin, which means that it must be provided in food. It is also an antioxidant used as a food additive. In recent times, its pleiotropic use has been proven in the treatment of immune deficiencies, the treatment of skin diseases, bone diseases and may also be used in new cancer treatment regimens.   Aim of the study: To review the current literature on the use of vitamin C in various fields of health and science.    Materials and Methods: We reviewed the literature available in PubMed, using the key words: "vitamin C"; "ascorbid acid"; "cancer treatment"; "vitamin C immune function".   Results: Vitamin C has pleiotropic effects on the human body, both through its effects on cells and tissues and through its antioxidant mechanisms and regulation of gene expression. It has been shown to be a key antioxidant with anti-inflammatory and immune system supportive effects. Its effect of slowing down skin photo-ageing by reducing the amount of metalloproteinases induced by reactive oxygen species has been noted in the literature. Vitamin C has been shown in studies to reduce the risk of osteoporosis due to its osteoclast inhibitory properties. Beneficial effects of high-dose intravenous infusions have also been demonstrated in the treatment of cancer, as well as about reducing organ failure and vascular damage in patients with ARDS and sepsis.   Summary: The versatile action of vitamin C has made it the subject of intense research. However, the reports in the literature to date on its use require further studies on larger groups of people to confirm its effects

Palliative cancer patients pain reduction methods during opioid epidemic era

Introduction: Opioids are the most commonly used medication in palliative cancer pain treatment due to their proven effectiveness. However, modern anti-pain treatment concentrates not only on analgesics, but simultaneously on the detection of conditions affecting and intensifying pain sensation. Many studies have shown potential of other, non-opioidal palliative cancer pain treatment with additional positive effect on patient’s general quality of life. Aim of the study: The purpose of our review is to introduce the issue of the use of opioids and draw attention to other non-opioidal pain reduction methods as well as to indicate directions for further potential researches. Methods and materials:  We have reviewed the literature available in the PubMed, Google Scholar, Science Direct database using the keywords: „cancer patients and opioids”; „pain and cancer”; „chronic pain”; „palliative cancer”. We excluded abstracts, comments, and non–English language articles. Results: The methods outlined in this review will not affect pain reduction to the same extent as opioids, but they offer a chance to reduce it to a level that allows patients to maintain a normal life. In the light of opioid epidemic era literature shows new approaches to treating pain such as analgesics, including antidepressants, anticonvulsants, Vitamins, cannabis and nonpharmacological methods and showing their potential for wider use in palliative cancer patients treatment. Conclusion: Besides opioids, there are many factors that affect pain reduction, however, their analgesic potential require additional studies on larger groups of patients

Contrast-induced nephropathy (CIN) - epidemiology, risk factors and prevention

Introduction: Contrast-induced nephropathy is one of the most serious adverse effects of radiocontrast agents usage. It is currently listed in the literature as the third most common cause of iatrogenic acute kidney injury. Aim of the study: The aim of this study is to provide an overview of the extent, severity and prevention of CIN. It is to shed a broader light on this disease entity and be a helpful resource in the future for other clinicians struggling with CIN. Methods and materials: A literature review was conducted using the PubMed database, using the keywords: "contrast-induced nephropathy"; "acute kidney injury"; "contrast media". Results: Pathogenesis of CIN is not entirely clear. There are many risk factors being e.g. diabetes, chronic kidney disease, advanced age (patients over 75 years old). Prevention methods include restricting contrast volume to a minimum, balancing the patient's volaemia before contrast administration or perioperative saline hydration to normalise volaemia. Conclusion: CIN is a significant health problem, which can be a life threat. Despite the fact that the exact pathogenesis of the condition still remains unknown, the CIN prophylaxis becomes more and more effective due to better recognition of risk factors and the usage of adequate prevention measures appropriate to the patients' condition. More studies, with larger test groups, are needed to better define both the pathomechanism of contrast-induced acute kidney injury and new, more effective ways of prevention and treatment of this condition