Nephrotoxicity of a single dose of cyclophosphamide and ifosfamide in rats

Oxazaphosphorines (cyclophosphamide ñ CP, ifosfamide ñ IF) are alkylating cytostatics used in chemotherapy of cancer and autoimmune diseases. They have numerous adverse effects, including uro- and nephrotoxic, dependent of the type of drug, time of therapy and presence of any coexistent nephrotoxic factors in a treated patient. Purpose of this study was to estimate the renal function and the level of urinary bladder dysfunction occurring in rats following administration of a single, large CP/IF dose. The experiment involved 30 rats who were administered a single intraperitoneal dose of 150 mg/kg b.w. of CP (group 1) or IF (group 2) or normal saline (group 3 ñ control), respectively. Following the administration animals were placed in individual metabolic cages. 24 h later rats were sacrificed, blood collected and nephrectomy and cystectomy performed in order to prepare specimens for histopathological analysis. Circadian diuresis was also assessed, along with a qualitative urine assessment with strip tests and laboratory renal function parameters in plasma and urine: sodium, urea, creatinine and uric acid levels, and circadian elimination of sodium, potassium, urea, creatinine, uric acid and protein. Creatinine clearance, urea clearance and fractionated sodium elimination (FENa) and renal failure index (RFI) were also calculated. An increased diuresis and acidification of urine with reduced circadian elimination of potassium and a significant proteinuria, as well as increased plasma levels of creatinine and urea were found in the group of rats that received a single dose of CP, compared to control animals. Rats treated with IF also demonstrated acidification of urine, reduced circadian potassium elimination, a significant proteinuria and increased plasma creatinine and urea levels, but their diuresis was comparable to that observed in control animals. IF-treated animals were also characterized by reduced urea clearance, FENa and RFI. Histopathological analysis confirmed presence of inflammatory changes in urinary bladders in both groups 1 and 2, and absence of any significant morphological disorders in kidneys. Obtained results suggest a dysfunction of distal tubules and collective tubules developing as a result of administration of a single nephrotoxic dose of IF/CP. FENa and RFI results indicate also a higher nephrotoxic potential of IF administered as a single dose

Matrix Metalloproteinases in Cardioembolic Stroke : From Background to Complications

Matrix metalloproteinases (MMPs) are endopeptidases participating in physiological processes of the brain, maintaining the blood–brain barrier integrity and playing a critical role in cerebral ischemia. In the acute phase of stroke activity, the expression of MMPs increase and is associated with adverse effects, but in the post-stroke phase, MMPs contribute to the process of healing by remodeling tissue lesions. The imbalance between MMPs and their inhibitors results in excessive fibrosis associated with the enhanced risk of atrial fibrillation (AF), which is the main cause of cardioembolic strokes. MMPs activity disturbances were observed in the development of hypertension, diabetes, heart failure and vascular disease enclosed in CHA2DS2VASc score, the scale commonly used to evaluate the risk of thromboembolic complications risk in AF patients. MMPs involved in hemorrhagic complications of stroke and activated by reperfusion therapy may also worsen the stroke outcome. In the present review, we briefly summarize the role of MMPs in the ischemic stroke with particular consideration of the cardioembolic stroke and its complications. Moreover, we discuss the genetic background, regulation pathways, clinical risk factors and impact of MMPs on the clinical outcome

Disorders of the Cholinergic System in COVID-19 Era—A Review of the Latest Research

The appearance of the SARS-CoV-2 virus initiated many studies on the effects of the virus on the human body. So far, its negative influence on the functioning of many morphological and physiological units, including the nervous system, has been demonstrated. Consequently, research has been conducted on the changes that SARS-CoV-2 may cause in the cholinergic system. The aim of this study is to review the latest research from the years 2020/2021 regarding disorders in the cholinergic system caused by the SARS-CoV-2 virus. As a result of the research, it was found that the presence of the COVID-19 virus disrupts the activity of the cholinergic system, for example, causing the development of myasthenia gravis or a change in acetylcholine activity. The SARS-CoV-2 spike protein has a sequence similar to neurotoxins, capable of binding nicotinic acetylcholine receptors (nAChR). This may be proof that SARS-CoV-2 can bind nAChR. Nicotine and caffeine have similar structures to antiviral drugs, capable of binding angiotensin-converting enzyme 2 (ACE 2) epitopes that are recognized by SARS-CoV-2, with the potential to inhibit the formation of the ACE 2/SARS-CoV-2 complex. The blocking is enhanced when nicotine and caffeine are used together with antiviral drugs. This is proof that nAChR agonists can be used along with antiviral drugs in COVID-19 therapy. As a result, it is possible to develop COVID-19 therapies that use these compounds to reduce cytokine production. Another promising therapy is non-invasive stimulation of the vagus nerve, which soothes the body’s cytokine storm. Research on the influence of COVID-19 on the cholinergic system is an area that should continue to be developed as there is a need for further research. It can be firmly stated that COVID-19 causes a dysregulation of the cholinergic system, which leads to a need for further research, because there are many promising therapies that will prevent the SARS-CoV-2 virus from binding to the nicotinic receptor. There is a need for further research, both in vitro and in vivo. It should be noted that in the functioning of the cholinergic system and its connection with the activity of the COVID-19 virus, there might be many promising dependencies and solutions

The Effect of α-Tocopherol on the Reduction of Inflammatory Processes and the Negative Effect of Acrylamide

Our research aimed to show acrylamide’s influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA

Reply to Cafiero et al. Comment on “Kopańska et al. Disorders of the Cholinergic System in COVID-19 Era—A Review of the Latest Research. Int. J. Mol. Sci. 2022, 23, 672”

We have carefully read the Letter to the Editor by Concetta Cafiero, Alessandra Micera, Agnese Re, Beniamino Schiavone, Giulio Benincasa, and Raffaele Palmirotta related to our paper entitled “Disorders of the Cholinergic System in COVID-19 Era—A Review of the Latest Research” [...

Acrylamide Neurotoxicity as a Possible Factor Responsible for Inflammation in the Cholinergic Nervous System

Acrylamide (ACR) is a chemical compound that exhibits neurotoxic and genotoxic effects. It causes neurological symptoms such as tremors, general weakness, numbness, tingling in the limbs or ataxia. Numerous scientific studies show the effect of ACR on nerve endings and its close connection with the cholinergic system. The cholinergic system is part of the autonomic nervous system that regulates higher cortical functions related to memory, learning, concentration and attention. Within the cholinergic system, there are cholinergic neurons, anatomical cholinergic structures, the neurotransmitter acetylcholine (ACh) and cholinergic receptors. Some scientific reports suggest a negative effect of ACR on the cholinergic system and inflammatory reactions within the body. The aim of the study was to review the current state of knowledge on the influence of acrylamide on the cholinergic system and to evaluate its possible effect on inflammatory processes. The cholinergic anti-inflammatory pathway (CAP) is a neuroimmunomodulatory pathway that is located in the blood and mucous membranes. The role of CAP is to stop the inflammatory response in the appropriate moment. It prevents the synthesis and the release of pro-inflammatory cytokines and ultimately regulates the local and systemic immune response. The cellular molecular mechanism for inhibiting cytokine synthesis is attributed to acetylcholine (ACh), the major vagal neurotransmitter, and the α7 nicotinic receptor (α7nAChR) subunit is a key receptor for the cholinergic anti-inflammatory pathway. The combination of ACh with α7nAChR results in inhibition of the synthesis and release of pro-inflammatory cytokines. The blood AChE is able to terminate the stimulation of the cholinergic anti-inflammatory pathway due to splitting ACh. Accordingly, cytokine production is essential for pathogen protection and tissue repair, but over-release of cytokines can lead to systemic inflammation, organ failure, and death. Inflammatory responses are precisely regulated to effectively protect against harmful stimuli. The central nervous system dynamically interacts with the immune system, modulating inflammation through the humoral and nervous pathways. The stress-induced rise in acetylcholine (ACh) level acts to ease the inflammatory response and restore homeostasis. This signaling process ends when ACh is hydrolyzed by acetylcholinesterase (AChE). There are many scientific reports indicating the harmful effects of ACR on AChE. Most of them indicate that ACR reduces the concentration and activity of AChE. Due to the neurotoxic effect of acrylamide, which is related to the disturbance of the secretion of neurotransmitters, and its influence on the disturbance of acetylcholinesterase activity, it can be concluded that it disturbs the normal inflammatory response

MiniQEEG and Neurofeedback in Diagnosis and Treatment of COVID-19-Related Panic Attacks: A Case Report

Background: Both the global COVID-19 pandemic situation, as well as the current political situation in Eastern Europe may exacerbate anxiety and contribute to stress-related disorders such as panic disorder. Electroencephalography (EEG)-based neurofeedback provides both assessment of the subject’s brainwave activity as well as the possibility of its therapeutic correction. It is possible that it can be implemented as an auxiliary treatment in panic disorders of different origin. The aim of this feasibility study was to demonstrate (both short- and long-term) effectiveness of neurofeedback therapy in a patient with previously diagnosed panic attacks, related to fear of COVID-19 infection. Methods: We report the case study of a 47-year-old man affected by panic attacks, related to his profound, constant fear of COVID-19 infection and its sequelae. For the initial diagnostic workup, several clinical and research tools were used: 1. Baseline psychological exam; 2. Anxiety—targeted interview performed by miniQEEG therapist; 3. Analysis of previous clinical test results (EEG record/lab blood test); and 4. The miniQEEG exam (central strip recording Cz-C3-C4), The patient was subjected to regular EEG Neurofeedback sessions for two consecutive months. After completing the treatment, follow-up tests, as listed above were repeated immediately after completing the whole treatment program, as well as 1 and 2 years later. MiniQEEG results were compared with healthy control (age-matched male subject not affected with panic attacks) and evaluated over the time that the subject was involved in the study. Results: Initially, the patient was suffering from severe panic attacks accompanied by vegetative symptoms and from destructive and negative thoughts. After 8 consecutive weeks of treatment encompassing sixteen QEEG neurofeedback training sessions (each lasting 30 min), a subjective improvement of his complaints was reported. More importantly, QEEG records of the patient also improved, approximating the pattern of QEEG recorded in the healthy control. Conclusion: In this single case-based feasibility analysis, we demonstrate that systematic application of QEEG-Neurofeedback may result in manifest and durable therapeutic effect. Of note, use of this treatment may be a valuable option for patients with panic attack/panic disorder, especially if related to the psychological burden of the COVID-19/war era. Future studies on a larger patient population, especially with a longitudinal/prospective design, are warranted

Osteopontin and fatty acid binding protein in ifosfamide-treated rats

Ifosfamide (IF) is a cytostatic that exhibits adverse nephrotoxic properties. Clinically, IF-induced nephrotoxicity takes various forms, depending on applied dose and length of treatment

Urinary incontinence in women: biofeedback as an innovative treatment method

Urinary incontinence is an involuntary urination (leakage of urine). About 200 million people suffer from this condition, and 60% of cases are concealed and untreated because of shame. It is estimated that an increasing number of young women and women of menopausal age will suffer from urinary incontinence. This disease occurs during the perinatal, perimenopausal period, as a result of brain damage or an unhealthy lifestyle. There are four main types of urinary incontinence: stress, urge, overflow and mixed form. Treatment is adapted to the severity of disease, its type and includes physiotherapeutic treatment (kinesiotherapy, physiotherapy, massage), pharmacological, psychological and surgical treatment. In recent years, growing interest has been observed in the noninvasive biofeedback method. The patient learns to contract the weakened pelvic floor muscles, constantly monitoring progress in treatment. She is also motivated by visual and auditory stimuli. Growing evidence confirms the effectiveness of this method, which to a large extent eliminates urinary incontinence. Nevertheless, attention should also be paid to prevention, which reduces the risk of involuntary leakage of urine

The Use of Neurofeedback in Sports Training: Systematic Review

Biofeedback training is a method commonly used in various fields of life, for example, in medicine, sports training or business. In recent studies, it has been shown that biofeedback, and neurofeedback, can affect the performance of professional athletes. Training based on the neurofeedback method includes exercising the brain waves. The aim of the article is to evaluate the influence of neurofeedback training on the physical fitness of professional athletes representing various sports disciplines, such as judo, volleyball and soccer. Based on 10 scientific papers from various sources, including PubMed, the latest research on neurofeedback and its impact on athletes has been reviewed. On the basis of the literature review from 2012 to 2022 on the neurofeedback method in sports training, it can be stated that this type of practice has a significant impact on physical fitness and sports performance. This review comprised 10 research studies with 491 participants in the neurofeedback groups, and 62 participants in the control group. Two reviewers independently extracted data and evaluated the quality of the studies utilising the PEDro scale. Properly planned and conducted neurofeedback training affects stimulation and improvement of many variables (reducing stress levels, increasing the ability to self-control physiological factors, enhancing behavioural efficiency and meliorating the speed of reaction to a stimulus)