Oxidative stress is implicated in the pathogenesis of different human diseases: Alzheimer, Parkinson, Huntington, amyotrophic lateral sclerosis (Lou Gehrig's disease), Down's syndrome, atherosclerosis, vascular disease, cancer, diabetes mellitus type 1 and type 2, age - related macular degeneration, psoriatic arthritis. The aim of current study is to summarize the scientific evidences for the antioxidant and neuroprotective activity of Galantamine and some of its derivatives. Galantamine is a scavenger of reactive oxygen species and causes neuroprotective effect by lowering the oxidative neuronal damage, through the following pathways: 1) prevention of the activation of P2X7 receptors; 2) protection of mitochondrial membrane potential; 3) pre - vention of the membrane fluidity disturbances. Another mechanism is the decreasing of the overproduction of reactive oxygen species, a result from the increasing of acetylcholine level due to: 1) acethylcholinesterase inhibition; 2) allosteric potentiation of α7 - subtype of nicotinic acetylcholine receptors. A close relationship between acethylcholinesterase inhibition and reduced oxidative injury is observed. Through allosteric potentiation of the α7 - subtype of nicotinic acetylcholine receptors, the drug leads to induction of phosphorylation of serine - threonine protein kinase, stimulates phosphoinositide 3 - kinase and elevates the expression of protective protein Bcl - 2. By activation of these important neuroprotective cascades, Galantamine exerts neuroprotection against a variety of cytotoxic agents (β- amyloid peptide, glutamate, hydrogen peroxide, oxygen and glucose deprivation). The new trend in therapy of Alzheimer's disease will be the investigation and application of compounds such as Galantamine derivatives, which possess acethylcholinesterase and γ- secretase inhibitory activity and antioxidant properties.
The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to toxicity. The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. The literature data show that the strategies for the development of platinum anticancer agents and bypassing of resistance to Cisplatin derivatives and their toxicity are: combination therapy, Pt IV prodrugs, the targeted nanocarriers. The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents—Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors—Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs—Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity.
Abstract:In modern times in all age groups energy supplements containing different amounts of Caffeine and Taurine are applied. Caffeine is purine alkaloid, which stimulates central nervous system action, enhances the strength and frequency of the cardiac contractions and increases the excretion of urine. Taurine is a sulfur containing amino acid, which possesses many fundamental biological roles including: effect on synaptic transmission in the central nervous system, cardiotropic action, antioxidant and anticonvulsant activity, improvement of energy processes, stimulation of reparative processes in tissues, protection of eyes cataract, decrease of cholesterol and stimulation of immune system. The combination of Caffeine and Taurine provide benefit due to obtaining synergism of pharmacological effects in increasing of physical activity, stimulation of brain action, cognition, memory and attention. In connection with the significant enlarging of the consumption of energy drinks, especially by children and young people in recent years the requirements for regulation and control of the labeling of these products in many countries are enlarged. In many food additives Caffeine and Taurine are added in not labeled high concentrations, which can provoke and increase their side effects. High consumption of Caffeine enhances its adverse effects on body: anxiety, headache, insomnia, nervousness, respiratory disorders, tachycardia, tremor, dehydration. In children the adverse reactions of Caffeine in much lower doses than adults are occurred. In high concentrations Taurine has adverse effects on brain activity and can induce psoriasis. The result of combination of Caffeine and Taurine is associated with increased diuretic effect and loss of water and salts from the body, especially in children and young people. Because of these facts the quality and quantity control of included compounds in food supplements is important for their health safety.
The aim of current study was to validate spectrophotometric method with UV-detection for identification and determination of Telmisartan in 99.8 % ethanol in respect of analytical parameters: selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy and precision (repeatability). For Telmisartan in 99.8 % еthanol at λ max = 298 nm for A1%1cm and ε the obtained results for А > 0.2 and А < 0.2 are: 1) А > 0.2: at 3.10–6 g/ml ÷ 1.25.10–5 g/ml; A1%1cm: 725 ÷ 823; ε: 37347 ÷ 423352) А < 0.2: at 2.5.10–7 g/ml ÷ 1.10–6 g/ml; A1%1cm: 1201 ÷ 1567; ε: 61816 ÷ 80651 Analytical parameter accuracy is represented by the degree of recovery, which in the corresponding confidence possibility suit the confidence interval: R СТ60: 100.31 % ÷ 102.05 %; R СТ80: 99.22 % ÷ 103.18 %; R СТ100 : 93.58 % ÷ 101.9 %. For precision is proved that all results for the quantities correspond to the relevant confidence interval: СТ60: 60.31 mg ÷ 60.77 mg; СТ80: 79.82 mg ÷ 82.18 mg; СТ100: 94.22 mg ÷ 101.58 mg.
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