EFFECT OF AMIODARONE ON RABBITS' OPTIC NERVE AND THE AMELIORATIVE EFFECT OF VITAMIN E: FTIR STUDY

Objective: The study aimed to investigate the structural and conformational changes induced by short-term administration of the amiodarone in the optic nerve besides validating whether vitamin E coadministration with amiodarone will improve these changes. Methods: Thirty New Zealand white rabbits from both sexes were haphazardly categorized into three groups, whereas each group contains ten rabbits (20 eyes). One of these groups served as a control that received an intraperitoneal injection of normal saline. Rabbits in the second group intraperitoneally (ip) injected daily with 160 mg/kg body weight (bw) of amiodarone for two weeks. The last group orally administration 100 mg/kg bw of vitamin E with the 160 mg/kg bw of amiodarone ip daily for two weeks until the time of sacrifice. Fourier transform infrared spectroscopy (FTIR) analysis was conducted on the optic nerve of the all groups. Results: The results obtained from the FTIR spectrum revealed that the short-term administration of amiodarone caused a significant alteration in the stretching NH-OH region. A newly detected component centered at 3739±1 cm-1 was assigned as strO-H. There was a significant decrease (p˂0.05) in the bandwidth and band position of one component of strO-H that centered at 3598±1 cm-1. Moreover, remaining vibrational bands (O-Hasym and O-Hsym) were shifted to higher frequencies. Coadministration of vitamin E with amiodarone reduced the contour to four components as a control with significant increase in the band position of O-Hasym and the bandwidth of one component of str O-H. Amiodarone administrations lead to reducing the area ratio of asymCH2 to symCH2 and elevation of the area ratio of asymCH2 to asymCH3 while the coadministration of vitamin E returned it as the control ratio. The percentage of the β-turn was significantly increased while the α-helix content was decreased due to amiodarone. The contents of both components were considered mimicking the control values when Vitamin E was co-administered with amiodarone. Conclusion: The study stated that amiodarone could change the solubility and folding of the optic nerve proteins. Finally, vitamin E intake with amiodarone turns many of these changes induced by amiodarone to normal levels, which make it a good supplement for amiodarone users.

Acitretin-Conjugated Dextran Nanoparticles Ameliorate Psoriasis-like Skin Disease at Low Dosages

Psoriasis is a common chronic inflammatory skin disease mainly characterized by keratinocyte hyperproliferation and massive infiltration of inflammatory immune cells. Acitretin (ACT), an FDA-approved first-line systemic drug for psoriasis treatment, could suppress the proliferation of keratinocytes and downregulate the expression of inflammatory cytokines by modulating signal transducer and activator of transcription (STAT) signaling pathways. However, dose-dependent side effects of ACT limit its long-term administration in the clinic. Therefore, improving the therapeutic efficacy of ACT to reduce clinical dosage will benefit the patients. Here, we develop ACT-conjugated dextran nanoparticles (ACT-Dex NPs) and evaluated the potential for psoriasis treatment. Our results indicate that ACT-Dex NPs ameliorate psoriasis-like skin disease significantly at a low dosage which does not cause side effects, while neat ACT drugs at an equivalent dosage provide much less benefit. Moreover, we demonstrate that ACT-Dex NPs suppress keratinocyte proliferation more efficiently than neat ACT by enhancing the inhibitory effect on STAT3 phosphorylation. Thus, the proposed ACT-Dex NPs provide an effective and safe option for psoriasis treatment.

Curcumin Supplementation (Meriva®) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease

Chronic kidney disease (CKD) subjects suffer from high risk of cardiovascular mortality, and any intervention preventing the progression of CKD may have an enormous impact on public health. In the last decade, there has been growing awareness that the gut microbiota (GM) can play a pivotal role in controlling the pathogenesis of systemic inflammatory state and CKD progression. To ameliorate the quality of life in CKD subjects, the use of dietary supplements has increased over time. Among those, curcumin has demonstrated significant in vitro anti-inflammatory properties. In this pilot study, 24 CKD patients and 20 healthy volunteers were recruited. CKD patients followed nutritional counselling and were supplemented with curcumin (Meriva®) for six months. Different parameters were evaluated at baseline and after 3–6 months: uremic toxins, metagenomic of GM, and nutritional, inflammatory, and oxidative status. Curcumin significantly reduced plasma pro-inflammatory mediators (CCL-2, IFN-γ, and IL-4) and lipid peroxidation. Regarding GM, after 6 months of curcumin supplementation, Escherichia-Shigella was significantly lower, while Lachnoclostridium was significant higher. Notably, at family level, Lactobacillaceae spp. were found significantly higher in the last 3 months of supplementation. No adverse events were observed in the supplemented group, confirming the good safety profile of curcumin phytosome after long-term administration.

Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer’s Disease Mice

Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

Effects of long-term oral administration of melatonin on tear production, intraocular pressure, and tear and serum melatonin concentrations in healthy dogs

OBJECTIVE To evaluate the effects of long-term (30-day) oral administration of melatonin on tear production, intraocular pressure (IOP), and concentration of melatonin in the tears and serum of healthy dogs. ANIMALS 20 healthy sexually intact adult male dogs. PROCEDURES 10 dogs were given melatonin (0.3 mg/kg, PO, q 24 h, administered in food at 9 am), and 10 dogs were given a placebo. Tear and serum melatonin concentrations, IOP, and tear production (determined with a Schirmer tear test) were recorded before (baseline) and 30 minutes, 3 hours, and 5 hours after administration of melatonin or the placebo on day 1 and 30 minutes after administration of melatonin or the placebo on days 8, 15, and 30. RESULTS Data collection time had significant effects on tear production, IOP, and tear melatonin concentration but not on serum melatonin concentration. Treatment (melatonin vs placebo) had a significant effect on tear melatonin concentration, but not on tear production, IOP, or serum melatonin concentration; however, tear melatonin concentration was significantly different between groups only 30 minutes after administration on day 1 and not at other times. CLINICAL RELEVANCE In healthy dogs, long-term administration of melatonin at a dosage of 0.3 mg/kg, PO, every 24 hours did not have any clinically important effects on tear production, IOP, or serum or tear melatonin concentrations.

Clinical and morphological phenotypes in intrathoracic sarcoidosis

Aim. To study clinical and morphological phenotypes in different variants of the course of intrathoracic sarcoidosis and isolate new phenotypes.Materials and methods. The study included 121 patients with intrathoracic sarcoidosis aged 21–66 years (50.4% were men, 49.6% were women, the average age at the time of the disease onset was 38 years) over the period 2007– 2019. During the examination, patients’ complaints were studied thoroughly, and the diagnosis was histologically verified in all cases. During an extended histological examination, the quantitative and qualitative composition of biopsy specimens was investigated. The number of granulomas in the field of vision and the content of giant cells, macrophages, lymphocytes, neutrophils, and eosinophils in them were studied. Qualitative parameters were assessed for the presence of hyalinosis, Schaumann bodies, necrosis, stamping, calcification, fibrosis, and vasculitis. All patients were retrospectively divided into two clinical groups depending on the outcomes of the disease: group 1 included patients with a favorable course of sarcoidosis, proceeding without relapses and signs of progression; group 2 encompassed patients with an unfavorable course of the disease with relapses and progression, requiring long-term administration of systemic glucocorticoids.Results. The analysis showed that among all general clinical manifestations, only the presence of dyspnea, skin manifestations, and weight loss occurred significantly more often in the patients with an unfavorable course of intrathoracic sarcoidosis (р = 0.04; 0.02; and 0.01, respectively). Among morphological parameters, a large number of macrophages was significantly more frequent in the biopsy specimens in this group of patients (р < 0.01).

The State of the Neuronal-Astrocytic Apparatus of the Hippocampus on the Background of Long-Term Administration of Isoniazid and Rifampicin under Conditions of Correction of the Gut Microflora

The purpose of the study was to determine the morphometric and ultrastructural features of neurons and glial cells, as well as the levels of glial fibrillar acid protein in the hippocampus of rats under long-term administration of isoniazid and rifampicin during experimental therapy with a combination of pro/prebiotics. Materials and methods. The studies were conducted on three groups of white Wistar male rats with drug-induced hepatitis, reproduced by intragastric administration of isoniazid and rifampicin for 28 days. In the last 14 days of the intragastric experiment, rats of the research group were administered probiotic and prebiotic. The content of cytosolic glial fibrillar acid protein in the hippocampus was determined by competitive enzyme-linked immunosorbent assay. Semi-thin sections of CA1 sections of the rat hippocampus were analyzed using the Image J. analysis program. The ultrastructural characteristics were studied using a PEM-100-01 transmission electron microscope (Selmi, Ukraine). Results and discussion. Long-term administration of isoniazid and rifampicin was associated with changes in the content of the cytosolic fraction of glial fibrillar acid protein obtained from the hippocampus. These changes were characterized by a tendency to increase the level of this protein by 17.8% (p=0.2) compared with intact animals. In contrast to the group of animals reproduced in the experiment drug-induced liver injury, in the experimental group, the level of glial fibrillar acid protein was significantly lower by 25.0% compared to the drug-induced liver injury group (p <0.05). Morphological analysis revealed a decrease in neuronal density in rats with drug-induced liver injury compared with intact control. At the same time, the specific number of degeneratively altered neurons in comparison with intact control in the group of drug-induced liver injury animals increased by 8.57 times. The number of degeneratively altered neurons in the group receiving yogurt / lactulose was 55.87 ± 4.23%, which was significantly higher than intact control rats, but was 19.4% (p <0.05) lower levels in rats with MIUP. Electron microscopic examination of rat hippocampal neuroglia was based on the study of changes in the astrocytic and oligodendroglial components. Changes in rat hippocampal neuroglia under experimental conditions were mainly related to the astrocytic link. Astrocytes were characterized by significantly lower cytoplasmic edema and adaptive-compensatory changes in the cell. Conclusion. Course administration of pro/prebiotics reduces the severity of manifestations of neurodegeneration, improves the state of astroglia in the hippocampus, and reduces the cytoplasmic levels of glial acidic fibrillar protein in animals with drug-induced liver injury

The Effect of Acute Oral Galactose Administration on the Redox System of the Rat Small Intestine

Galactose is a ubiquitous monosaccharide with important yet incompletely understood nutritive and physiological roles. Chronic parenteral d-galactose administration is used for modeling aging-related pathophysiological processes in rodents due to its ability to induce oxidative stress (OS). Conversely, chronic oral d-galactose administration prevents and alleviates cognitive decline in a rat model of sporadic Alzheimer’s disease, indicating that galactose may exert beneficial health effects by acting in the gut. The present aim was to explore the acute time-response of intestinal redox homeostasis following oral administration of d-galactose. Male Wistar rats were euthanized at baseline (n = 6), 30 (n = 6), 60 (n = 6), and 120 (n = 6) minutes following orogastric administration of d-galactose (200 mg/kg). The overall reductive capacity, lipid peroxidation, the concentration of low-molecular-weight thiols (LMWT) and protein sulfhydryls (SH), the activity of Mn and Cu/Zn superoxide dismutases (SOD), reduced and oxidized fractions of nicotinamide adenine dinucleotide phosphates (NADPH/NADP), and the hydrogen peroxide dissociation rate were analyzed in duodenum and ileum. Acute oral administration of d-galactose increased the activity of SODs and decreased intestinal lipid peroxidation and nucleophilic substrates (LMWT, SH, NADPH), indicating activation of peroxidative damage defense pathways. The redox system of the small intestine can acutely tolerate even high luminal concentrations of galactose (0.55 M), and oral galactose treatment is associated with a reduction rather than the increment of the intestinal OS. The ability of oral d-galactose to modulate intestinal OS should be further explored in the context of intestinal barrier maintenance, and beneficial cognitive effects associated with long-term administration of low doses of d-galactose.

Osteoporosis in rheumatic diseases

The article presents a review of studies that have examined osteoporosis in rheumatic diseases, including rheumatoid arthritis, spondylarthritis, psoriatic arthritis, systemic connective tissue diseases, and systemic vasculitis. The review discusses the pathogenesis, diagnosis and treatment of osteoporosis in these diseases, presents the results of epidemiological studies assessing the risk factors and the prevalence of osteoporosis in rheumatic diseases. There was a high prevalence of osteoporosis and fractures in rheumatic diseases, exceeding the population, associated primarily with systemic and local inflammation, as well as with the intake of glucocorticoids. It is indicated that the existing strategies for the treatment of rheumatic diseases may partially reduce bone loss, but long-term administration of glucocorticoids, on the contrary, increase bone resorption. The review presents data on the medications for the treatment of osteoporosis and approaches to the treatment of glucocorticoid osteoporosis.