Dry age-related macular degeneration - therapeutic possibilities and research directions

Age-related macular degeneration (AMD) is a major cause of vision loss in developed countries, especially in the elderly population. AMD is a multifactorial disease which etiology is not completely understood. Studies confirm the strong relationship between age and AMD, probably as a result of the complex interaction of metabolic, functional, genetic, and environmental factors that cause important changes in the macular structure (i.e., choriocapillary, Bruch’s membrane, retinal pigmented epithelium, and photoreceptors) that define the symptoms of the disease. Clinically there are two forms of AMD- dry (atrophic) and wet (neovascular). Currently, the gold standard of treatment in wet AMD is the immediate introduction of anti-VEGF (VEGF, vascular endothelial growth factor) therapy in the form of intravitreal injections. There are four preparations of anti-VEGF drugs available in Poland. The three approved for ophthalmic indications are ranibizumab (Lucentis), aflibercept (Eylea), brolucisumab (Beovu) and off-label bevacizumab (Avastin). There are no effective treatments for dry AMD. Currently, the management of dry AMD comes down to preventing the progression of an existing degeneration and - more importantly - inhibiting its transition to neovascular form. Counseling on the need to modify lifestyle by switching to the antioxidant-rich diet, stopping smoking, controlling blood pressure, body weight, using glasses with protective filters, visual rehabilitation and vitamin supplementation (according to the results of the AREDS study) may reduce the risk of the disease progression. Currently, intensive research is underway to develop effective therapeutic solutions in the dry form of AMD, they include the search for substances with antioxidant, anti-inflammatory, neuroprotective properties, complement cascade inhibitors, as well as gene therapy and cell transplantation. New treatment studies are focused on preventing the progression of degeneration and repopulating the atrophic macula. This article reviews the current options and future perspectives for the treatment of AMD, particularly its dry form

Interactions between dietary omega-3 polyunsaturated fatty acids and the gut microbiota

The gut microbiota forms a complex and metabolically active ecosystem. Changes in gut microbiota activity correlate with the health status.. It is not known whether the dysfunction of the intestinal microbiota due to undesirable changes in the qualitative and quantitative composition (so-called dysbiosis) is a cause or effect of disease states. Long-term dietary habits play a key role in the formation of the human-specific gut microbiota. Despite many publications on the effects of carbohydrates with prebiotic properties, the effects of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota are not fully explained. The main bioactive forms in humans among omega-3 PUFAs, are eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). These compounds play an important role in the proper functioning of the human body, as well as in the prevention and treatment of many diseases, so they are widely used as nutraceuticals. Few studies with adults have shown changes in gut microbiota after omega-3 PUFAs supplementation and a reduction in dysbiosis. Omega-3 PUFAs can influence the diversity and abundance of the gut microbiome, on the other hand, gut microbes can affect the metabolism and absorption of these compounds. Omega-3 PUFAs affect the gut microbiome in three main ways: by modulating the type and abundance of intestinal microbes, by altering the levels of proinflammatory mediators such as endotoxins (lipopolysaccharides) and interleukine 17; and by regulating the levels of short-chain fatty acids (SCFAs). The aim of this study was to summarize the current state of knowledge on the biological activity of the intestinal microbiota, particularly the interactions of the microbiota and omega-3 polyunsaturated fatty acids in humans. The data search was performed in July 2023 in the PubMed database and publicly available literature using the following queries: "intestinal microbiota", "microbiome", "omega-3 polyunsaturated acids intestinal microbiota", "EPA intestinal microbiota", "DHA intestinal microbiota". The article discusses the interactions between the intestinal microbiota and omega-3 PUFAs. The issues presented allow to conclude that elucidating the mechanisms of interaction between the gut microbiota and omega-3 PUFAs, may provide the basis for developing more effective therapeutic strategies

Phytic acid inhibits lipid peroxidation in vitro.

Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 M and 500 M effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10-20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100 M and 500 M significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 M and 500 M) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products

Comparative "in vitro" studies of furazidin and nitrofurantoin activities against common uropathogens including multidrug-resistant strains of "E. coli" and "S. aureus"

Urinary tract infections caused by wide range of pathogens including gram-negative andgram-positive bacteria as well as fungi are a severe public health problem. The predominant causative agent of both uncomplicated and complicated urinary tract infections is Escherichia coli. In an era of increasing bacterial resistance to antimicrobial agents and a high prevalence of multidrug-resistant (MDR) strains in communityandhospital-acquired infections, the re-evaluation of older generations of antimicrobial agents, such as nitrofuran derivatives, seems to be a reasonable approach. The aim of the study was to evaluate furazidin activity against common uropathogens in comparison to nitrofurantoin and other selected antimicrobial agents, routinely used in the treatment of urinary tract infections. Furazidin exhibited lower MICs than nitrofurantoin when tested against gram-negative and gram-positive bacteria including clinical MDR E. coli and methicillin-resistant Staphylococcus aureus. The MICs for furazidin ranged from 4 to 64 mg/L forEnterobacteriaceae strains, from 2 to 4 mg/L for gram-positive cocci, and 0.5 mg/L for anaerobic bacteria. The MICs for nitrofurantoin ranged from 16 to 64 mg/L for Enterobacteriaceae strains, from 8 to 64 mg/L for gram positive cocci, and 4 mg/L for anaerobic bacteria. In addition, both nitrofurans displayed better activity against the tested bacterial strains than ciprofloxacin, fosfomycin, trimethoprim and co-trimoxazole. Nitrofuran derivatives displayed higher antimicrobial activity than other antimicrobial agents regardless of bacteria species or resistance mechanism

Antioxidative assessment of new trans-palladium (II) complexes in head and neck cancer

Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = <0.001. Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses