Nuclear receptors (NRs) are a superfamily of transcription factors that play an important role in regulating many biological processes. The retinoid X receptor (RXR) is unique among NRs because it can form both homodimers and heterodimers with other representatives of the family. RXR modulates the expression of different genes and that is why it could be a good target for many therapies. Dysregulation of RXR signaling leads to various diseases, including neurodegenerative diseases, obesity, diabetes and cancer. Many molecules have been described as potential ligands for RXR. However, only a few of them are currently approved for clinical use. Retinoids play important role in regulation of skin cells growth and differentiation as well as have immunomodulatory and anti-inflammatory effects. Therefore they have found use in treatment of skin lesions and some types of cancers. This review summarizes general information about RXR, its structure, ligands and mechanism of action as well as its potential role in cancer therapy and metabolic syndrome.
Interferons type I (IFN-I), activated following a bacterial or viral infection, play a major role in the induction and regulation of the immune system. The immune response results in viral RNA and binds to receptors such as RIG-I-like receptors (RLRs) or Toll-like receptors, leading to the IFN-I signaling cascade. Thanks to its cellular function, IFN-I is widely used in therapies for such diseases as multiple sclerosis (MS) and hepatitis C disease (HCD).
MS is a neurological, autoimmune, chronic inflammatory disease of the central nervous system (CNS). During MS, nerve cell demyelination is observed due to the myelin heaths and oligodendrocyte damage. As a result, neuronal signal and neuron communication are attenuated. The mechanism of MS is still unknown. MS therapy applies interferon-β (IFN-β). IFN-β therapy has been used since the last century, but the therapeutic mechanism of IFN-β has not been completely understood. MS can lead to four syndromes: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS).
HCD occurs as a result of infection with the hepatitis C virus (HCV), belonging to the Flaviviridae family. HCV is a blood-borne virus with a positive single-stranded RNA. A vaccine for HCV is not available yet. HCD can lead to liver damage or cancer. In HCD interferon-α therapy (IFN-α) is applied. As with MS, the mechanism of IFN-α therapy is not completely known.
Legionella pneumophila bacteria in the natural environment parasitize the cells of selected species of protozoa and, when present in artificial water distribution systems, they become an important etiological factor of pneumonia in humans. The main determinant of the pathogenicity of these bacteria is the capability to live and multiply in pulmonary macrophages, i.e. cells specialized in phagocytosis, killing, and digesting microorganisms. A prerequisite for the development of infection is the breakdown of the killing mechanisms of macrophages and the formation of the replication vacuole LCV (Legionella-containing vacuole). The biogenesis of the LCV vacuole is possible due to the efficient functioning of the IV secretion system Dot/Icm, which is a multi-protein complex located in the inner and outer membranes of the cell envelope. The Dot/Icm system consists of 27 components, including a core-transmembrane complex, which is the structural backbone of the entire system, and a complex of coupling proteins. Genes encoding the Dot/Icm system components are organized into two regions of the bacterial chromosome. The Dot/Icm secretion system enables L. pneumophila to introduce more than 300 effector proteins into the cytosol of the host cell, whose coordinated action maintains the integrity of the replication vacuole membrane and allows the manipulation of various cell processes. An important element of the intracellular multiplication strategy of L. pneumophila is the modulation of vesicular transport, interaction with the endoplasmic reticulum, and disruption of protein biosynthesis, autophagy, and apoptosis of the host cell. Understanding the complex mechanisms of regulation and function of the Dot/Icm effector proteins is critical in the prevention and treatment of Legionnaires' disease.
Cobalamin (vitamin B12) is a water-soluble organic compound that belongs to the B group of vitamins. Because of the complex structure and polarity of vitamin Bmolecule, its proper use and transformation in the human organism require the participation of specialized proteins. The main source of cobalamin for humans is food of animal origin. Due to tissue cobalamin reserves, the symptoms of its deficiency occur after several years of insufficient food supply. However, screening for cobalamin deficiency is reasonable in people with hypocobalaminemia risk factors such as gastric or small intestinal resection, vegan diet, long-term use of metformin, histamine H2-receptor antagonists, and proton pump inhibitors, as well as old age.
Vitamin B12 as an enzyme cofactor participates in numerous intra-mitochondrial reactions and in the synthesis of methionine, which is necessary for the formation of S-adenosylmethionine, an important factor in the process of methylation of biological molecules. Through metabolic links with folic acid, cobalamin affects DNA synthesis and cell division. Currently, more and more attention is paid to the potential contribution of vitamin B12 deficiency in the pathogenesis of neurodegenerative diseases and cancers. At the molecular level, cobalamin deficiency leads to the destabilization of cellular genome, which increases the risk of malignant transformation. On the other hand, in people with cancer or at high risk of developing it, vitamin B12 may increase the expansion of neoplastic cells.
The review focuses on the research related to the function and the molecular mechanisms of transcription factor FOXN1 action. In mammals, FOXN1 is localized in the epithelium of the skin and thymus. In the skin, FOXN1 stimulates keratinocytes differentiation, regulates pigmentation process and participates in hair development and cycling. In skin wound healing processes, FOXN1 contributes to scar formation due to its involvement in reepithelialization and epithelialmesenchymal transition (EMT). Foxn1-/- mice displayed regenerative (scar-free) skin wound healing resolution, which is unique for adult mammals but characteristic for mammalian fetuses. A detailed comparative analysis of transcriptomes from the skin of adult Foxn1-/- mice and the skin of mouse fetuses (14th day of embryonic development) revealed substantial similarities in the gene expression related to tissue remodelling, cytoskeletal rearrangements, wound healing, the immune response and differentiation. The results suggest that FOXN1 is a key factor regulating the transition from scar-free (regenerative) to scar-forming (reparative) skin wound healing process during fetal development
Legionella pneumophila bacilli parasitize in the cells of phylogenetically distant hosts: protozoa in the aquatic environment and alveolar macrophages in the human body. The ability of these bacteria to multiply intracellularly in phagocytic cells specialized to destroy microorganisms is critical to the development of atypical pneumonia known as Legionnaires' disease. Located at several different loci of the bacterial chromosome, the genes of the type II secretion system of L. pneumophila encode at least 25 proteins, including enzymes with lipolytic, proteolytic, and ribonuclease activity and proteins that are unique for Legionella. In the natural environment, the T2SS system of L. pneumophila plays a decisive role in the ecology of these microorganisms, determining their ability to survive in freshwater reservoirs at low temperatures, both in planktonic form and in biofilm structures. T2SS proteins enable L. pneumophila to infect various species of protozoa, and the substrates of this system determine the extent of the protozoan host. The multiplication of bacteria in a wide range of protozoa contributes to their dissemination and transmission to anthropogenic sources. Proteins secreted by the type II secretion system also determine the ability of L. pneumophila to infect murine alveolar macrophages and bone marrow, human macrophages of the U937 and THP-1 lines, and alveolar epithelial cells. Enzymes secreted by this system, such as proteases, aminopeptidases or phospholipases, contribute to the destruction of lung tissue, in the mouse model of pneumonia. In the human body, T2SS proteins contribute to the reduction of the innate immune response to L. pneumophila infection by inhibiting the induction of pro-inflammatory cytokines (IL-6, TNF-α, IL-1, and IL-8).
The last four decades has brought significant development in the field of molecular archaeology and ancient DNA (aDNA). The novel methods cover a wide spectrum of research, ranging from the reconstruction of small fragments of mitochondrial DNA to large-scale studies of entire populations, combining sequencing of mitochondrial genomes, genes subjected to natural selection and entire nuclear genomes. Progress, particularly in the field of DNA sequencing technology, has made it possible to obtain information from paleontological and archaeological remains, thereby allowing us to examine the relationship between extinct and contemporary species. By introduction next-generation sequencing, it has become possible to recognize DNA sequence not only directly from remains but also from sediments from the depths of lakes and caves. This publication aims to provide the reader with knowledge about the possibilities and limitations of studies on human, animals and bacterial ancient DNA, as well as polish contribution to the development of this field of science.
It is well established that human body is an ecosystem for numerous microorganisms: bacteria, fungi, eukaryotic parasites, and viruses. They form a “microbiome” that under conditions of homeostasis remains in a friendly mutual relationship with the host. However, the composition and diversity of this microbe community is dynamic and can be changed under the influence of environmental factors, such as diet, antibiotic therapy, lifestyle, and the host’s genotype and immunity. The result of gut microbiome dysbiosis can lead even to cancer. The aim of this review is the description of the healthy gastrointestinal microbiome and the role of two infectious agents: Gram-negative bacteria Helicobacter pylori and Epstein-Barr virus in the development of gastric cancer in terms of gut dysbiosis. H. pylori is the most important pathogen of gastric microbiome with clear impact on its diversity. Coinfection with Epstein-Barr virus causes chronic gastritis, and the inflammatory process is significantly increased. The process of carcinogenesis begins with chronic inflammation that causes atrophic gastritis, intestinal metaplasia, dysplasia, and finally cancer. It has been proven that chronic inflammatory infection caused by infectious agents increases the risk of stomach cancer. Molecular methods that are progressively used to explore the human microbiome provide hope that this knowledge will be used for future diagnoses and therapy in the state of its dysbiosis and in cases of gastric cancer.
The pathogenesis of mental disorders and neurodegenerative diseases may be related to the composition of gut microbiota. Communication between the intestines and the brain is possible through the gut-brain axis and takes place via endocrine, neuronal and immunological mechanisms.
Presented here is a summary of the current state of knowledge on the relationship between the composition of the gut microbiota and the occurrence of mental disorders and neurodegenerative diseases.
The composition of human gut microbiota during its life is subject to fluctuations. Gut bacteria perform many functions that are beneficial to the health of the host. Under the influence of environmental factors, gut dysbiosis may occur – a state of qualitative and quantitative disturbance of gut bacterial biota.
There are clear differences between the composition of the gut microbiota of people diagnosed with mental disorders and the composition of the gut microbiota of healthy people. In such conditions as depression, schizophrenia or autism, intestinal dysbiosis is observed, which compromises the integrity of the intestinal barrier, followed by the displacement of microorganisms and their products into the general circulation. In people diagnosed with neurodegenerative diseases (Alzheimer's disease, Parkinson's disease) the composition of gut bacterial biota is different compared to healthy people. Selected types of bacteria, via the gut-brain axis, can affect brain processes.
There are relationships between the composition of the gut microbiota and the occurrence of mental disorders and neurodegenerative diseases in humans. Usually, they are associated with intestinal dysbiosis and leaky gut syndrome.
Cardiovascular disease is the most common cause of death in developed countries. Important factors leading to ischemic heart disease and strokes are hypertension and high levels of homocysteine in blood serum. The coexistence of these two factors significantly increases the risk of these diseases and premature deaths. Many studies indicate that patients with hypertension are significantly more likely to demonstrate increased blood serum homocysteine levels than those with normal blood pressure. This may be caused by a higher incidence of overweight, high intake of salt and increased uric acid levels. It has been shown that both these factors increase the prevalence of hypertension and lead to higher homocysteine levels. However, the results of some studies indicate that arterial hypertension and homocysteinemia are causally related. It was shown, among other things, that high homocysteine levels damage the endothelium and reduce nitric oxide synthesis, which may directly lead to hypertension. Serum homocysteine levels are slightly higher in patients with white coat hypertension than they are in healthy individuals and may therefore also increase the risk of cardiovascular diseases. Several authors have also shown that the levels of homocysteine in blood serum are higher in so-called non-dippers, i.e., patients with no night-time pressure drop. The lack of a 10%–20% decrease in blood pressure at night is associated with increased cardiovascular complications. Strokes occur especially frequently in older people with arterial hypertension and hyperhomocysteinemia. The administration of B vitamins and folic acid significantly reduces serum homocysteine levels. The administration of this acid also slightly, but statistically significantly, increases the effectiveness of hypotensive drugs. Large meta-analyses meta-analysis indicate that the increased supply of folic acid in patients with hypertension significantly reduces the risk of stroke. Such management is particularly effective in patients with hypertension and hyperhomocysteinemia.
Psoriasis is one of the most common chronic, incurable inflammatory skin diseases, affecting 2–4% of the general population. Etiopathogenesis of this disease remains unclear. It is widely considered to be a multifactorial disorder caused by the interaction between inherited susceptibility alleles and environmental risk factors, such as lifestyle, diet, stimulants, foci of inflammation, and psychological factors. The widespread prevalence of psoriasis is a very significant health and socioeconomic problem. Treatment of psoriasis is based on relieving the acute symptoms of the disease. Despite the implementation of many therapeutic options, including biological treatment, effectiveness of these options is not always sufficient, or in some patients it is not satisfactory. In order to properly control the symptoms of the disease, the patient should be told that the therapeutic effect is achieved not only by pharmacotherapy but also by introducing appropriate healthy habits in everyday life. This article discusses the importance of patient-controlled factors that affect the severity of psoriasis. Theimportance of regular exercise, smoking avoidance, and reduced alcohol consumption is explained, as well as the importance for psoriasis treatment of psychotherapy and spa therapy. Understanding the essence of these factors in the treatment of psoriasis is important in achieving satisfactory therapeutic effects.
The dietary supplements market is developing very dynamically, which is related to the dissemination of this category of products in the mass media, the relatively hassle-free procedure of introducing them to the Polish market and their universal availability (they can be purchased at pharmacies, herbal shops, groceries and on the Internet). By definition, supplements are intended to supplement the diet, belong to food category and have no therapeutic effect. They may be visually identical to the pharmaceutical form of medicinal products, which may mislead consumers, as long as people are unaware of how to distinguish these two groups. In addition, no requirements have been set for technological parameters or physical properties of final products in Polish legislation. The safety of dietary supplements application includes quality, the actual content of the declared ingredients and possible contamination and presence of prohibited additives. Selective control and lack of specific guidelines regarding the form of supplements leave considerable options to the producer. It may lead to products of questionable quality and completely devoid of health-promoting effects being introduced to the market, thus posing a threat to the consumer. Due to the growing consumer interest in this group of products, the legal situation of dietary supplements on the Polish market is presented with reference to European and American legislation. The procedure and basic guidelines for placing this group of products on the market, indications for use and aspects related to safety and risks associated with dietary supplements were also discussed.
Gastrointestinal cancers are one of the most common causes of cancers and cancer-related mortality worldwide. Potential biomarkers that could serve as predictive and prognostic factors in these cancers are still being sought. Adamalysines are mentioned among the proteins that could play such a role. Numerous proteins from this family are involved in the many stages of tumor formation: from the process of individual cell differentiation, through tumor growth and progression, to the formation of distant metastases. This process occurs, among others, through signaling pathways associated with the activation of insulin-like growth factors, epidermal growth factors or the effect on tumor necrosis factor TNF-α. The signal pathway associated with the activation of proinflammatory cytokines seems to be particularly important in explaining the pathomechanism of gastrointestinal adenocarcinomas. Chronic inflammation is a well-documented risk factor for the development of this group of cancer diseases.
Understanding the role of adamalysines protein family in the development and pathogenesis of gastrointestinal malignancies still requires further research. The article attempts to synthesize current knowledge on the use of selected proteins from the adamalysin family as biomarkers for gastrointestinal cancers.
Many observations indicate the existence of a relationship between reduced selenium status in the body and various thyroid diseases, including autoimmune thyroiditis. In most studies devoted to this issue, change in concentration of anti-TPO antibodies was the main measure of the effectiveness of selenium supplementation in patients with autoimmune thyroiditis. The concentration of anti-TPO has an impact on the intensity of lymphocytic infiltration in the thyroid gland and the degree of damage to this gland; therefore, reducing their concentration as a result of increased selenium consumption may contribute to more effective treatment of autoimmune thyroiditis. In some works, the evaluation of immunoregulatory effect of selenium in the course of autoimmune thyroiditis was considered in relation to a wider range of biochemical and immunological parameters (mainly changes in the production of cytokines and chemokines). Many authors have confirmed the effect of selenium on reducing the concentration of anti-TPO, but pooled results of all the studies are ambiguous. The discrepancy may have been caused by a different degree of saturation of the thyroid with selenium and iodine in patients, a different severity of the disease, different doses of selenium administered to patients, the use or non-use of simultaneous therapy with L-thyroxine, and single nucleotide polymorphisms (SNPs) occurring in genes encoding particular selenoproteins.
Based on literature, it can be concluded that the issue concerning the role of selenium in autoimmune thyroiditis is still poorly understood. There is a need to continue research evaluating the effect of selenium on the course of this disease, which should include also other parameters apart from anti-TPO. The results of such extensive research may be helpful in formulating new guidelines for supporting treatment by appropriate modification of diet, including selenium supplementation.
The incidence and prevalence of diseases caused by non-tuberculous mycobacteria (NTM) have been steadily increasing worldwide. NTM are environmental saprophytic organisms; however, a few strains are known to produce diseases in humans affecting pulmonary and extra-pulmonary sites. Although the environment is a major source of NTM infection, recent studies have shown that person-to-person dissemination could be an important transmission route for these microorganisms. Structural and functional lung defects and immunodeficiency are major risk factors for acquiring NTM infections. Diagnosis of NTM diseases is very complex owing to the necessity of distinguishing between a true pathogen and an environmental contaminant. Identification at the species level is critical due to differences in the antibiotic susceptibility patterns of various NTM strains. Such identification is mainly achieved by molecular methods; additionally, mass spectrometry (e.g., MALDI-TOF) is useful for NTM species determination. Natural resistance of NTM species to a wide spectrum of antibiotics makes prescribing treatment for NTM diseases very difficult. NTM therapy usually takes more than one year and requires multi-drug regimens, yet the outcome often remains poor. Therefore, alternatives to antibiotic therapy treatment methods is an area under active exploration. NTM infections are an active global health problem imposing the necessity for better diagnostic tools and more effective treatment methods.
Extracellular signaling molecules, among them the fibroblast growth factors (FGFs), enable cells to communicate with neighboring cells. Such signaling molecules that receive and transmit a signal require specific tyrosine kinase receptors located at the cell surface (fibroblast growth factor receptors, FGFRs). The binding of a signaling molecule to its specific receptor results in receptor dimerization and conformational changes in the cytoplasmic part of the receptor. The conformational changes lead to trans-autophosphorylation of the tyrosine kinase domains of the receptors and subsequently to induction of several downstream signaling pathways and expression of appropriate genes. The signaling pathways activated by FGFs control and coordinate cell behaviors such as cell division, migration, differentiation, and cell death. FGFs and their transmembrane receptors are widely distributed in different tissues and participate in fundamental processes during embryonic, fetal, and adult human life. The human FGF/FGFR family comprises 22 ligands and 4 high affinity receptors. In addition, FGFs bind to low affinity receptors, heparan sulfate proteoglycans at the cell surface. The availability of appropriate ligand/receptor pair, combined with the co-receptor, initiates signaling. Inappropriate FGF/FGFR signaling can cause skeletal disorders, primarily dwarfism, craniofacial malformation syndromes, mood disorders, metabolic disorders, and Kallman syndrome. In addition, aberrations in FGF/FGFR signaling have already been reported in several types of malignant diseases. Knowledge about the molecular mechanisms of FGF/FGFR activation and signaling is necessary to understand the basis of these diseases.
Recently, there has been observed a growing interest in the relationship between humans and their microbiota. Microorganisms are present on and inside of the human body, where their number can exceed the average human body cell count. Advanced research techniques allow us to better understand the molecular mechanisms of these interactions. This knowledge gives us the opportunity to use especially these microorganisms that have a positive impact on the human body in therapies and disease prevention. The article summarizes current knowledge about the physiology of the human gut bacterium Akkermansia muciniphila and its interactions with the host. The properties of A. muciniphila, its functions in the gastrointestinal tract and the relationship (both antagonistic and symbiotic) with other microorganisms residing are also described. Moreover, the effect of A. muciniphila on gut barrier, immune system and energy metabolism are presented. In addition, the role of A. muciniphila in pathogenesis and therapy of diseases such as type 2 diabetes, inflammatory bowel disease, neurological disorders and asthma is mentioned, as well as in the patient’s response to anticancer therapy based on the activation of the immune system. The great interest in A. muciniphila, as well as results of many studies presented in this article, including those evaluating its safety, indicate that A. muciniphila might be a promising candidate for a next generation probiotic. However, more studies are undoubtedly needed to assess the safety of A. muciniphila before its approving as a probiotic supplement.
In the last years, bioactive and biostatic activities of fibrin and the ability to entrapping and binding growth factors play a significant role in tissue engineering. Fibrin is most commonly applied in forms of gels and discs. Finally, every form of fibrin becomes gel as a result of water uptake. In vivo fibrin acts as a cell scaffold and can be applied as the gel in hardly accessible areas, filling damaged tissues and supporting surrounding tissues. Moreover, fibrin stops bleeding, initiates tissue repair processes, and plays the role of a cell stimulator agent. The modification of fibrin structure with adhesive molecules accelerates the reconstruction of the normal tissue. Structural properties of fibrin also make it possible to use it as a reservoir of growth factors and a controlled growth factor release system. The biodegradability of fibrin also allows for correlation of the matrices degradation with tissue reconstruction. Fibrin processing by 3D printing and electrospinning methods makes it possible to produce tailored to the injury pieces and nonwovens without losing fibrin bioactive properties. These methods could be used for the improvement of the mechanical properties of fibrin by the formulation of nonwovens with other polymers. These durable materials are especially important for the proper healing of such structures as bone and tendons. In the future, the biotechnological methods of fibrinogen synthesis may make it independent from blood source and increase the popularity of fibrin-based medical devices.
The intestinal microbiota is an integral part of the body that enables its proper functioning. Owing to intestinal microorganisms it is possible to stimulate the immune system, synthesize vitamins and improve the absorption of nutrients. However, its activity may also have adverse effects on the body, resulting e.g. from the processing of the intestinal contents. The microbiota-drug interaction described in this article is based on the positive and negative effects of intestinal microorganisms on pharmacotherapy by directly and indirectly influencing the fate of the drug in the body. Due to the fact that the microbiome is an inseparable element of the body, interfering with even a small part of it can lead to farreaching, sometimes unexpected effects. Hence, in order to improve the efficacy and safety of pharmacotherapy, it is necessary to explain the mechanisms of microbiota's influence on the fate of the drug in the body.
The article summarizes the current knowledge on the biological activity of the intestinal microbiota, in particular on the interactions of microbiota and drugs that determine the effectiveness and safety of pharmacotherapy. A search was performed in September 2020 in the databases Pubmed, Scopus, Web of Science, Cochrane Library, and gray literature using the terms: “gut microbiota”, “microbiome”, “drug metabolism”, “gut microbiota-drug interactions”. The article discusses the interactions between the microbiota and drugs, including the group of antibiotics, proton pump inhibitors, sulfonamides, 5-aminosalicylic acid derivatives, non-steroidal anti-inflammatory drugs, anti-cancer drugs, statins or metformin.
Human papillomaviruses (HPV) are the most common causative agents of harmless human infections, but persistent infection with some types of HPV poses a serious health risk, because they are associated with many cancers, including cervical cancer and an increasing number of head and neck cancers. The replication cycle of HPV is closely dependent on the differentiation of the stratified mucosal epithelium, meaning that the viral genome must be replicated by different mechanisms at different stages of cell differentiation. The establishment of infection and the maintenance of the viral genome occur in proliferating epithelial cells, where the availability of replication factors is optimal for the virus. However, the productive phase of the viral life cycle, including productive replication, late gene expression and virion production, occurs as a result of epithelial differentiation in cells that normally exit the cell cycle. The virus uses a variety of cell signalling pathways, including DNA Damage Response (DDR), to perform productive replication of its own genome. Understanding the mechanisms involved in replication cycle of HPV is needed to establish an appropriate therapeutic approach to combat HPV related diseases.
Insulin resistance is a state of decreased sensitivity of target tissues to the action of insulin, despite its normal or increased concentration in blood serum. It is a significant factor in the pathogenesis of the metabolic syndrome, including pre-diabetes and type 2 diabetes, as well as cardiovascular diseases and polycystic ovary syndrome. Nowadays, interest in the use of plant-based agents in the treatment of metabolic diseases is constantly increasing. One of these agents are plants from the barberry family containing isoquinoline alkaloids such as berberine. Current scientific evidence suggests that berberine may have a positive effect on the reduction of insulin resistance, carbohydrate metabolism and lipid metabolism. Scientists have shown that this plant alkaloid could suppress adipocyte differentiation and promote weight reduction. Other effects of berberine include a hypotensive effect and a protective on the vascular endothelium. This review largely focuses on presenting the potential use of berberine in the prevention of insulin resistance and treatment of type 2 diabetes.
Chronic, diabetic complications are the major causes of disability, reduced quality of life and premature deaths of diabetic patients. Despite significant progress in the field of pharmacotherapy, their treatment remains a considerable challenge for health care providers. The lack of causal therapy results from an insufficient understanding of the mechanisms that lead to organ damage in diabetes. It is believed that etiopathogenesis of diabetic complication is multifactorial and complex and depends on the interplay between genetic and environmental factors. In addition to the hyperglycemia-associated alterations, enhanced oxidative stress, endothelial dysfunction, induction of inflammation, recent evidence has pointed out that immunopathogenic mechanisms also play an important role in the development of these complications.
The results from experimental investigations on animals as well as on tissue cultures and clinical observations have demonstrated the involvement of the immune system in the pathogenesis of diabetic complications, which consists in the activity of autoreactive lymphocytes and the cytotoxic effect of autoantibodies. Interestingly, this has been observed not only for type 1 but also for type 2 models of diabetes. Therefore, it seems that the imbalance in the immune system resulting in self-aggression may be an important factor contributing to the dysfunction of individual organs for both types of diabetes.
A more thorough understanding of the immunopathogenesis of these disorders may change the current approach for the treatment of diabetic complications and allow the use of effective, causal therapy targeting the immune mechanisms. Identification of specific autoantibodies could improve the early diagnosis and prevention of diabetic complications. The article presents an analysis of risk factors for the most common autoimmune diseases, their relationship with type 1 and 2 diabetes, and summarizes the potential role of autoimmunity in the development of its complications based on the results of previous experimental and clinical studies.
Glutathione (γ-glutamylcysteinylglycine, GSH) is the most abundant thiol antioxidant produced in the cytosol of all mammalian cells and plays a crucial role in protecting against oxidative stress. Glutathione is synthesized de novo by the sequential action of two enzymes: γ-glutamylcysteine ligase (GCL) and glutathione synthetase (GS). GCL catalyses the first step in GSH biosynthesis, which product is γ-glutamylcysteine (γ-GC). GCL is a heterodimeric enzyme composed of catalytic (GCLc) and modulatory (GCLm) subunits encoded by two separate genes. GCL subunits are comprehensively regulated at both pre- and post-translational levels. The changes in the expression and activity of GCL can cause an imbalance in GSH levels and dysregulation of redox homeostasis. The etiology of many chronic oxidative stress-related diseases involves an impairment in the catalytic activity of GCL and decreased GSH. Preclinical studies suggest that exogenous γ-GC is able to elevate the intracellular level of GSH by providing the limiting substrate and may have potential as an adjunct treatment for diseases associated with GSH depletion.
Cognitive functions of the brain depend largely on the condition of the cell membranes and the proportion of fatty acids. It is known and accepted that arachidonic acid (AA) is one of the main ω-6 fatty acids (phospholipids) in brain cells. Metabolism of that fatty acid depends on the functionality and presence of cyclooxygenase (COX). COX is a primary enzyme in the cycle of transformation of AA to prostanoids, which may mediate response of immune cells, contributing to brain function and cognition. Two COX isoforms (COX-1 and COX-2), as well as a splice variant (COX-3), have been detected in the brain. Findings released in the last decade showed that COX-2 may play an important role in cognition. There are many preclinical and clinical reports showing its engagement in Alzheimer disease, spatial learning, and plasticity. This manuscript focuses on summarizing the above-mentioned discoveries.
Recently, the incidence rate of head and neck cancer (HNC) has been increasing significantly. It is estimated that there are over 550,000 new cases per year, of which over 130,000 are laryngeal cancers. It is assumed that in more than 60% of patients the disease is diagnosed late, at stages III–IV, which is associated with unfavorable prognoses: the average survival ranges from 15% to 45%. The mainstay of successful tumor therapy is the early detection of neoplastic tissue. The laryngological examination with the use of traditional instruments should be expanded with an endoscopic examination of the larynx using optics in the outpatient clinics. This procedure is sufficient to select patients who need a direct laryngoscopy with a surgical biopsy, usually under general anesthesia in operating room conditions. However, it may bear potential complications. In 1941, Papanicolaou and Traut showed that brush cytology could be useful in detecting precancerous conditions and cervical cancers. For decades, research on the usefulness of brush cytology in diagnosing precancerous conditions and laryngeal cancers has been conducted. This paper aims to enable the reader to understand the issues related to laryngeal cancer and present the results of the previous use of brush cytology in the diagnostic process.
Light energy is used in the therapy of various etiology diseases since ancient times. The main element determining the success of the therapy is the selection of the appropriate radiation length (NB-UVB, BB-UVB and UVA1 therapy) or the interaction between the photosensitive substance accumulated in the diseased tissue and the radiation used (PUVA therapy and photodynamic therapy). Therapeutic methods using light energy are classified based on the radiation range used. Currently, UV phototherapy is distinguished, using UVA or UVB radiation, and photodynamic therapy (PDT), which uses radiation oscillating in the range of 350-700 nm.
Due to its immunosuppressive and antiproliferative effects, UV phototherapy is used to treat dermatological diseases such as psoriasis, vitiligo and atopic dermatitis. PUVA therapy uses the synergistic effect of ultraviolet radiation (UVA) and compounds with photosensitizing action (8-methoxypsolaren, 5-methoxypsolaren). In addition, monotherapy with ultraviolet radiation A1 (UVA1), broad-band UVB (BB-UVB) and narrow-band UVB (NB-UVB) are used.
Photodynamic therapy, apart from conventional treatment methods, is a modern and non-invasive alternative used both in the diagnosis and treatment of diseases of various etiologies. In 90% of cases, PDT is used to treat dermatological diseases such as acne vulgaris or psoriasis, allowing us to avoid invasive surgical intervention. Selective cytotoxic activity towards malignant tumor cells means that photodynamic therapy is also successfully used in the oncological treatment. The great progress made in the development of innovative photosensitive substances as well as new radiation sources expands the range of applicability of photodynamic therapy.
The aim of the study is to present the current forms of phototherapy by describing the mechanism of their action, application and the possibility of adverse effects.
Macrophages are effector immune cells that have an ability to undergo polarization, i.e. a change in phenotype and their activity. Therefore, two major types of macrophages have been distinguished: classically polarized (M1) macrophages, which play a role in host defense and which have proinflammatory activity and alternatively polarized (M2) macrophages, which have a regulatory role and promote tissue regeneration. Macrophages can be found in almost all tissues of the body and thus polarization influences various processes. In the central nervous system, tissue macrophages (microglia) can be found; however, in many pathological situations macrophages can also be recruited from blood-circulating monocytes. Neurodegenerative diseases, injuries and especially autoimmune diseases are often associated with the immune system response. This response can exert significant effects on the course of the disease and/or tissue regeneration. The topic of macrophage polarization is interesting because activity of M1 and M2 cells differently affect neuronal and oligodendrocyte survival, axon growth, demyelination and remyelination processes and the blood–brain barrier permeability. This is due to differences in the production of reactive oxygen species and nitric oxide, cytokine and growth factor secretion, direct cell-to-cell communication and abilities to phagocyte. In this paper the topic was discussed in the context of stroke, spinal cord injury, Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis. In many of these pathologies, a certain temporal or spatial gradient of microglia/macrophage phenotypes is observed. Therefore, it is likely that changes of macrophage polarization can potentially promote tissue regeneration and hinder neurodegenerative diseases.
Vitamin D is extremely important for the proper functioning of the body. The most commonly known role of vitamin D is its participation in regulation of calcium-phosphate metabolism and bone mineralization. This role is crucial in the prevention of rickets in children and osteoporosis in the elderly. In recent years, numerous studies have confirmed the pleiotropic effects of vitamin D. Proper vitamin D levels in blood have a positive effect on overall health, thus reducing the risk of many diseases. Vitamin D plays, inter alia, a positive role in some diseases of the gastrointestinal tract (inflammatory bowel disease), nervous system (Parkinson disease, Alzheimer disease), and cardiovascular disease (atherosclerosis). Additionally, its positive protective effect in the case of neoplastic and immunological diseases has been noted. Some studies also confirm the relationship of vitamin D deficiency to obesity and depression. In the event of these diseases, it is possible to prevent disease and support the process of treatment by maintaining appropriate levels of 25(OH)D in the blood. Besides, sufficient blood vitamin D levels reduces the risk of developing respiratory tract infections and suppresses cytokine storm, which is responsible for most COVID-19 deaths.
The aim of the study was to present the current state of knowledge regarding the role of vitamin D in the human body, especially in the context of the impact of its abnormal level on the development of various diseases.
Alcohol use disorder (AUD) is a severe and globally widespread neurological and psychiatric problem. The treatment with currently used drugs often does not bring the expected effect. New optimization methods or directions in pharmacotherapy are still being sought. The group of bioactive ligands, targeted at neuropeptides called orexins (OXs) and their receptors (OXRs), affects a number of functions including ingestion, sleep-wake regulation, as well as the brain reward system which is the basis of addiction.
The purpose of this paper is to systematize the knowledge in the field of preclinical behavioral studies on rodents (rats and mice) in several models of alcohol consumption using the OXRs antagonists.
The results of the experiments indicated a potential efficacy of particular OXRs antagonists in the AUD treatment, especially those selectively blocking the OX1R. Among them, SB-334867 in the lowest effective dose of 3 mg/kg i.p. was most studied, as shown in the model of two-bottle choice using C57BL/6 mice. Moreover, this compound did not affect the reduction of cognitive functions. GSK1059865 was also involved in the selective reduction of ethanol intake, and simultaneously did not alter the consumption of sugar solution. The other group of selective OX2R antagonists, such as TCS-OX2-29 and LSN2424100, was less efficient.
In summary, the OX1R antagonists proved to have the potential in AUD therapy, not only through the reduction of ethanol consumption but also in the treatment of coexisting behavioral and physiological disorders, such as insomnia and anxiety.
Staphylococcus Intermedius Group (SIG) staphylococci, especially Staphylococcus pseudintermedius (S. pseudintermedius), share many features with the common human Staphylococcus aureus. The similarities concern both the phenotypic characteristics and virulence of the bacteria. It is a cause of difficulties in identifying the species of isolated staphylococci. Until now, S. pseudintermedius was considered a typically animal species, of marginal importance for humans. However, it is likely that the incidence of this staphylococcus in humans is underestimated due to the misidentification of S. pseudintermedius strains as S. aureus. The cases of infections caused by S. pseudintermedius both in humans and animals described so far in the literature show that these bacteria have a similar pathogenic potential. S. pseudintermedius also produces virulence factors that favor colonization of various body regions and infections, and may affect the species composition of the natural microbiota and the host’s immune response mechanisms. Also, S. pseudintermedius may show the ability to grow in the form of a biofilm, which significantly impedes effective antibiotic therapy in clinical practice. Due to its zoonotic potential, S. pseudintermedius deserves the attention of physicians and animal owners.
Vitamin C (L-ascorbic acid) works as a strong reductant, radical scavenger, and protector of cell membranes against primary peroxidative damage in tissues and in the extracellular fluid. L-ascorbic acid is involved in the synthesis of collagen and many other biologically relevant substances, enzyme activity, xenobiotic detoxification, and prevention of forming carcinogenic nitrosamines. It also plays a role in the immune system. Numerous data indicate that cancer patients suffer from vitamin C deficiency. Studies show that people with a low vitamin C intake have an increased risk of head and neck cancers as well as lung, gastric, pancreatic, cervical, rectal, or breast cancer. On the other hand, there is no clinical evidence to support the thesis that antioxidant supplements (including vitamin C) prevent cancer. Observational trials investigating high doses of intravenous L-ascorbic acid in previously treated cancer patients have shown that it allows an increase in quality of life and may improve physical, mental, and emotional functions, as well as reducing adverse effects of standard anticancer treatment, including fatigue, nausea, vomiting, and appetite loss. So far, there were a few randomized controlled trials and they have not reported any statistically significant improvements in the overall or progression-free survival with vitamin C, as compared to the control arm. However, preclinical data indicating a role of L-ascorbic acid in modulation of immune response and its involvement in epigenome remodeling suggest its new potential clinical applications in cancer patients, especially in combination with immunotherapy. It seems reasonable to further investigate the value of vitamin C as a supportive treatment or in combination with anticancer targeted therapy.
Pubblicato online: 14 Mar 2022 Pagine: 1038 - 1045
Astratto
Abstract
The emergence of the novel SARS-CoV-2 coronavirus and rapid spread of the COVID-19 disease it causes in late 2019 and early 2020 has since led to a global pandemic announced by the World Health Organization (WHO). The pandemic is a steadily growing social, economic, psychological, and health burden. The infection rates worldwide are climbing. COVID-19 is considered a systemic disease, potentially resulting in acute respiratory distress and cardiovascular failure leading to death. Yet, SARS-CoV-2, a novel and still under-studied virus, has been documented to cause a large variety of symptoms, in many cases including cutaneous manifestations.
This paper is a review of medical literature available to date regarding the cutaneous manifestations in the course of SARS-CoV-2 infection. It is also aimed at discussing the significance of dermatological findings for improved diagnosis and treatment of COVID-19 patients. Considering the gravity of the novel coronavirus pandemic, an improved dermatological approach would aid timely diagnosis and effective management of COVID-19, and would facilitate classification of the cutaneous abnormalities observed.
Helicobacter cinaedi (H. cinaedi) is a Gram-negative curved motile rod that causes bloodstream or enteric infections. It was suggested that H. cinaedi was involved in the progression of atherosclerosis. We aimed to investigate the presence of H. cinaedi DNA using a nested-polymerase chain reaction (PCR) in atheroma plaques from patients with atherosclerosis-induced vascular diseases. A total of 129 patients diagnosed with valvular heart disease due to atherosclerosis and 146 patients with non-atherosclerotic post-stenotic dilatation were included as the patient and the control groups, respectively. The ATCC BA847 H. cinaedi strain was used as the positive control for the nested-PCR method. We investigated H. cinaedi DNA in our study groups using the nested-PCR method and detected only six H. cinaedi DNA (4.65%) in the 129 atherosclerotic patient group. We detected significant difference between patient and control groups with respect to the presence of H. cinaedi on the basis of Fischer’s exact test (p = 0.010) by univariate analysis. Age (OR: 1.042, p = 0.016), total cholesterol (≥200 mg/dL) (OR: 1.849, p = 0.0001), and high-density lipoprotein (≥50 mg/dL) (OR: 0.745, p = 0.039) levels were detected as independent variables for the risk of atherosclerosis development in the patient group. The presence of H. cinaedi was not detected as an independent variable in a multivariate analysis. Previous studies suggested that H. cinaedi-induced oral infections might translocate to vascular tissue and induce chronic inflammation in the aorta, which subsequently may lead to atherosclerotic plaque formation. In conclusion, we could not suggest that there is a causal relationship between H. cinaedi and the development of atherosclerosis. However, age (OR: 1.042), total cholesterol (≥200 mg/dL, OR: 1.849), and high-density lipoprotein (≥50 mg/dL, OR: 0.745, as protective) levels have a significant role in the pathogenesis of atherosclerosis development. We also suggest that the presence of H. cinaedi may contribute to the risk of atherosclerosis development due to the univariate comparison result.
Introduction. Stomatitis (oral mucositis) is a very serious adverse effect of anticancer therapy, and it may exacerbate treatment outcomes as well as prognoses. Stomatitis is associated with pain during chewing and swallowing, causing discomfort and interfering with eating. It can also lead to weight loss and a delay in child growth and development. None of the numerous therapies used for stomatitis management can be considered universal or sufficiently effective. Allogeneic platelet gel, a formulation that adheres closely to mucosal lesions and is rich in growth factors, may be an effective treatment for accelerating the erosion-healing process. Methods. A prospective, open-label study on the efficacy of platelet gel used for the treatment of stomatitis in children during chemotherapy. Platelet gel was applied to oral mucosal lesions four times a day. Results. 28 patients with Grade II and Grade III stomatitis were enrolled in the study. The first day after applying platelet gel, 93% of patients reported relief from pain. Within 4 to 5 days, one degree of mucosal lesion regression was reported in 89% of patients, indicating a 3 to 5 day reduction in therapy compared to our previous experience. In only two patients did we observe mild adverse events in the form of a burning sensation. Conclusion. Platelet gel contributed to both pain reduction and acceleration of the oral mucosa healing process. It is a safe and effective therapy for children with stomatitis induced by chemotherapy.
The study aimed to evaluate if costal cartilage is a good source of DNA for genetic individual identification tests performed in forensic autopsies.
Materials and Methods
The study included samples of costal cartilage collected from 80 cadavers retrieved from different environments: indoors (flat/hospital), outdoors (primarily in the forest), a coal mine, a fire site, uninhabited buildings, a basement, bodies of fresh water, exhumation sites, and unknown locations. After isolation of DNA chondrocytes, T. Large autosomal chromosome (214 bp), T. Small autosomal chromosome (80 bp), and the Y chromosome (75 bp; for male cadavers), sequences were amplified using real-time PCR. Additionally, 23 autosomal short tandem repeat (STR) loci and 16 Y chromosome STR loci were amplified using multiplex PCR. Forensic DNA typing was done using capillary electrophoresis and all results were analyzed.
Results
There was no statistically significant difference in DNA concentration after T. Large, T. Small autosomal chromosome and the Y chromosome amplification between samples collected from cadavers retrieved from different environments. The DNA degradation index was the same regardless of the postmortem interval. The results show that it is possible to generate a full genetic profile from costal cartilage samples collected from cadavers retrieved from different environments and at different times elapsed after death.
Conclusions
The results suggest that costal cartilage can be routinely collected during forensic autopsies, especially from cadavers at the advanced decomposition stage.
Paraoxonase 1 is an enzyme associated with high-density lipoprotein fraction and is considered to present antioxidant activity.
Objectives
The aim of the study was to assess the arylesterase activity of paraoxonase 1 (PON1) in the serum of patients with hypertension, due to effect of therapy and before treatment. Patients and Methods. The study was conducted in 76 patients with primary hypertension and 28 volunteers for the control group. Hypertensive subjects were assigned to one of three groups: well controlled (n=25), poorly controlled (n=26), and newly diagnosed before therapy (n=25) hypertension. We evaluated metabolic parameters in all participants using routine laboratory methods, as well as arylesterase activity of PON1.
Results
The four study groups differed with arylesterase activity of PON1 and the highest levels were found in patients with well controlled hypertension and the lowest in newly diagnosed. All patients diagnosed with hypertension presented negative correlations between PON1 and systolic and diastolic blood pressure.
Conclusions
Effective treatment of hypertension could result in increased PON1 activity, despite unfavorable homocysteine concentrations in blood. Untreated hypertension might decrease activity of PON.
The article presents the results of an in vitro study aimed at identifying changes in parameters of oxidative stress – concentration of malondialdehyde (MDA), enzymatic activity of superoxide dismutase (SOD-1) and protective antioxidant role of melatonin (MLT) during the exposure of blood platelets to electromagnetic radiation (EMR) emitted by monitors.
Methods
Platelets were exposed to an EMR for 30- and 60 min. generated by monitors (1 kHz frequency, 220 V/m intensity). In each sample the level of SOD-1 activity and concentration of MDA were determined.
Results
The MDA concentration increased significantly after 30-and 60-min. irradiation, as compared to control values (2.53 vs 1.36; 3.64 vs 1.36 nmol/109 blood platelets) and after the addition of MLT it decreased (2.53 vs 1.55; 3.64 vs 1.12 nmol/109 blood platelets). The activity of SOD-1 increased significantly compared to control values after 30 min. and 60 min. of exposure to EMR (1.97vs 0.75; 2.08 vs 0.75 U/g of protein), and significantly decreased after the addition of MLT only in samples exposed for 60 min. (2.08 vs 0.95 U/g of protein).
Discussion
The results demonstrated the possibly negative effect of EMR on oxygen metabolism of blood platelets and indicated a possible protective role of melatonin in this process.
Introduction. Bullous pemphigoid (BP) is one of the most common bullous diseases with an autoimmune background. The etiology and pathogenesis of BP are believed to be influenced not only by environmental, genetic, and immunological factors as well as by oxidative stress. BP is observed more frequently in elderly patients. Additionally, more potent oxidative stress is observed just in old age. Glutathione S-transferases (GSTs) play key roles in the detoxification of xenobiotics, metabolism of endogenous substrates, and the defense against oxidative stress. The present study examines whether polymorphism of genes encoding three selected GSTs (GSTM1, GSTT1, and GSTP1) might be associated with a higher risk for BP.
Materials and methods. The study involved 71 patients with BP and 100 healthy volunteers from a Polish population. The presence of the deletion type polymorphism for GSTM1 and GSTT1 was confirmed by multiplex PCR. The Ile105Val GSTP1 polymorphism was analyzed by PCR-RFLP.
Results. It was observed that the combination of GSTM1 null/GSTT1 null/GSTP1 Ile/Val, Val/Val genotypes occurred more frequently in patients with BP (8.5%) than in controls (4.0%). The odds ratio for carriers of GSTM1 null/GSTT1 null/ GSTP1 Ile/Val, Val/Val genotypes was 2.22 (95% CI 0.60–8.16; p = 0.3727), but was not statistically significant.
Conclusions. The combination of GSTM1 null, GSTT1 null, GSTP1 Ile/Val, Val/Val genotypes might be related to a greater risk of BP in a Polish population. However, future studies including more individuals are required to confirm this.
Glutaminolysis, beside glycolysis, is a key metabolic pathway of a cancer cell that provides energy and substrates for the synthesis of nucleic acids, proteins, and lipids. The pathway is mediated by both mitochondrial and cytosolic enzymes. Neither expression of glutaminolysis enzymes in colon cancer cells nor the influence of various oxygen concentrations on their expression has been studied so far.
Objectives
The aim of the study was to determine and compare the mRNA expression of enzymes involved in glutaminolysis at various oxygen levels in human primary (SW480) and metastatic (SW620) colon cancer cells cultured in 1% O2 (hypoxia), 10% O2 (tissue normoxia), 21% O2 (atmospheric normoxia).
Methods
Cell viability was determined by Trypan Blue exclusion (TB) and Thiazolyl Blue Tetrazolium Bromide (MTT). The expression of HIF1α, GLUT1, GLS1, AST1, AST2, ACL, PC and GC1, GC2 at mRNA levelwas determined by RT-qPCR. Results. Correlation between increasing oxygen concentration and cell count was not observed. In both cell lines the number of viable cells was the lowest at 10% oxygen. The enzyme profile and expression of proteins involved in glutaminolysis varied depending on oxygen pressure and type of cell lines. In summary, our findings suggest differences in metabolic adaptation to oxygen availability in vivo between primary and metastatic colon cancer cells.
Background. Langerhans cell histiocytosis is a rare reactive proliferative disorder marked by excess proliferation and accumulation of mononuclear phagocytes in tissues and organs. Usually, organs and systems where Langerhans cells are normally found are involved. Lesions may be limited to one system and be single- or multisite, or many systems may be involved. The etiology is not fully known. According to one of the hypotheses, immune dysfunction due to exuberant response to an unknown antigen may be the cause. The most common clinical symptoms include skin lesions, bone pain, exophthalmos, and enlarged lymph nodes, affecting the liver and spleen. Gingivitis, pocket granulation tissue, ulceration of the gingival papilla, alveolar bone atrophy leading to loosening and loss of teeth are observed in the oral cavity. The aim of the study was to determine the type and incidence of oral manifestations in patients diagnosed with Langerhans cell histiocytosis.
Methods. We evaluated patients’ medical records to obtain data on the children’s age at diagnosis, sex, the form of Langerhans cell histiocytosis, clinical picture (systemic and local oral symptoms), and radiological findings. Dental examinations (clinical and radiological) were performed to assess oral mucosa and periodontal tissues, and medical records were analyzed for the course and treatment of histiocytosis.
Results. The analysis included the medical records of 43 patients with Langerhans cell histiocytosis. Oral lesions in the form of gingivitis, pathological tooth mobility, and expansion of alveolar mandibular bone were observed in 7 patients. Conclusions. Langerhans cell histiocytosis may be accompanied by maxillary, gingival, and mucosal lesions.
The coexistence of depression and anxiety disorder significantly worsens the results of treatment and increases the risk of recurrent cardiovascular incidents.
The aim of the study was to assess the impact of cardiac rehabilitation on anxiety and depression symptoms in patients after interventional cardiology or coronary artery bypass graft (CABG).
Material and Methods
The study enrolled 40 participants aged 70.75±7.38 years, treated interventionally for ACS or undergoing urgent coronary artery bypass graft (CABG). Patients participated in 3-week stationary early cardiac rehabilitation. At the beginning and end of the study, the Beck Depression Inventory (BDI) and Spielberger’s State-Trait Anxiety Inventory (STAI) were performed.
Results
92.5% of subjects had at least one comorbidity, mostly hypertension (67.5%) and heart failure (60.0%). At the beginning the BDI level was 14.55±6.47; depression symptoms were present in 65% of subjects. At the end, BDI decreased significantly to 8.28±5.26; p<0.001. BDI was statistically significantly higher at the beginning and end in women than in men (17.94±7.07 vs. 11.78±4.40; p<0.05 and 10.56±5.90 vs. 6.41±3.88; p<0.01). Persons before rehabilitation were characterized by medium and low levels of STAI-X1 anxiety (31.80±7.24 and STAI-X2: 35.98±8.29). Finally, anxiety decreased statistically significantly to 26.40±6.30 and 29.80±6.57; p<0.001. At the beginning and end, it strongly correlated positively with the severity of depressive symptoms (STAI-X1 R=0.76; p<0.001, STAI-X2 R=0.70; p<0.001 and R=0.76; p<0.001, R=0.70; p<0.001).
Conclusions
Cardiac rehabilitation contributes significantly to reducing anxiety levels and reducing symptoms of depression. Implementation of these interventions as soon as possible brings the best results, contributing to reducing the risk of coronary events.
Introduction. Extended-spectrum β-lactamase (ESβL)-producing Klebsiella pneumoniae is currently one of the most common causes of nosocomial infections worldwide. The study aimed to characterize antibiotic resistance profile, the prevalence of selected genes encoding ESβLs, virulence, and the genetic relationship in 139 K. pneumoniae isolates identified in John Paul II Specialist Hospital in Southern Poland, collected in 2016.
Materials/Methods. Bacterial identification and the preliminary antibiotic susceptibilities was performed using the VI-TEK® 2 Compact automated system. Genes encoding ESβLs were amplified by CTX-Mplex PCR and PCR reactions. The presence of nine genes encoding virulence factors was studied by multiplex PCR. Clonality was investigated by PFGE after digestion with SpeI endonuclease.
Results. K. pneumoniae were mostly recovered from the respiratory tract (40.3%), urine (32.4%), wound swabs (19.4%) and blood (5%). In summary, 82.7% of strains were classified as multidrug resistant (MDR). All isolates were confirmed as ESβL producers and carried blaCTX-M-type (85.6%), blaSHV (82%), blaTEM (77.7%), blaCTX-M-9 (75.6%) and blaCTX-M-1 (1.4%) in various combinations. Moreover, triple bla genes were observed in 72% of isolates. The most common virulence-as-sociated genes found among the isolates were entB (91.4%), ybtS (55.4%), iutA (55.4%), magA (53.2%), kfu (14.4%), K2 (11.5%), mrkD (10.1%), rmpA (7.9%) and allS (5%). The PFGE analysis identified 4 major clusters (A–D) comprising 61% of the entire collection.
Conclusions. Our results indicate that the presence of a wide variety of MDR K. pneumoniae harbor ESβLs and virulence genes. Studies on molecular epidemiology of ESβL-producing K. pneumoniae isolates are needed, particularly for epidemiological surveillance in the hospital environment.
Pubblicato online: 17 Jan 2022 Pagine: 1005 - 1011
Astratto
Abstract
Introduction. Eclipse retinopathy occurs due to unprotected viewing of a solar eclipse. It is a long-recognized condition. The damage inflicted to the macula is due to a photochemical and photothermal effect caused by sunlight that enters the eye and is focused by the crystalline lens. Animal studies into eclipse retinopathy have been previously carried out. Retinal irradiance levels leading to macular damage have been established in rabbits. Limited data from studies on primates are also available. However, the exact values for humans have not yet been established with confidence.
Methods. Here we present a simple method for estimation of the retinal irradiance dose in humans and a classification of macular damage.
Results. As an example, the retinal irradiance dose of a theoretical patient observing the solar eclipse of March 20, 2015, is given along with the grade of macular damage according to the developed classification.
Discussion. The retinal irradiance values given in the classification are provisional for the time being. With more widespread use among ophthalmologists the developed classification should become useful for prognostic purposes.
Pubblicato online: 30 Dec 2021 Pagine: 1012 - 1019
Astratto
Abstract
Patients on maintenance hemodialysis are a group with high cardiovascular risk, characterized by high arterial stiffness, which is considered a novel cardiovascular risk factor. Diabetes mellitus is both one of the leading causes of end-stage renal disease and a determinant of poor outcome in this group. The aim of the study was to examine carotid stiffness with high resolution echo-tracking in order to assess the influence of diabetes mellitus on arterial stiffness in this group.
Ninety patients (47 F; 43 M) with end-stage renal disease on maintenance hemodialysis were divided into two subgroups: diabetic and nondiabetic (37 and 53 patients respectively). They underwent clinical examination, laboratory tests, and ultrasonographic carotid stiffness assessment both before and after hemodialysis. Local arterial stiffness parameters β, Ep, AC, and PWVβ were calculated. Patient survival was assessed after a 58-month-long follow-up. During the 58-month period 25 of these diabetic patients died, as did 18 non-diabetic patients. Diabetes mellitus was a risk factor for overall mortality among the group of hemodialysed patients. Patients who died from non-cardiovascular causes significantly more often suffered from diabetes mellitus than survivors. There were no statistically significant differences in local arterial stiffness between the groups.
Local arterial stiffness in hemodialysed patients, assessed with high resolution echo-tracking, is not influenced by the presence of diabetes.